MEraCAL .SCHOOL Digitized by tine Internet Arcinive in 2007 with funding from Microsoft Corporation http;//www.arcliive.org/details/develoliumanb6dy00mcmuricli THE DEVELOPMENT OF THE HUMAN BODY MCMURRICH MORRIS'S ANATOMY FIFTH EDITION UNDER AMERICAN EDITORSHIP Rewritten, Revised, Improved, with Many New Illustralions EDITED BY C. M. JACKSON, M. S., M. D. Professor and Director of the Department of Anatomy University of Minnesota Among the American contributors will be noted: C. M. Jackson, J. Playfair McMurrich, R. J. Terry, Irving Hardesty, Abram T. Kerr, Charles R. Bardeen, Eliot R. Clark, and H. D. Senior. F. W. Jones, John Morley, Peter Thomson, David Waterston head the English contributors. "The ever-growing popularity of the book with teachers and students is an index of its value, and it may safely be recommended to all interested." — From The Medical Record, New York. The text has been completely revised. Very special attention, in this new edition, has been paid to the illustrations, with the result that the teaching value of the book has been materially increased. It contains many features of special advantage to students. It is modern, up to date in every respect. It has been carefully revised, and in many parts rewritten, and includes many new features. Containing 1182 Illustrations, of which 358 are in colors. One Handsome Octavo Volume. Thumb Index. Cloth, $9.00. Or in Five Parts, as follows, each part sold separately: PART I.— Morphogenesis. Osteology.' Articulations. Index. $2.25. PART II.— Muscles. Blood— vascular System; Lymphatic System. $3.25. Part III.— Nervous System. Special Sense Organs. Index. $3.00. PART IV.— Organs of Digestion; of Voice and Respiration. Urinary and Repro- ductive Organs. Ductless Glands. Skin and Mammary Glands. Index. $2.25. PART v.— Clinical and Topographical .A.natomy. Index. $2.25. THE DEVELOPMENT OF THE HUMAN BODY A MANUAL OF HUMAN EMBRYOLOGY J. PLAYFAIR iyicMURRICH, A. M., Ph. D., LL. D. PROFESSOR OF ANATOMY IN THE UNIVERSITY OF TORONTO FORMERLY PROFESSOR OF ANATOMY IN THE UNIVERSITY OF MICHIGAN SIXTH EDITION, REVISED AND ENLARGED With Two Hundred and Ninety Illustrations Several of which are Printed in Colors PHiLADiLf^HlA P. RLA)CLSTON'S SON & CO ^ ^ ^ ; ibii Walnut 31 REET Copyright, 1920, by P. Blakiston's Son & Co. •1: ; ,'•'». ' \ '^i/'. •, tx'b'm'apVx •VBagV«';v'<}s|c; p^ / 9^0 PREFACE TO THE SIXTH EDITION The increasing interest in human and mammalian embryology which has characterized the last few years has resulted in many additions to our knowledge of these branches of science, and has necessitated not a few corrections of ideas formerly held. In this sixth edition of this book, as in previous ones, the attempt has been made to incorporate the results of all important recent contri- butions upon the topics discussed, and. at the same time, to avoid any considerable increase in the bulk of the volume. Several chapters have, therefore, been largely recast, and the subject matter has been thoroughly revised throughout, so that it is hoped that the book forms an accurate statement of our present knowledge of the development of the human body. In addition to the works mentioned in the preface to the first edition as of special value to the student of Embryology, mention should be made of the Handhuch der vergleichenden und experimen- tellen Entwicklungslehre der Wirheltiere edited by Professor Oscar Hertwig and especially of the Manual of Human Embryology edited by Professors F. Keibel and F. P. Mall. University of Toronto. 81158 PREFACE TO THE FIRST EDIIION The assimilation of the enormous mass of facts which consti- tute what is usually known as descriptive anatomy has always been a difficult task for the student. Part of the difficulty has been due to a lack of information regarding the causes which have determined the structure and relations of the parts of the body, for without some knowledge of the why things are so, the facts of anatomy stand as so many isolated items, while with such knowl- edge they become bound together to a continuous whole and their study assumes the dignity, of a science. The great key to the significance of the structure and relations of organs is their development, recognizing by that term the historical as well as the individual development, and the following pages constitute an attempt to present a concise statement of the development of the human body and a foundation for the proper understanding of the facts of anatomy. Naturally, the individual development claims the major share of attention, since its pro- cesses are the more immediate forces at work in determining the conditions in the adult, but where the embryological record fails to afford the required data, whether from its actual imperfection or from the incompleteness of our knowledge concerning it, recourse has been had to the facts of comparative anatomy as affording indications of the historical development or evolution of the parts under consideration. It has not seemed feasible to include in the book a complete list of the authorities consulted in its preparation. The short bibliographies appended to each chapter make no pretensions to completeness, but are merely indications of some of the more important works, especially those of recent date, which con- sider the questions discussed. For a very full bibliography of all works treating of human embryology up to 1893 reference vii Vlll PREFACE TO THE FIRST EDITION may be made to Minot's Bibliography of Vertebrate Embryology, published in the "Memoirs of the Boston Society of Natural History," volume iv, 1893. It is fitting, however, to acknowledge an especial indebtedness, shared by all writers on human embryology, to the classic papers of His, chief among which is his Anatomie menschlicher Embryonen, and grateful acknowledge- ments are also due to the admirable text-books of Minot, O. Hertwig, and Kollmann. Anatomical Laboratory, University of Michigan. CONTENTS Paob rXRODUCTION I PART I.— GENERAL DEVELOPMENT CHAPTER I The Spermatozoon and Spermatogenesis; the Ovum and Its Matu- ration and Fertilization ii CHAPTER II The Segmentation of the Ovum and the Formation of the Germ Layers 41 CHAPTER III The Medullary Groove, Notochord, and Mesodermic Somites . . 67 CHAPTER IV The Development of the External Form of the Human Embryo .89 CHAPTER V The Yolk-stalk, Belly-stalk, and Fetal Membranes no PART II.— ORGANOGENY CHAPTER VI The Development of the Integumentary System 143 CHAPTER VII The Development of the Connective Tissues and Skeleton . . . 155 CHAPTER VIII The Development of the Muscular System 195 is X CONTENTS CHAPTER IX The Development of the Circulatory and Lymphatic Systems. . 222 CHAPTER X The Development of the Digestive Tract and Glands 282 CHAPTER XI The Development of the Pericardium, the Pleuro-peritoneum, and the Diaphragm 3^9 CHAPTER XII The Development of the Organs of Respiration 334 CHAPTER XIII The Development of the Urinogenital System 341 CHAPTER XIV The Suprarenal System of Organs 374 CHAPTER XV The Development of the Nervous System 381 CHAPTER XVI The Development of the Organs of Special Sense 432 CHAPTER XVII Post-natal Development 475 Index 491 THE DEVELOPMENT OF THE HUMAN BODY INTRODUCTION One of the fundamental principles of biology is that which regards all organisms as composed of one or more structural units, termed cells. Each of these maintains an individual existence and in multicellular organism is influenced by its fellows and contri- butes with them to the maintenance of the general existence of the individual of which it is a part. This is the cell theory formulated by Schleiden and Schwann (1839), and according'to it the human body, though physiologically a unit, is, structurally, a community, an aggregate of many individual units, each of which leads to a certain extent an independent existence and yet both contributes to and shares in the general welfare of the community. To the founders of the theory the structural units were vesicles with definite walls, and little attention was paid to their contents. Hence the use of the term "cell" in connection with them. Long before the establishment of the cell theory, however, the existence of organisms composed of a gelatinous substance showing no indi- cations of a definite limiting membrane had been noted, and in 5 a French naturalist, Dujardin, had described the gelatinous material of which certain marine organisms (Rhizopoda) are composed, terming it sarcode and maintaining it to be the material substratum which conditioned the various vital phenomena exhib- Kd by the organisms. Later, in 1846, a botanist, von Mohl, 2 INTRODUCTION observed that living plant cells contained a similar substance, upon which he believed the existence of the cell as a vital structure was dependent, and he bestowed upon this substance the name proto- plasm, by which it is now universally known. By these discoveries the importance originally attributed to the cell- wall was greatly lessened, and in 1864 Max Schultze reformu- lated the cell theory, defining the cell as a mass of protoplasm, the presence or absence of a limiting membrane or cell-wall being im- material. At the same time the spontaneous origination of cells from an undifferentiated matrix, believed to occur by the older authors, was shown to have no existence, every cell originating by the division of a preexisting cell, a fact concisely expressed in the aphorism of Virchow — omnis cellula a celluld. Interpreted in the light of these results, the human body is an aggregate of myriads of cells* — i.e., of masses of protoplasm, each of which owes its origin to the division of a preexistent cell and all of which may be traced back to a single parent cell — a fertilized ovum. All these cells are not alike, however, but just as in a social community one group of individuals devotes itself to the performance of one of the duties requisite to the well-being of the community and another group devotes itself to the perform- ance of another duty, so too, in the body, one group of cells takes upon itself one special function and another another. There is, in other words, in the cell-community a physiological division of labor. Thus certain cells become especially contractile, forrring muscle cells; others become especially irritable, responding readily to stimulation, and form nerve cells; others undertake the forma- tion of this or that secretion useful to the organism as a whole and are gland cells ; while others set themselves apart for the reproduc- tion of the species. Each functional specialization is associated with a more or less definite structural adaptation, so that the general function of a cell may be recognized from its form and structure. The comparison of the cell-community to the social * It has been estimated that the number of cells entering into the composition of the body of an adult human being is about twenty-six million five hundred thousand millions. INTRODUCTION 3 community may thus be carried still further, for just as gradations of individuality maybe recognized in the individual, the municipal- ity, and the state, so too in the cell-community there are cells; tissues, each of which is an aggregate of similar cells; organs^ which are aggregates of tissues, one, however, predominating and determining the character of the organ; and systems, which are aggregates of organs having correlated functions. It is the province of embryology to study the mode of division of the fertilized ovum and the progressive differentiation of the re- sulting cells to form the tissues, organs, and systems. But before considering these phenomena as seen in the human body it will be well to get some general idea of the structure of an animal cell. This as has been already stated, is a mass of protoplasm, but, as a rule, one finds imbedded in this various products of its activi- ties, such as globules of fat, pigment, or secretion granules, all of which may be grouped together as deutoplasm (Fig. i). The protoplasm itself is a viscous substance resembling egg-albumen in many of its physical peculiarities and like this being coagulated by heat or when it is exposed to the action of various chemical reagents. It is to be regarded as a colloidal mixture, whose principal constituents are albuminous and lipoid susbtances in varying proportions, the term protoplasm not connoting any defi- nite chemical compound, but being rather a morphological con- cept denoting all those colloidal complexes whose activities result in the manifestation of the phenomena which we term Life. The protoplasm of an animal cell is, however, by no means a homogeneous material. Even in the living cell what is termed a nucleus (Fig. i. A'') is usually clearly discernible as a more or less spherical body of a greater refractive index than the surround- ing protoplasm, and since this is a permanent organ of the cell it is convenient to distinguish . the surrounding protoplasm as cyto- plasm from the nuclear protoplasm or karyo plasm. But the structure of the nucleus and other organs of the cell can be more accurately determined when the protoplasm has been ''fixed" or coagulated by certain reagents and then subjected to the action of dyes which have a selective affinity for the various struc- 4 INTRODUCTION tural constituents. Treated thus both cytoplasm and karyoplasm present the appearance of a more solid reticulum forming a net- work in whose meshes is a more fluid material, the enchylema. At the surface of the cell the cytoplasmic reticulum passes over in o a more homogeneous layer, which may be distinguished even in the living cell by its greater firmness and resistence as compared with the more fluid central material. This surface pellicle is termed the ectoplasm (Fig. i , Ect) as distinguished from the central endoplasm {End) and there is a similar pellicle enclosing the karyoplasm. Pig. I. — Diagram Showing the Structure of a Cell. Ar, Archoplasm Sphere; cho, Chondriosome; chr. Chromatin; Dp, Deutoplasm; Ect, Ecto- plasm; End, Endoplasm; N, Nucleus; n. Nucleolus. forming the nuclear membrane. In addition to the reticulum and enchylema the karyoplasm has scattered along the fibres of its reticulum a peculiar material termed chromatin and usually con- tains, embedded in its substance , one or more spherical bodies termed nucleoli, which may be merely larger masses of chromatin or bodies of special chemical composition. Further, in all actively growing cells there is differentiated in the cytoplasm a peculiar body known as the archoplasm sphere (Fig. i, Ar), in the center of which there is usually a minute spherical body, known as the centrosome, these structures playing an important part in the repro- duction of the cell by division. Finally there are also present INTRODUCTION 5 in the cytoplasm structures termed chondriosomes (Fig. i, Cho) which have the form of minute granules, mitochondria, or rods, chondrioconts, and have been supposed by some observers to be^ concerned with the formation of special products of the cytoplasm, such as neurofibrils, secretion products, etc. It has been already stated that new cells arise by the division of preexisting ones, and this process is associated with a series of com- plicated phenomena which have great significance in connection with some of the problems of embryology. When such a cell as has been described above is about to divide, the fibers of the reticulum in the neighborhood of the archoplasm sphere arrange themselves so as to form fibrils radiating in all directions from the sphere as a center, and the archoplasm with its contained centro- some gradually elongates and finally divides, each portion retain- ing its share of the radiating fibrils, so that two asters, as the aggre- gate of centrosome, sphere and fibrils is termed, are now to be found in the cytoplasm (Fig. 2, A). Gradually the two asters separate from one another and eventually come to rest at opposite sides of the nucleus (Fig. 2, C). In this structure important changes have been taking place in the meantime. The nuclear membrane disappears and the chromatin, originally scattered irregularly along the reticulum, gradually aggregates to form a continuous thread (Fig. 2, A) and later this thread breaks up into a definite number of pieces, termed chromosomes (Fig. 2, B), the number of these being practically constant for each species of animal. The number occurring in man is probably twenty-four (Flemming, Duesberg, Wieman). As soon as the asters have taken up their position on opposite sides of the nucleus, the nuclear reticulum begins to be converted into a spindle-shaped bundle of fibrils which associate themselves with the astral rays and have lying scattered among them the chromosomes (Fig. 2, C). To the figure so formed the term amphiaster is applied, and soon after its formation the chromo- somes arrange themselves in a circle or plane at the equator of the spindle (Fig. 2, D) and the stages preparatory to the actual division, the prophases, are completed. INTRODUCTION The next stage, the metaphase (Fig. 3, ^), consists of the divi- sion, usually longitudinally, of each chromosome, so that the cell now contains twice as many chromosomes as it did previously. As soon as this division is completed the anaphases are inaugurated by the halves of each chromosome separating from one another and approaching one of the asters (Fig. 3, B), and a group of chromo- FlG. 2. -Diagrams Illustrating the Prophases of Mitosis. — (Adapted from E. B. Wilson.) somes, containing half the total number formed in the metaphase, comes to lie in close proximity to each archoplasm sphere (Fig. 3, C). The spindle and astral fibers gradually resolve themselves again into the reticulum and the chromosomes of each group become irregular in shape and gradually spread out upon the nuclear reticulum so that two nuclei, each similar to the one from INTRODUCTION which the process started, are formed (Fig. 3, Z)). Before all these changes are accomplished, however, a constriction makes its appearance at the surface of the cytoplasm (Fig. 3, C) and, gradually def^pening, divides the cytoplasm in a plane passing through the equator of the amphiaster and gives rise to two separate cells (Fig. 3, Z>). Fig. 3. — Diagrams Illustrating the Metaphase and Anaphases of Mitosis. — ^Adapted from E. B. Wilson.) This complicated process, which is known as karyokinesis or mitosis, is the one usually observed in dividing cells, but occasion- ally a cell divides by the nucleus becoming constricted and divid- ing into two parts without any development of chromosomes, spindle, etc., the division of the cell following that of the nucleus.^ This amitotic method of division is, however, rare, and in many 8 INTRODUCTION cases, though not always, its occurrence seems to be associated with an impairment of the reproductive activities of the cells. In actively reproducing cells the mitotic method of division may be regarded as the rule. Since the process of development consists of the multiplication of a single original cell and the differentiation of the cell aggregate so formed, it follows that the starting-point of each line of indi- vidual development is to be found in a cell which forms part of an individual of the preceding generation. In other words, each in- dividual represents one generation in esse and the succeeding gene- ration in posse. This idea may perhaps be made clear by the following considerations. As a result of the division of a fertilized ovum there is produced an aggregate of cells, which, by the physio- logical division of labor, specialize themselves for various func- tions. Some assume the duty of perpetuating the species and are known as the sexual or germ cells, while the remaining ones divide among themselves the various functions necessary for the main- tenance of the individual, and may be termed the somatic cells. The germ cells represent potentially the next generation, while the somatic cells constitute the present one. The idea may be represented schematically thus: First generation Somatic cells -\- germ cells ' II Second generation Soiiiatic cells -f- germ cells II Third generation Somatic cells + germ cells, etc. It is evident, then, while the somatic cells of each generation die at their appointed time and are differentiated anew for each gene- ration from the germ cells, the latter, which may be termed collec- tively the germ-plasm, are handed on from generation to generation without interruption, and it may be supposed that this has been INTRODUCTION 9 the case ab initio. This is the doctrine of the continuity of the germplasm, a doctrine of fundamental importance on account of its bearings on the phenomena of heredity. It is necessary, however, to fix upon some link in the continuous chain of the germ-plasm as the starting-point of the development of each individual, and this link is the fertilized ovum. By this is meant a germ cell produced by the fusion of two units of the germ- plasm. In many of the lower forms of life (e.g. Hydra and certain turbellarian worms) reproduction may be accomplished by a di- vision of the entire organism into two parts or by the separation of a portion of the body from the parent individual. Such a method of reproduction is termed non-sexual. Furthermore in a number of forms {e.g., bees, Phylloxera, water-fleas) the germ cells are able to undergo development without previously being fertilized, this con- stituting a method of reproduction known as parthenogenesis. But in all these cases sexual reproduction also occurs, and in all the more highly organized animals it is the only niethod that normally occurs; in it a germ cell develops only after complete fusion with another germ cell. In the simpler forms of this process little difference exists between the two combining cells, but since it is, as a rule, of advantage that a certain amount of nutrition should be stored up in the germ cells for the support of the developing embryo until it is able to secure food for itself, while at the same time it is also advantageous that the cells which unite shall come from differ- ent individuals (cross-fertilization), and hence that the cells should retain their motility, a division of labor has resulted. Certain germ cells store up more or less food yolk, their motility becoming thereby impaired, and form what are termed the female cells or ova, while others discard all pretensions of storing up nutri- tion, are especially motile and can seek and penetrate the inert ova; these latter cells constitute the male cells or spermatozoa. In many animals both kinds of cells are produced by the same indi- vidual, but in all the vertebrates (with rare exceptions in some of the lower orders) each individual produces only ova or spermato- zoa, or, as it is generally stated, the sexes are distinct. It is of importance, then, that the peculiarities of the two lO INTRODUCTION forms of germ cells, as they occur in the human species, should be considered. LITERATURE R. Chambers: "Microdissection Studies." Amer. Jour. Physiol., xliii, 1917, and Jour. Exper. ZooL, xxiii, 191 7. E. V. Cowdry: "The general functional significance of mitochondria" Amer. Jour. Anat., xix, 1916. J. Duesberg: " Plastosomen, Apparato reticolare interno, und Chromidial- apparat," Ergeb. Anat. u. Emtw., xx, 191 1. J. Duesberg: "On the Present Status of the Chondriosome Problem." Biol. Bully xxxvi, 1919. O. Hertwig: "Die Zelle und die Gewebe." Jena, 1893. H. L. WiEMAN: "Chromosomes in Man" Amer. Jour. Anat., xiv, 19 13. E. B. Wilson: "The Cell in Development and Inheritance." Third edition New York, 1900. PART I GENERAL DEVELOPMENT CHAPTER I THE SPERMATOZOON AND SPERMATOGENESIS; THE OVUM AND ITS MATURATION AND FERTILIZATION The Spermatozoon. — The human spermatozoon (Figs. 4 and 5) is a minute and greatly elongated cell, measuring about 0.05 mm. in length. It consists of an anterior broader portion or head (Fig. S,H), which measures about 0.005 ^i^- '^^ length and, when viewed from one surface (Fig. 4, i), has an oval outline, though since it is somewhat flattened or concave toward the tip, it has a pyriform shape when seen in profile (Fig. 4, 2). Covering the flattened portion of the head and fitting closely to it is a delicate cap-like membrane, the head-cap (Fig. 5, H.C.), whose apex is a sharp edge, this structure corresponding to a pointed prolongation of the cap found in the spermatozoon of many of the lower vertebrates and known as the perforatorium. Immediately behind the head is a short portion known as the neck (Fig. 5, iV), which consists of an upper more refractive body, the anterior nodule, and a lower clearer portion. To this succeeds the connecting or middle-piece (Figs. 4, m and 5, M) which begins with a posterior nodule, from the center of which there passes back through the axis of the piece an axial filament, enclosed within a sheath, this latter having wrapped around it a spiral filament. At the lower end of the middle piece this spiral filament terminates in the annulus, through which the axial filament and its sheath passes into the flagellum or tail (Fig. 4, /). This portion, which constitutes about four-fifths II 12 THE SPERMATOZOON of the total length of the spermatozoon is composed 'simply of the axial filament and its sheath, this latter gradually thinning out as it passes backward and ceasing altogether a short distance above the end of the axial filament. The filament thus projects some- k \m Fig. 4. — Human Spermatozoon. I, Front view; 2, side view of the head; e, terminal filament; k, head; /, tail; m, middle-piece. —{After Retzius.) H. { N. M. Fig. 5. — Diagram Showing tIie Structure OF A Human Spermatozoon. Af, Axial filament; An, annulus; H, head; H. C, lower border of head-cap; M, middle - piece; N, neck; Na and Np, anterior and pos- terior nodule; S, sheath of axial filament; Spf, spiral filament. — {Bonnet, after Meves.) what beyond the actual end of the tail, forming what is known as • the terminal filament or end-piece (Fig. 4, e) . To understand the significance of the various parts entering into the composition of the spermatozoon a study of their develop- ment is necessary, and since the various processes of spermatogene- sis have been much more accurately observed in such mammalia as the rat and guinea-pig than in man, the description which follows will be based on what has been described as occurring in these forms. From what is known of the spermatogenesis in man it SPERMATOGENESIS 13 seems certain that it closely resembles that of these mammals so far as its essential features are concerned. Spermatogenesis. — ^The spermatozoa are developed from the cells which line the interior of the seminiferous tubules of the testis. The various stages of development cannot all be seen at any one part of a tubule, but the formation of the spermatozoa seems to sc^:^ sg- Fig. 6. — Diagram Showing Stages gf Spermatogenesis as Seen in Differ- ent Sections of a Seminiferos Tubule of a Rat. sc^, spermatocyte of the first order; sc^, spermatocyte of the second order; sg, spermatogonium; sp, spermatid; sz, spermatozoon, pled. — (Adapted from Lenhossek.) The Sertoli cells are stip- pass along each tubule in a wave-like manner and the appearances presented at different points of the wave may be represented dia- grammatically as in Fig. 6. 14 SPERMATOGENESIS In section A of this figure four different generations of cells are represented; above are mature spermatozoa lying in the lumen of the tubule, while next the basement membrane is a series of cells from which a new generation of spermatozoa is about to develop. The cells of this series are of two kinds; the stippled one will develop into a structure known as a Sertoli cell, while the others , termed spermatogonia (sg) , are the parent cells of both spermatozoa and Sertoli cells. The spermatogonia undergo several divisions before becoming the actual parent cells of the structures men- tioned, and it is found that about one in four of the ultimate sper- matogonia contains a peculiar rod-like crystalloid, the crystalloid of Lubarsch. It seems probable that the cells possessing these structures are the parent cells of the Sertoli cells. For the latter also contain crystalloids, these being of two kinds, a large one, the crystalloid of Charcot, and one or two smaller ones, similar to the Lubarsch crystalloids of the parent cells. It is supposed that both kinds of crystalloids have been formed by the division of a Lubarsch crystalloid during the growth of the Sertoli cell. This growth is very rapid, the cells increasing greatly in size, as is indi- cated in Fig. 6, and branching at their free ends to ramify around groups of sperm-cells, each Sertoli cell thus coming to enclose at its free end twenty-four spermatozoa, to which it acts as a nurse, supplying them with nutrition. The spermatozoa when mature are set free in the lumen of the seminiferous tubule and their Sertoli cell then degenerates. Sertoli cells, therefore, continue to be formed throughout the period of sexual activity, new ones for each generation of spermatozoa being formed from the spermatogonia. Those ultimate spermatogonia that do not contain crystalloids are the parent cells of the spermatozoa and each divides into two cells termed primary spermatocytes, indicated in sections A and B of Fig. 6 by sc^. In the section C these cells are shown dividing to form secondary spermatocytes (sc"^), and these almost imme- diately divide again, each giving rise to two spermatids {sp), which later become directly transformed into spermatozoa. From each primary spermatocyte there are formed, therefore, as the SPERMATOGENESIS 15 result of two mitoses, four cells, each of which represents a spermatozoon. During these divisions important departures from the typical method of mitosis occur, these departures leading to a reduction of the chromosomes in each spermatid to one-half the number occurring in the somatic cells. The general plan by which this is Pig. 7. — Diagram Illustrating the Reduction of the Chromosomes During Spermatogenesis. 5c^ Spermatocyte of the first order; sc^, spermatocyte of the second order; sp, spermatid. accomplished may be described as follows: In the division of the spermatogonia the number of chromosomes that appears is iden- tical with that found in the somatic cells, so that in a form whose somatic number is eight, eight chromosomes appear in each spermatogonium, and divide so that eight pass to each of the resulting primary spermatocytes. When these cells divide, how- 1 6 SPERMATOGENESIS ever, the number of chromosomes that appears is only one-half the somatic number, namely, four in the supposed case that is being described (Fig. 7, sc^). The further history of these chromosomes indicates that each is composed of four elements more or less closely united to form a tetrad, and during mitosis each tetrad divides into two dyads, four of which will therefore pass into each secondary spermatocyte. These cells (Fig. 7 , sc"^) finally undergo a division in which each of the dyads they contain is halved, so that each sper- matid receives a number of single chromosomes equal to half the number characteristic for the species (Fig. 7, sp). This account of the behavior of the chromosomes during spermatogenesis assumes that all the chromosomes of the primary spermatocytes are of equal value and behave simil- arly during mitosis. It has been found, however, that in a number of forms (insects, spiders, birds, mammals, etc.) this is not the case and it seems probable that in man also certain of the spermatocytic chromosomes, termed idiochromosomes, differ decidedly from their fellows. The exact behavior of these special chromosomes is still somewhat uncertain so far as the human species is concerned, but according to the recent observations of Wieman it is as follows. In the spermatogonial divisions twenty-four chromosomes appear, two of which are idiosomes and for convenience may be denoted as X and Y. In the primary spermatocyte only twelve chromo- somes appear, one of which is the now paired XY element, and in the metaphase this element divides longitudinally, one-half passing to each pole of the mitotic spindle (Fig. 8, XY^ and XY^) . In the secondary spermatocyte twelve chromosomes again appear and in the metaphase all divide, the X idiochromosome separating from the Y and passing to the opposite spindle pole. Each sper- matid thus contains eleven ordinary chromosomes, but in addi- tion half of them contain an X idiochromosome, while the other half contain a Y idiochromosome (Fig. 8). Guyer and Montgomery have, however, obtained quite differ- ent results. According to the former the two idiochromosomes do SPERMATOGENESIS 17 not divide in the primary spermatocyte division, but pass un- changed to one pole of the spindle, so that half the secondary spermatocytes contain idiochromosomes and the other half do not. Since all the chromosomes of the secondary spermatocyte divide there will thus be two classes of spermatids, one possessing ten ordinary chromosomes and the other possessing these plus Fig. 8. — Diagram Illustrating Human Spermatogenesis. The upper figure represents a metaphase in the primary spermatocyte it which 1 1 ordinary chromosomes from the equatorial plate, the xy element having already divided the daughter elements passing to opposite poles. The middle figures repre- sent the equatorial plates of two secondary spermatocytes each consisting of 11 ordinary chromosomes and an xy element. TJie lower figures show the chromo- some constituents of the spermatids, each comaining n ordinary chromosomes, but half of them with an x element and a half with a y element. — {Based on Wietnan.) two idiochromosomes. Montgomery on the other hand believed that there was a good deal of variety in the behavior of the idiochromosomes and held that there were at least four, and possi- l8 SPERMATOGENESIS bly five or six, classes of spermatids, and the matter is further complicated by the results obtained by von Winiwarter, according to which the primary spermatocytes possessed twenty-four chro- mosomes instead of twelve. One of these twenty-four was an idiochromosome, which on division passed undivided into one of the secondary spermatocytes, so that of these cells there were two classes, one containing twenty-four chromosomes and the other twenty-three, and this condition was transmitted to the sper- matids. These very divergent results are greatly in need of thorough revision, but one feature is common to all in that two classes of spermatids are recognized, differing in their chromosomal constituents. The significance of this will be considered later (P- 32). The transformation of the spermatids into spermatozoa takes place while they are in intimate association with the Sertoli cells, a number of them fusing with the cytoplasm of an enlarged Sertoli cell, as shown in Fig. 6, s, and probably receiving nutrition from it. In each spermatid there is present in addition to the nucleus, an archoplasm sphere, two centrosomes that have migrated from the archoplasm and lie free in the cytoplasm, and numerous chondriosomes. The centrosomes and the archoplasm sphere take up their position at opposite poles of the nucleus, the archo- plasm eventually forming the head-cap of the spermatozoon, and from one of the centrosomes a slender axial filament grows out and soon projects beyond the limits of the cytoplasm (Fig. g, A). The other centrosome becomes a rod-shaped structure which ap- plies itself closely to the posterior pole of the nucleus, becoming the anterior nodule, while the lower one, from which the filament arises becomes at first pyramidal in shape (Fig. 9, B) and later separates into a rod-like portion to which the filament is attached and a ring, through which the filameAt passes (Fig. 9, C). The rod-like portion becomes the posterior nodule, and the ring separates from it to form the annulus (Fig. 9, D). The nucleus becomes the head of^the spermatozoon, the cytoplasm surrounding it becoming reduced to an exceedingly delicate layer, so that the head is com- posed almost entirely of nuclear substance, if the head-cap be left THE OVUM 19 out of consideration. The spiral filament of the middle-piece is, however, formed from the cytoplasmic chondrosomes, and according to some authors these also furnish the material for the sheath of the axial filament, though this has been denied (Meves)7 the sheath being regarded a differentiation of the axial filament. Each spermatozoon is, then, one of four equivalent cells, produced by two successive divisions of a primary spermatocyte and con- taining approximately one-half the number of chromosomes characteristic for the species. Fig. 9. -Stages in the Transformation of a Spermatid into a Spermatozoon. — (After Meves.) The number of spermatozoa produced during the lifetime of a single individual is very large. It has been found that i cu. mm. of human ejaculate contains 60,876 spermatozoa, a single ejaculate, therefore, containing over 200,000,000. This would indicate that during his lifetime a man may produce 340 billion spermatozoa (Lode). The Ovum. — The human ovum is a spherical cell measuring about 0.2 mm. in diameter and is contained within a cavity situ- ated near or at the surface of the ovary and termed a Graafian follicle. This follicle is surrounded by a capsule composed of two layers, an outer one, the theca externa, consisting of fibrous tissue resembling that found in the ovarian stroma, and an inner one, the theca interna, composed of numerous spherical and fusiform cells. 20 THE OVUM Both the thecae are richly supplied with blood-vessels, the theca interna especially being the seat of a very rich capillary network. Internal to the theca interna there is a transparent, thin, and structureless hyaline membrane, within which is the follicle proper, whose wall is formed by a layer of cells termed the stratum granu- losum (Fig. lo, mg) which inclose a cavity filled with an albuminous fluid, the liquor folliculi. At one point, usually on the surface Pig. 10. — Section through Portion of an Ovary of an Opossum (Didephys vir- giniana) showing Ova and Follicles in Various Stages of Development. b. Blood-vessel; dp, discus proligerus; mg, stratum granulosum; o, ovum; s, stroma; th, theca folliculi. nearest the center of the ovary, the stratum granulosum is greatly thickened to form a mass of cells, the discus proligerus (dp), which projects into the cavity of the follicle and encloses the ovum (a). Usually but a single ovum is contained in any discus, though occasionally two or even three may occur. The cells of the discus proligerus are for the most part more or less spherical or ovoid in shape and are arranged irregularly. In THE OVUM 21 the immediate vicinity of the ovum, however, they are more co- lumnar in form and are arranged in about two concentric rows, thus giving a somewhat radiated appearance to this portion of the dis-_ cus, which is termed the corona radiata (Fig. 1 1, cr). Immediately within the corona is a transparent membrane, the Zona pellucida (Fig. II, Zp), about as thick as one of the cell rows of the corona (0.02 to 0.024 mm.), and presenting a very fine radial striation zp Fig. II. — Ovum from Ovary of a Woman Thirty Years of Age. cr. Corona radiata; n, nucleus; p, protoplasmic zone of ovum; ps, perivitelline space; y, yolk; zp, zona pellucida. — (Nagel.) which has been held to be due to minute pores traversing the mem- brane and containing delicate prolongations of the cells of the corona radiata. Within the zona pellucida is the ovum proper, whose cytoplasm is more or less clearly differentiated into an outer more purely protoplasmic portion (Fig. 11, p) and an inner mass (y) which contains numerous fine granules of fatty and albuminous natures. These granules represent the food yolk or deutoplasm, 2 2 OVULATION AND THE CORPUS LUTEUM which is usually much more abundant in the ova of other mammals and forms a mass of relatively enormous size in the ova of birds and reptiles. The nucleus (n) is situated somewhat excentrically in the deutoplasmic portion of the ovum and contains a single, well-defined nucleolus. A folHcle with the structure described above and containing a fully grown ovum may measure anywhere from five to twelve millimeters in diameter, and is said to be ^'mature/'having reached its full development and being ready to burst and set free the ovum. This, however, is not yet mature; it is not ready for fer- tilization, but must first undergo certain changes similar to those through which the spermatocyte passes, the so-called ovum at this stage being more properly a primary oocyte. But before describing the phenorrena of maturation of the ovum it will be well to consider the extrusion of the ovum and changes which the follicle subsequently undergoes. Ovulation and the Corpus Luteum. — As a rule, but a single follicle near maturity is found in either the one or the other ovary at any given time. In the early stages of its develop- ment a follicle is situated somewhat deeply in the stroma of the ovary, but as the liquor folliculi increases in amount a tension is produced within the follicle which causes it to en- large especially in the direction of least resistance, that is to- pic i2.-0vary OF A Woman Nine- ^^rds the surface of the ovary, TEEN Years of Age, Eight Days after -^ Menstruation. where it eventually forms a d. Blood-clot; /, Graafian follicle; th, marked prominence and its con- theca. — {Kollmann.) tents are separated from the ab- dominal cavity only by an exceedingly thin membrane. This membrane finally ruptures, and the liquor folliculi rushes out through the rupture, carrying with it the ovum surrounded by some of the cells of the discus prohgerus. OVULATION AND THE CORPUS LUTEUM 25 The immediate cause of the bursting of the follicle has usually been ascribed to the tension within the follicle, due to the increase of the liquor folliculi, finally reaching the bursting point. It has been shown that the liquor folliculi of the pig has a distinct digestive action on ovarial tissue (Schochet) and this would play an important part in both the growth and rupture of the follicle, and, furthermore, it must not be forgotten that the ovarial stroma contains a considerable quantity of non-striped muscle tissue, a spasmodic contraction of which would produce a sudden increase of the intra-follicular tension. Normally the ovum when expelled from its follicle is received at once into the Fallopian tube, and so makes its way to the uterus, in whose cavity it undergoes its development. Occasionally, how- ever, this normal course may be interfered with, the ovum coming to rest in the tube and there undergoing its development and producing a tubal pregnancy; or, again, the ovum may not find its way into the Fallopian tube, but may fall from the follicle into the abdominal cavity, where, if it has been fertilized, it will under- go development, producing an abdominal pregnancy; and, finally, and still more rarely, the ovum may not be expelled when the Graafian follicle ruptures and yet may be fertilized and undergo its development within the follicle, bringing about what is termed an ovarian pregnancy. All these varieties of extra-uterine preg- nancy are, of course, exceedingly serious, since in none of them is the fetus viable. With the setting free of the ovum the usefulness of the Graafian follicle is at an end, and it begins at once to undergo retrogressive changes which result primarily in the formation of a structure known as the corpus luteum (Fig. 12). On the rupture of the follicle a considerable portion of the stratum granulosum remains in place, and the cells composing it undergo proliferation and develop in their substance a yellow pigment known as lutein, the color imparted to the follicle by this substance having suggested the name, corpus luteum, that is now applied to it. The blood- vessels of the theca interna become enlarged and hernia-like pro- trusions from them penetrate between the proliferating granulosa 24 OVULATION AND THE CORPUS LUTEUM cells, carrying with them a certain amount of connective tissue. Extravasations from the capillaries into the cavity of the follicle take place during the early stages of the vascularization of the granulosa, but in time the entire cavity of the follicle becomes filled with lutein cells, separated into groups by trabeculae of connective tissue containing blood-vessels, the corpus luteum thus reaching its maturity (Fig. 13). Fig. 13.— Section through the Corpus Luteum of a Rabbit, Seventy Hours post coitum. The cavity of the follicle is almost completely filled with lutein cells among which is a certain amount of connective tissue, g, Blood-vessels; ke, ovarial epithelium. — {Sohotta.) In later stages there is a gradual increase in the amount of con- nective tissue present and a corresponding diminution of the lutein cells, the corpus luteum gradually losing its yellow color and be- coming converted into a whitish, fibrous, scar-like body, the corpus albicans, which may eventually almost completely disappear. OVULATION AND THE CORPUS LUTEUM 2$ These various changes occur m every ruptured follicle, whether or not the ovum which was contained in it be fertilized. But the rapidity with which the various stages of retrogression ensue differs greatly according to whether pregnancy occurs or not, and it is customary to distinguish the corpora lutea which are associated with pregnancy as corpora lutea vera from those whose ova fail to be fertilized and which form corpora lutea spuria. In the latter the retrogression of the follicle is completed usually in about five or six weeks, while the corpora vera persist throughout the entire duration of the pregnancy and complete their retrogression after the birth of the child. In the account of the development of the corpus luteum given above the granulosa cells are described as being converted into the lutein cells. This is the opinion originally advanced by Bischoff, but another, which was held by von Baer, was for a time m.ore generally accepted. It maintained that the granulosa cells quickly underwent degeneration, the lutein cells and the entire mass of the corpus luteum being formed from the theca interna. The thor- ough study of the phenomena by Sobotta (1897) in a perfect series of mouse ovaries demonstrated that in that form the granu- losa cells persist and become converted into lutein cells, and later observations on other mammals, such as the rabbit (Sobotta), certain bats (Van der Stricht), the sheep (Marshall) , Spermophile (Volker, Drips), guinea-pig (Sobotta, L. Loeb) and various mar- supials (Sandes, O'Donaghue) confirmed the correctness of Sobotta*s conclusions. Adverse results were obtained from the study of the human corpus luteum by Clarke and from that of the pig by Jankowski, but the more recent observations of R . Mayer (191 1) make it altogether probable that in man, also, the granulosa are the chief source of the lutein cells and^Corner's (19 1 5) results lead him to believe that in the pig the granulosa cells persist and contribute to the formation of lutein. The participation of theca cells in the lutein formation is not, however, excluded, the hard and fast distinction frequently made between granulosa and thecal cells being probably unwarranted. The persistance of the corpus luteum throughout the period 26 THE RELATION OF OVULATION TO MENSTRUATION of pregnancy and its disappearance within a few weeks if preg- nancy failed to supervene, have suggested the probability of its being an organ of internal secretion directly concerned in the pro- duction of certain of the changes associated with pregnancy. It has been found that experimental removal of the corpus luteum in rabbits either before or shortly after the implantation of the ovum in the wall of the uterus produces a failure of pregnancy (Fraenkel) and similar results have been obtained in mice and bitches (Mar- shall and Jolly) and in Spermophiles (Drips). The cessation of ovulation which is characteristic of pregnancy has also been as- cribed to the action of the corpora lutea and there is experimental evidence in support of such a view (L. Loeb). But while the available evidence points to the existence of an internal secretion by the corpora lutea and to its having some influence in deter- mining the conditions associated with a successful pregnancy, the precise nature of its action is still obscure. The Relation of Ovulation to Menstruation. — It has long been believed that ovulation is coincident with certain periodic changes of the uterus which constitute what is termed menstrua- tion. This phenomenon makes its appearance at the time of puberty, the exact age at which it appears being determined by individual and racial peculiarities and by climate and other fac- tors, and after it has once appeared it normally recurs at definite intervals more or less closely corresponding with lunar months {i.e., at intervals of about twenty-eight days) until somewhere in the neighborhood of the fortieth or forty-fifth year, when it ceases. In each menstrual cycle four stages may be recognized, one of which, the intermenstrual, greatly exceeds the others in its duration, occupying about one-half the entire period. During this stage the mucous membrane of the uterus is practically at rest, but toward its close the membrane gradually begins to thicken and the second stage, the premenstrual stage, then supervenes. This lasts for six or seven days and is characterized by a marked proliferation and swelling of the uterine mucosa, the subjacent tissue becoming at the same time highly vascular and eventually congested. The walls of the blood-vessels situated beneath the mucosa then degen- THE RELATION OF OVULATION TO MENSTRUATION 27 erate and permit the escape of blood here and there beneath the mucous membrane, this leading to the third, or menstrual, stage in which the mucous membrane diminishes in thickness, those por- tions of it that overlie the effused blood undergoing fatty degenera- tion and desquamation, so that the stage is characterized by more or less extensive hemorrhage. The duration of this stage is from three to five days and then ensues the postmenstrual stage, lasting from four to six days, during which the mucous membrane is re- generated and again returns to the intermenstrual condition. It seems but natural to regard these changes as the expression of a periodic attempt to prepare the uterus for the reception of the fertilized ovum, this preparation being completed during the pre- menstrual stage, the succeeding menstrual and postmenstrual phenomenon being merely the return of the uterine mucosa to the resting intermenstrual stage, pregnancy not having occurred. If this be the real significance of the menstrual cycle, one would ex- pect to find ovulation occurring at a more or less definite portion of the cycle, at such a time that the ovum, if fertilized, would be able to make use of the premenstrual preparation for its reception. Since the occurence of a corpus luteum is the result of an ovula- tion and the age of the former can be determined within certain limits from its histological appearance, a comparison of the age of the corpus luteum with the condition of the uterine mucosa should indicate the period in the menstrual cycle when ovulation occurred . In other words since the development of the corpus luteum and the menstrual modifications of the uterine mucous membrane are both cylical phenomena, the question arises as to whether any correlation exists between the two and therefore between the proc- ess of ovulation and the condition of the uterine mucosa. It has been a very general belief that in the human species ovulation as a rule occurred at about the time of the menstrual flow, that is to say, just before, during, or just after the third stage of the men- strual cycle. Fraenkel, however, studied the condition of the corpus luteum in eighty-five cases in which the ovaries were re- moved in the course of operations and found that in ten, in which the operation had been performed immediately before or 28 THE MATURATION OF THE OVUM after menstruation, no corpus luteum was present and that in twenty in which a newly formed corpus luteum was found, the last menstruation had occured on the average nineteen (13-27) days previously. The criteria adopted by Fraenkel for determining the age of the corpora lutea do not seem to have been sufficiently precise and later observers confirming his conclusion that ovula- tion corresponded with a definite stage of the menstrual cycle, referred its occurrence to a somewhat earlier period of the cycle. Thus Willemin concluded that it occurred at about fifteen days after the beginning of menstruation; Grosser, not later than six- teen days; C. Ruge II, within fourteen days; and Schroeder between fourteen and sixteen days. These numbers represent, of course, an average from which there may be considerable deviation on either side, but they indicate that ovulation in the human species corresponds on the average with the middle of the intermenstrual period. The corpus luteum, accordingly, reaches its mature development during the premenstrual stage and may, therefore, be the determining cause of that stage (Schroeder) . In lower animals ovulation is, as a rule associated with a certain condition known as cesirus or *'heat," this being preceded by phenomena constituting what is termed procestrum and corresponding essentially to menstruation. In several forms, such as the dog, pig, horse and cow, ovulation occurs regularly in association with "heat," but in others, such as the cat, the ferret and the rabbit, it occurs at this time only if copulation also occurs. In the case of ;monkeys, although the females menstruate regularly throughout the year there is nevertheless but one annual cestral period when ovulation take place (Heape). The Maturation of the Ovimi.— Returning now to the ovum, it has been shown that at the time of its extrusion from the Graa- fian follicle it is not equivalent to a spermatozoon but to a primary spermatocyte, and it may be remembered that such a spermatocyte' becomes converted into a spermatozoon only after it has under- gone two divisions, during which there is a reduction of the number of the chromosomes to practically one-half the number characteristic for the species. THE MATURATION OF THE OVUM 29 Similar divisions and a similar reduction of the chromosomes occur in the case of the ovum, constituting what is termed its maturation. The phenomena have not as yet been observed in human ova, and, indeed, among mammals only with any approach to completeness in comparatively few forms (rat, mouse, guinea- pig, bat and cat) ; but they have been observed in so many other forms, both vertebrate and invertebrate, and present in all cases Fig. 14. — Ovum of a Mouse Showing the Maturation Spindle. The ovum is enclosed by the zona pellucida (z. p), to which the cells of the corona radiata are still attached. — {Sohotta.) SO much uniformity in their general features, that there can be little question as to their occurrence in the human ovum. In typical cases the ovum (the primary oocyte) undergoes a division in the prophases of which the chromatin aggregates to form half as many tetrads as there are chromosomes in the somatic cells (Fig. 15, oc^) and at the metaphase a dyad from each tetrad passes into each of the two cells that are formed. These two cells 30 THE MATURATION OF THE OVUM (secondary oocytes) are not, however, of the same size; one of them is almost as larg€ as the original primary oocyte and con- tinues to be called an ovum {oc'^), while the other is very small and is termed 3i polar globule (p). A second division of the ovum quickly succeeds the first (Fig. 15, oc"^), and each dyad gives a Fig. 15. — Diagram Illustrating the Reduction of the Chromosomes during THE Maturation of the Ovum. 0, Ovum; ocS oocyte of the first generation; oc^, oocyte of the second generation; p, polar globule. single chromosome to each of the two cells which result, so that each of these cells possess half the number of chromosomes charac- teristic for the species. The second division, like the first, is unequal, one of the cells being relatively very large and constituting the mature ovum, while the other is small and is the second polar THE FERTILIZATION OF THE OVUM 3 1 globule. Frequently the first polar globule divides during the formation of the second one, a reduction of its dyads to single chromosomes taking place, so that as the final result of the matura- tion four cells are formed (Fig. 15), the mature ovum {0), and three polar globules {p), each of which contains half the number of chromosomes characteristic for the species. The similarity of the maturation phenomena to those of sper- matogenesis may be perceived from the following diagram: nX"^ Spermalo- I 1 cyte I Oocyte II () O () C) ^Pfyuir OvuniO O 00 00 O O Spermatids Polar globules In both processes the number of cells produced is the same and in both there is a similar reduction of the chromosomes. But while each of the four spermatids is functional, the three polar globules are non-functional, and are to be regarded as abortive ova, formed during the process of reduction of the chromosomes only to under- go degeneration. In other words, three out of every four potential ova sacrifice themselves in order that the fourth may have the bulk, that is to say, the amount of nutritive material and cyto- plasm necessary for efficient development. The Fertilization of the Ovum. — It is perfectly clear that the reduction of the chromosomes in the germ cells cannot very long be repeated in successive generations unless a restoration of the original number takes place occasionally, and, as a matter of fact, such a restoration occurs at the very beginning of the develop- ment of each individual, being brought about by the union of a spermatozoon with an ovum. This union constitutes what is known as the fertilization of the ovum. 32 THE FERTILIZATION OF THE OVUM The fertilization of the human ovum has not been observed, but the phenomenon has been repeatedly studied in lower forms, and thorough studies of the process have been made on the mouse and the guinea-pig. The results obtained from these are taken as a basis for the following account. The maturation of the ovum is quite independent of fertiliza- tion, but in many forms the penetration of the spermatozoon into the ovum takes place before the maturation phenomena are com- pleted. This is the case with the mouse. A spermatozoon makes its way through the zona pellucida and becomes embedded in the cytoplasm of the .ovum and its tail is quickly absorbed by the cyto- plasm while its nucleus and probably the middle-piece persist as distinct structures. As soon as the maturation divisions are completed the nucleus of the ovum, now termed the female pro- nucleus (Fig. 1 6, ek)^ migrates toward the center of the ovum, and is now destitute of an archoplasm sphere and centrosome, these structures having disappeared after the completion of the matura- tion divisions. The spermatozoon nucleus, which, after it has penetrated the ovum, is termed male pronucleus (spk), may lie at first at almost any point in the peripheral part of the cytoplasm, and it now begins to approach the female pronucleus, preceded by the middle-piece, which becomes an archoplasm sphere with its contained centrosome and is surrounded by astral rays. The two pronuclei finally come into contact near the center of the ovum, forming what is termed the segmentation nucleus (Fig. i6), the archoplasm sphere and centrosome which have been introduced with the spermatozoon undergo division, the two archoplasm spheres so formed migrate to opposite poles of the segmentation nucleus, an amphiaster forms and the compound nucleus passes through the various prophases of mitosis. In describing the spermatogenesis it was shown (p. i6) that two classes of spermatozoa were formed in man, those of one class containing an X idiochromosome and the other a Y element, or if Guyer's results should prove to be more correct, one class con- taining ten ordinary chromosomes plus two idiochromosomes, while the other possesses only ordinary chromosomes. A similar THE FERTILIZATION OF THE OVUM 33 Fig. i6. — Six Stages in the Process of Fertilization of the Ovum of a Mouse. After the first stage figured it is impossible to determine which of the two nuclei represents the male or female pronucleus, ek. Female pronucleus; rki and rki, polar globules; spk, male pronucleus. — {Sobotta.) 34 tHE FERTILIZATION OF THE OVUM separation of the ova into two classes probably does^not occur, all possessing an X idiochromosome or two such elements as the case may be. When, therefore, the union of the male and female pronuclei takes place in fertilization, those ova that are fertilized by a spermatozoon with a Y idiochromosome will have twenty- c^ o B c^ Fig. 17. — Diagrams Illustrating Sex-determination in Man, A, on the Basis of the Spermatogenesis as Described by Wieman, B, according to Guyer's Account. four chromosomes, two of which are the X and Y idiochromosomes, while in those in which the fertilization is accomplished by a spermatozoon containing an X idiochromosome, there will also be twenty-four chromosomes, but two of these will be X idiochro- mosomes (Fig. 17, ^) . Or, according to Guyer's results, one group of ova will have twenty ordinary chromosomes plus four idiochro- THE FERTILIZATION OF THE OVUM 35 mosomes, while the other will have only two idiochromosomes (Fig. 17,^)- That either one or the other of these conditions occurs in the fertilization of the human ovum is merely a conjecture based on what has been shown to take place in a number of invertebrates and most clearly in insects. In these two classes of spermatozoa have been found to occur, as in man, the classes differing in some cases in the number and in others in the quality of their chromo- somes in their somatic cells, and when the spermatozoal differ- ence is one of quality in the chromosomes, the number being identical, it may be supposed that this difference also is transmitted to the adults. Further, there is strong evidence that those indi- viduals that develop from ova having the larger number of chromo- somes and that have themselves this larger number in their somatic cells are females, while those from ova with the smaller number of chromosomes and with the smaller number in their somatic cells are males; where the difference in the chromosomes is one of quality only the correlations just mentioned are not so readily perceived, though they may be presumed to exist. It would seem then that the sex of a given individual is determined by the pres- ence or absence or quality of the idiochromosomes in the fertilized ovum and is determined at the time of that fertilization. While great discrepancies occur in the various descriptions of human spermatogenesis, it seems probable that idiochromosomes occur in the human germ cells and it is justifiable to attribute to them the significance that has been so definitely shown to be attached to similar structures in insects. It seems to be a rule that but one spermatozoon penetrates the ovum. Many, of course, come into contact with it and endeavor to penetrate it, but as soon as one has been successful in its en- deavor no further penetration of others occurs. The reasons for this are in most cases obscure ; experiments on the ova of inverte- brates have shown that the subjection of the ova to abnormal conditions which impair their vitality favors the penetration of more than a single spermatozoon {polsy penny) , and, indeed, it appears that in some forms, such as the common newt (Diemy- 36 THE FERTILIZATION OF THE OVUM ctylus), polyspermy is the rule, only one of the spermatozoa, how- ever, which have penetrated uniting with the female pronucleus, the rest being absorbed by the cytoplasm of the ovum. Fertilization marks the beginning of development, and it is therefore important that something should be known as to where and when it occurs. It seems probable that in the human species the spermatozoa usually come into contact with the ovum and fertilize it in the upper part of the Fallopian tubes, and the occur- rence of extra-uterine pregnancy (see p. 23) seems to indicate that occasionally the ovum may be fertilized even before it has been received into the tube. It is evident, then, that when fertilization is accomplished the spermatozoon must have traveled a distance of about twenty-four centimeters, the length o the upper part of the vagina being taken to be about 5 cm., that of the uterus as 7 cm., and that of the tube as 12 cm. A considerable interval of time is required for the com- pletion of this journey, even though the movement of the sperma- tozoon be tolerably rapid. The observations of Henle and Hensen indicate that a spermatozoon may progress in a straight line at about the rate of from 1.2 to 2.7. mm. per minute, while Lott finds the rate to be as high as 3.6 mm. Assuming the rate of progress to be about 2.5 mm. per minute, the time required by the spe matozoon to travel from the upper part of the vagina to the upper part of a Fallopian tube will be about one and a half hours (Strass- mann). This, however, assumes that there are no obstacles in the way of the rapid progress of the spermatozoon, which is not the case, since, in the first place, the irregularities and folds of the lining membrane of the tube render the path of the spermatozoon a labyrinthine one, and, secondly, the action of the cilia of the epithelium of the tube and uterus being from the ostium of the tube toward the os uteri, it will greatly retard the progress; furthermore, it is presumable that the rapidity of movement of the spermatozoon diminishes after a certain interval of time. It seems probable, therefore, that fertilization does not occur for some hours after coition, even providing an ovum is in the tube awaiting the approach of the spermatozoon. SUPERFETATION 37 But this condition is not necessarily present, and consequently the question of the duration of the vitality of the sperm cell be- comes of importance. Ahlfeld has found that, when kept at a proper temperature, a spermatozoon will retain its vitality outside the body for eight days, and Diihrssen reports a case in which living spermatozoa were found in a Fallopian tube removed from a patient who had last been in coitu about three and a half weeks previously. As regards the duration of the vitality of the ovum less accurate data are available. Hyrtl found an apparently normal ovum in the uterine portion of the left tube of a female who died three days after the occurrence of her second menstrua- tion, and Issmer estimates the duration of the capacity for fertili- zation of an ovum to be about sixteen days. It is evident, then, that even when the date of the coitus that led to fertilization is known, the actual moment of the latter proc- ess and, therefore, the exact age of an embryo, can only be approximated (see p. 105). For the determination of the prob- able time of parturition the date of the last menstruation is in the majority of cases the only available datum and the statistics collected by Issmer show that in 1220 cases the duration of preg- nancy averaged 280 days, counting from the first day of the last menstruation. This corresponds to ten lunar and about nine calendar months, but an estimate on this basis is only an average from which considerable variation is possible. Superfetation. — ^The occasional occurrence of twin fetuses in different stages of development has suggested the possibility of the fertilization of a second ovum as the result of a coition at an appreci- able interval of time after the first ovum has started upon its devel- opment. There seems to be good reason for believing that many of the cases of supposed superfetation, as this phenomenon is termed, are instances of the simultaneous fertilization of two ova, one of which, for some cause concerned with the supply of nutrition, has later failed to develop as rapidly as the other. At the same time, however, even although the phenomenon may be of rare occurrence, it is by no means impossible, for occasionally a second Graafian follicle, either in the same or the other ovary, may be so near maturity, that its ovum is extruded soon after the first one, and if the development of the latter and the incidental changes in the uterine mucous membrane have not proceeded so far as to prevent the access of the sper- 3^ LITERATURE matozoon to the ovum, its fertilization and development may ensue. The changes, however, which prevent the passage of the spermatozoon are completed early in development and the difference between the normally developed embryo and that due to superfetation will be comparatively small, and will become less and less evident as devel- opment proceeds, provided that the supply of nutrition to both embryos is equal. LITERATURE E. Ballowitz: "Untersuchungen uber die Struktur der Spermatozoen," No. 4. Zeitschr. fur wissensch. Zool., lii, 1891. K. VON Bardeleben: "Beitrage zur Histologic des Hodens und zur Spermatogenese beim Menschen," Archiv fur Anat. und Physiol., Anat. Ahth., Supplement, 1897. Th. Boveri: " Befruchtung," Ergehnisse der Anat. und Entwicklungsgesch,. 1, 1892. J. G. Clark: "Ursprung, Wachsthum und Ende des Corpus luteum nach Beobach- tungen am Ovarium des Schweines und des Menschen," Archiv fiir Anat. und Physiol., Anat. Ahth., 1898. G. W. Corner: "The corpus luteum of pregnancy in Swine." Contrib. on Emhryol. ii, Carnegie Inst. Publ. 222, 191 5. D. Drips: "Studies on the ovary of the Spermophile (Spermophilus citnlus tridecim- lineatus) with special reference to the corpus luteum," Amer. Jour. Anat., xxv, 1919. L. Fraenkel: "Neue Experimente zur Function des Corpus luteum," Arch, fur Gynaek.fXd, 19 10. L. Fraenkel: "Das zeitliche Verhalten von Ovulation und Menstruation," Zenlralhl. fUrGynaek., 191 1. L. Fraenkel: "Ovulation, Konzeption und Schwangerschaftsdauer," Zeit. fur Gehurtsh. u. Gynaek., lxxiv, 19 13. L. Gerlach: "Ueber die Bildung der Richtungskorper bei Mus musculus," Wies- baden, 1906. O. Grosser: "Altersbestimmung junger menschlichen Embryonen — Ovulations und Menstruationstermin," Anat. Anz,XLVU, 1914. S. Gutherz: "Ueber ein bemerkenswertes Strukturelement (Heterochromosome) in der Spermiogenese des Menschen," Arch. f. mikr. Anat., lxxex, 1912. M. F. Guyer: "Accessory Chromosomes in Man," Biol. Bull., XJX, 1910. W. Heape: "The Sexual Season of Mammals and the Relation of the Preoestrum to Menstruation," Quart. Journ. Micros. Sci., N. S., xliv, 1901 (contains very full bibliography). O. Hertwig: "Vergleich der Ei- und Samenbildung bei Nematoden," Archiv fiir mikrosk. Anat.,XKXVi, 1890. F. HiTSCHMANN and L. Adler: "Der Bau der Uterusschleimhaut des geschlects- reifen Weibes, mit besonderer Berucksichtigung der Menstruation," Monatsschr. fiir Gehurtsh. und Gynaek., xxxii, 1908. J. Janowski: "Beitrag zur Entstehung des Corpus luteum der Saugetiere," Arch.f. mikr. Anat., Lxrv, 1904. W. B. Kirkham: "The Maturation of the Mouse Egg," Bioi, Bulletin^ xii, 1907. LITERATURE 39 W. B. KiRKHAM and H. S. Burr: "The breeding habits, maturation of eggs and ovulation of the albino rat," Amer. Jour. Anat., xv, 1913. H. Lams and J. Doorme: "Nouvelles recherches sur la maturation et la feconda- tion de I'oeuf de mammiferes," Arch, de Biol., xxiii, 1907. H. Lams: "Etude de I'oeuf de Cobaye aux premiers stades de I'embryogen^e,"- Arch, de Biol., xxviii, 1913. M. VON Lenhossek: "Untersuchungen uber Spermatogenese," Archiv filr mikrosk. Anat., LI, 1898. G. Leopold and A. Rovano: "Neuer Beitrag zur Lehre von der Menstruation und Ovulation," Arch, fiir Gynaek., lxxxiii, 1907. W. H. Longley: "The Maturation of the Egg and Ovulation in the Domestic Cat," Amer. Journ. Anat., xii, 191 1. F. H. A. Marshall: "The (Estrus Cycle and the Formation of the Corpus luteum in the Sheep," PMo^, Trans., Ser. B, cxcvi, 1904. F. H. A. Marshall: "The Development of the Corpus luteum: a Review," Qtiart. Journ. Micros. Sci., N. S., xlix, 1906. R. Mayer: "Ueber Corpus luteum Bildung beim Menschen," Arch, fiir Gynaek.^ xciii, 191 1. R. Mayer : "Ueber die Beziehung der Eizelle und des befruchteten Eies zutn FoUikel- apparat, sowie des Corpus luteum zum Menstruation," Arch, fiir Gynaek, c, 1913- F. Meves: "Ueber Struktur und Histogenese der Samenfaden des Meerschwein- chens," Archiv fiir mikrosk. Anat., liv, 1899. J. W. Miller: "Corpus luteum. Menstruation und Graviditat," Arch, fiir Gynaek, CI, 1914. T. H. Montgomery: "Differentiation of the human Cells of Sertoli," Biolog. Bull, XXI, 1911. T. H. Montgomery: "Human Spermatogenesis, Spermatocytes, and Spermiogene- sis: A study in Inheritance," Jour. Acad. Nat. Sci., Phila., Ser. 2, xv, 1912. W. Nagel: "Das menschliche Ei," Archiv fiir mikrosk. Anat., xxxi, 1888. G. Niessing: "Die Betheiligung der Centralkorper und Sphare am Aufbau des Samenfadens bei Saugethieren," Archiv fiir mikrosk.. Anat., XLVin, 1896. G. Retzius: "Die Spermien des Menschen," Biolog. Untersuch.,xiv, 1909. W. Rubaschkin: "Ueber die Reifungs- und Befruchtungs-processe des Meer- schweincheneies," Anat. Hefte, xxrx, 1905. C. Ruge II: "Ueber Ovulation, Corpus luteum und Menstruation," Arch, fiir Gynaek., c, 19 13. S. S. Schochet: "A suggestion as to the process of ovulation and ovarian cyst formation," Anat. Record, x, 1916. J. Sobotta: "Die Befruchtung und Furchung des Eies der Maus," Archiv fUr mik- rosk. Anat., XLV, 1895. J. Sobotta: "Ueber die Bildung des Corpus luteum bei der Maus," Archiv fiir mikrosk. Anat., xlvii, 1897. J. Sobotta: "Ueber die Bildung des Corpus luteum beim Meerschweinchen," Anat., Hefte, xxxii, 1906. J. Sobotta and G. Burckhard: "Reifung und Befruchtung der Eier des weissen Ratte," Anat. Hefte, xlu, 1910. 40 LITERATURE P. Strassmann : " Beitrage zur Lehre von der Ovulation, Menstruation und Con- ception," Archiv fiir Gynaekol, Lii, 1896. O. Van der Stricht: "Sur le processus de I'excretion des glandes endocrines, le corps jaune et la glande interstitielle de I'ovaire;" Arch, de Biol, xxvii, 191 2. F. Villemin: "Le corps jaune considere comme glande a. secretion interne," Paris, 1908. H. VON Winiwarter: "Etudes sur la spermatogenese humaine," Arch, de Biol., XXVII, 1912. W. Waldeyer: "Eierstock und Ei," Leipzig, 1870. H. L. Wieman: "The chromosomes of human spermatocytes," Anier. Journ., Anat., XXI, 191 7. CHAPTER II THE SEGMENTATION OF THE OVUM AND THE FORMATION OF THE GERM LAYERS Segmentation. — The union of the male and female pronuclei has already been described as being accompanied by the formation of a mitotic spindle which produces a division of the ovum into two cells. This first division is succeeded at more or less regular intervals by others, until a mass of cells is produced in which a differentiation eventually appears. These divisions of the ovum constitute what is termed its segmentation. The mammalian ovum has behind it a long line of evolution, and even at early stages in its development it exhibits peculiarities which can be reasonably explained only as an inheritance of past conditions. One of the most potent factors in modifying the char- acter of the segmentation of the ovum is the amount of food yolk which it contains, and it seems to be certain that the immediate ancestors of the mammalia were forms whose ova contained a con- siderable amount of yolk, many of the peculiarities resulting from its presence being s.till clearly indicated in the early development of the almost yolkless human ovum. To give some idea of the peculiarities which result from the presence of considerable amounts of yolk it will be well to compare the processes of segmen- tation and differentiation seen in ova with different amounts of it. A little below the scale of the vertebrates proper is a form, Amphioxus, which possesses an almost yolkless ovum, presenting a simple process of development. The fertilized ovum of Amphi- oxus in its first division separates into two similar and equal cells, and these are made four (Fig. i8, A) by a second plane of division which cuts the previous one at right angles. A third plane at right angles to both the preceding ones brings about an eight- 41 42 THE SEGMENTATION OF THE OVUM celled stage (Fig. i8, B), and further divisions result in the forma- tion of a large number of cells which arrange themselves in the form of a hollow sphere which is known as a hlastula (Fig. i8, £). The minute amount of yolk which is present in the ovum of Amphioxus collects at an early stage of the segmentation at one pole of the ovum, the cells containing it being somewhat larger than those of the other pole (Fig. i8, B), and in the bias tula the cells of one pole are larger and more richly laden with yolk than those of the other pole (Fig. i8, F). If, now, the segmenting ovum of an Amphibian be examined, it will be found that a very Fig. 1 8. — Stages in the Segmentation of Amphioxus. A, Four-celled stage; B, eight-celled stage; C, sixteen-celled stage; D, early blastuh E, blastula; F, section of blastula. — (Hatschek.) much greater amount of yolk is present and, as in Amphioxus, it is located especially at one pole of the ovum. The first three planes of segmentation have the same relative positions as in Amphioxus (Fig. i8), but one of the tiers of cells of the eight-celled stage is very much smaller than the other (Fig. 19, B). In the subsequent stages of segmentation the small cells of the upper pole divide more rapidly than the larger ones of the lower pole, the activity of the latter seeming to be retarded by the accumula- tion of the yolk, and the resulting blastula (Fig. 19, D) shows a very decided difference in the size of the cells of the two poles. THE SEGMENTATION OF THE OVUM 43 In the ova of reptiles and birds the amount of yolk stored up in the ovum is very much greater than in the amphibia, and it is aggregated at one pole of the ovum, of which it forms the principal mass, the yolkless protoplasm appearing as a small disk upon the surface of a relatively huge mass of yolk. The inertia of this mass of nutritive material is so great that the segmentation is confined to the small yolkless disk of protoplasm and affects ^^^^ C D Fig. 19. — Stages in the Segmentation of Amhlysioma. — {Eycleshymer.) consequently only a portion of the entire ovum. To distinguish this form of segmentation from that which affects the entire ovum it is termed merohlastic segmentation, the other form being known as holoblastic. In the ovum of a turtle or a bird the first plane of segmentation crosses the protoplasmic disk, dividing it into two practically equal halves, and the second plane forms at approximately right angles to the first one, dividing the disk into four quadrants (Fig. 44 THE SEGMENTATION OF THE OVUM 20, A). The third division, like the two which precede it, is radial in position, while the fourth is circular and cuts off the inner ends of the six cells previously formed (Fig. 20, C). The disk now con- sists of six central smaller cells surrounded by six larger peripheral ones. Beyond this period no regularity can be discerned in the appearance of the segmentation planes; but radial and circular divisions continuing to form, the disk becomes divided into a I) Fig. 20. — Four Stages in the Segmentation of the Blastoderm of the Chick. — iCoste.) large number of cells, those at the center being much smaller than those at the periphery. In the meantime, however, the smaller central cells have begun to divide in planes parallel to the surface of the disk, which, from being a simple plate of cells, thus becomes a discoidal cell-mass. During the segmentation of the disk it has increased materially in size, extending further and further over the surface of the yolk, into the substance of which some of the lower cells of the discoidal THE SEGMENTATION OF THE OVUM 45 cell-mass have penetrated. A comparison of the diagram (Fig. 2i) of the ovum of a reptile at about this stage of development with the figure of the amphibian bias tula (Fig. 19, D) will indicate the similarity between the two, the large yolk-mass (F) of the" reptile with the scattered cells which it contains corresponding to the lower pole cells of the amphibian blastula, the central cavity of which is practically suppressed in the reptile. Beyond this stage, however, the similarity becomes more obscured. The peri- pheral cells of the disk continue to extend over the surface of the yolk and finally completely enclose it, forming an enveloping Fig. 21. — Diagram Illustrating a Section of the Ovum of a Reptile at a Stage Corresponding to the Blastula of an Amphibian. hi. Blastoderm; Y, yolk-mass. layer which is completed at the upper pole of the egg by the dis- coidal cell-mass, or, as it is usually termed, the blastoderm. Turning now to the mammalia,* it will be found that the ovum in the great majority is almost or quite as destitute of food yolk as is the ovum of Amphioxus, with the result that the segmenta- tion is of the total or holoblastic type. It does not, however, proceed with that regularity which marks the segmentation of Amphioxus or an amphibian, but while at first it divides into two slightly unequal cells (Fig. 22), thereafter the divisions be- * The segmentation of the human ovum has not yet been observed; what follows is based on what occurs in the ovum of the rabbit, mole, and especially of a bat (Van Beneden) . 46 THE SEGMENTATION OF THE OVUM come irregular, three-celled, four-celled, five-celled, and six-celled stages having been observed in various instances. Nor is the result of the final segmentation a hollow vesicle or blastula, but a solid mass of cells, termed a morula, is formed. This structure is not, however, comparable to the blastula of the lower forms, but Fig. 22. — Pour Stages in the Segmentation of the Ovum of a Mouse. X, Polar globule. — (Sobotta.) corresponds to a stage of reptilian development a little later than that shown in Fig. 21, since, as will be shown directly, the cells corresponding to the blastoderm and the enveloping layer are already present. There is, then, no blastula stage in the mam- malian development Differentiation now begins by the peripheral cells of the morula becoming less spherical in shape and later forming a layer of flat- tened cells, the enveloping layer, surrounding the more spherical THE SEGMENTATION OF THE OVUM 47 central cells (Fig. 23, A). In the latter vacuoles now make their appearance, especially in those cells which are nearest what may C D Fig. 23. — Later Stages in the Segmentation of the Ovum of a Bat. A. C, and D are sections, B a surface view. — (Van Beneden.) be regarded as the lower pole of the ovum (Fig. 22, C) and these vacuoles, gradually increasing in size, eventually become confluent, 48 TWIN DEVELOPMENT AND DOUBLE MONSTERS the condition represented in Fig. 23, D, being produced. At this stage the ovum consists of an enveloping layer, enclosing a cavity which is equivalent to the yolk-mass of the reptilian ovum, the vacuolization of the inner cells of the morula representing a belated formation of yolk. On the inner surface of the enveloping layer, at what may be termed the upper pole of the ovum, is a mass of cells projecting into the yolk-cavity and forming what is known as the inner cell-mass, a structure comparable to the blastoderm of the reptile. In one respect, however, a difference obtains, the inner cell-mass being completely enclosed within the enveloping cells, which is not the case with the blastoderm of the reptile. That portion of the enveloping layer which covers the cell-mass has been termed Rauber^s covering layer, and probably owes its existence to the precocity of the formation of the enveloping layer. It is clear, then, that an explanation of the early stages of development of the mammalian ovum is to be obtained by a com- parison, not with a yolkless ovum such as that of Amphioxus, but with an ovum richly laden with yolk, such as the meroblastic ovum of a reptile or bird. In these forms the nutrition necessary for the growth of the embryo and for the complicated processes of development is provided for by the storing up of a quantity of yolk in the ovum, the embryo being thus independent of external sources for food. The same is true also of the lowest mammalia, the Monotremes, which are egg-laying forms producing ova resembling greatly those of a reptile. When, however, in the higher mammals the nutrition of the embryo became provided for by the attachment of the embryo to the walls of the uterus of the parent so that it could be nourished directly by the parent, the storing up of yolk in the ovum was unnecessary and it became a holoblastic ovum, although many peculiarities dependent on the original meroblastic condition persisted in its development. Twin Development. — ^As a rule, in the human species but one embryo develops at a time, but the occurrence of twins is by no means infrequent, and triplets and even quadruplets occasinoally are developed. The occurrence of twins may be due to two causes, either to the simultaneous ripening and fertilization of two ova, either from one or from both ovaries, or to the separation of a single fertilized TWIN DEVELOPMENT AND DOUBLE MONSTERS 49 ovum into two independent parts during the early stages of develop- ment. That twins may be produced by this latter process has been abundantly shown by experimentation upon developing ova of lower forms, each of the two cells of an Amphioxus ovum in that stage of development, if mechanically separated, completing its development' and producing an embryo of about half the normal size. Furthermore, it has been shown (Patterson) that in the armadillo a division of the embryonic anlage into four parts at an early stage of the develop- ment is a normal process, the four young produced at a birth being quadruplets produced from a single ovum. It is noteworthy that in the case of the armadillo the four indi- viduals of each birth are of the same sex, and it is probable that human twins of the same sex and closely similar in appearance, what are termed "like" twins, are the result of a division of a single embryonic anlage, while "unlike" twins are produced by the simultaneous fer- tilization of two separate ova. Double Monsters and the Duplication of Parts. — The occasional occurrence of double monsters is explained by an imperfect separation into two parts of an originally single embryo, the extent of the separa- tion, and probably also the stage of development at which it occurs, determining the amount of fusion of the two individuals constituting the monster. All gradations of separation occur, from almost complete separation, as seen in such cases as the Siamese twins, to forms in which the two individuals are unite throughout the entire length of their bodies. The separation may also afiFect only a portion of the embryo, producing, for instance, double-faced or double-headed mon- sters or various forms of so-called parasitic monsters; and finally, it may affect only a group of cells destined to from a special organ, producing an excess of parts, such as supernumerary digits or accessory spleens. It has been observed in the case of double monsters that one of the two fused individuals always has the position of its various organs reversed, it being, as it were, the looking-glass image of its fellow. Cases of a similar situs inversus visceruntj as it is called, have not in- frequently been observed in single individuals, and a plausible ex- planation of such cases regards them as one of a pair of twins formed by the incomplete division of a single embryo, the other individual having ceased to develop and either having undergone degeneration or having been included within the body of the apparently single indivi- dual. Another explanation of situs inversus has been advanced (Con- klin) on the basis of what has been observed in certain invertebrates. In some species of snails situs inversus is a noimal condition and it has been found that the inversion may be traced back in the development even to the earliest segmentation stages. The conclusion is thereby indicated that its primary cause may reside in an inversion of the polarity of the ovum, evidence being forthcoming in favor of the view that even in the ovum of these and other forms there is probably a 50 FORMATION OF THE GERM LAYERS distinct polar differentiation. How far this view may be applicable to the mammalian ovum is uncertain, but if it be applicable it explains the phenomenon of inversion without complicating it with the question of twin-formation. The Formation of the Germ Layers. — During the stages which have been described as belonging to the segmentation period of development there has been but little differentiation of the cells. In Amphioxus and the amphibians the cells at one pole of the bjastula are larger and more yolk-laden than those at the other pole, and in the mammals an inner cell-mass can be distinguished from the enveloping cells, this latter differentiation having been A B Pig. 24. — Two Stages in the Gastrulation of Amphioxus. — {Morgan and Hazen.) anticipated in the reptiles and being a differentiation of a portion of the ovum, from which alone the embryo will develop, from a portion which will give rise to accessory structures. In later stages a differentiation of the inner cell-mass occurs, resulting first of all in the formation of a two-layered or diplohlastic and later of a three-layered or triplohlastic stage. Just as the segmentation has been shown to be profoundly modified by the amount of yolk present in the ovum and by its secondary reduction, so, too, the formation of the three primitive layers is much modified by the same cause, and to get a clear understanding of the formation of the triplohlastic condition of the mammal it will be necessary to describe briefly its develop- ment in lower forms. FORMATION OF THE GERM LAYERS 51 In Amphioxus the diploblastic condition results from the flat- tening of the large-celled pole of the blastula (Fig. 24, A), and finally from the invagination of this portion of the vesicle within the other portion (Fig. 24, B). The original single-walled blastula in this way becomes converted into a double-walled sac termed a gastrula, the outer layer of which is known as the ectoderm or epihlast and the inner layer as the endoderm or hypoblast. The cavity bounded by the endoderm is the primitive gut or archen- teron, and the opening by which this communicates with the ex- terior is the blastopore. This last structure is at first a very wide opening, but as development pro- ceeds it becomes smaller, and finally is a relatively small open- ing situated at the posterior ex- tremity of what will be the dorsal surface of the embryo. As the oval embryo continues to elongate in its later develop- ment the third layer or mesoderm makes its appearance. It arises as a lateral fold (mp) of the dorsal Fig. 25. — Transverse Section of A mphioxus Embryo with Five Mesodermic Pouches. Ch, Notochord; d, digestive cavity; surface of the endoderm (en) on ^c, ectoderm; en, endoderm; m, medul- 1 •J r ,1 -jji T • lary plate; mp, mesodermic pouch. — each side of the middle line as m- (Hatschek.) dicated in the transverse section shown in Fig. 25. This fold eventually becomes completely con- stricted off from the endoderm and forms a hollow plate oc- cupying the space between the ectoderm and endoderm, the cavity which it contains being the body-cavity or ccelom. In the amphibia, where the amount of yolk is very much greater than in Amphioxus, the gastrulation becomes considerably modi- fied. On the line where the large- and small-celled portions of the blastula become continuous a crescentic groove appears and, deepening, forms an invagination (Fig. 26, gc), the roof of which is composed of relatively small yolk-containing cells while its floor is formed by the large cells of the lower pole of the blastula. The 52 FORMATION OF THE GERM LAYERS cavity of the blastula is not sufficiently large to allow of the typical invagination of all these large cells, so that they become enclosed by the rapid growth of the ectoderm cells of the upper pole of the ovum over them. Before this growth takes place the blastopore corresponds to the entire area occupied by the large yolk cells, but later, as the growth of the smaller cells gradually encloses the larger ones, it becomes smaller and is finally represented by a Pig. 26. — Section through a Gastrula of Ambly stoma, dl, Dorsal lip of blastopore; gc, digestive cavity; gr, area of mesoderm formation; mes, mesoderm. — (Eycleshymer.) small opening situated at what w'll be the hind end of the embryo. Soon after the archenteron has been formed a solid plate of cells, eventually splitting into two layers, arises from its roof on each side of the median line and grows out into the space between the ectoderm and endoderm (Fig. 27, mk^ and mk^), evidently corresponding to the hollow plates formed in the same situations in Amphioxus. This is not, however, the only source of the mesoderm in the amphibia, for while the blastopore is still quite large there may be found surrounding it, between the endoderm and ectoderm, a ring of mesodermal tissue (Fig. 26, mes). As the FORMATION OF THE GERM LAYERS 53 blastopore diminishes in size and its lips come together and unite, the ring of mesoderm forms first an oval and then a band lying beneath the line of closure of the blastopore and united with both the superjacent ectoderm and the subjacent endoderm. This line of fusion of the three germ layers is known as the primitive streak. It is convenient to distinguish the mesoderm of the primitive streak from that formed from the dorsal wall of the archenteron by speaking of the former as the prostomial and the latter as the gastral mesoderm, though it must be understood that Fig. 27. — Section through an Embryo Amphibian (Triton) of 2% Days, show- ing THE Formation of the Gastral Mesoderm. ak, Ectoderm; ch, chorda endoderm; dk, digestive cavity; ik, endoderm; mk^ and mk"^, somatic and splanchnic layers of the mesoderm. D, dorsal and F, ventral. — {Her twig.) the two are continuous immediately in front of the definitive blastopore. In the reptilia still greater modifications are found in the method of formation of the germ layers. Before the enveloping cells have completely surrounded the yolk-mass, a crescen tic groove, resembling that occurring in amphibia, appears near the posterior edge of the blastoderm the cells of which, in front of the groove, arrange themselves in a superficial layer one cell thick, which may be regarded as the ectoderm (Fig. 28, ec), and a subjacent mass of somewhat scattered cells. Later the lowermost cells of this sub- jacent mass arrange themselves in a continuous layer, constituting 54 rORMATION OF THE GERM LAYERS what is termed the^ primary endoderm (en^), while the remaining cells, aggregated especially in the region of the crescentic groove, form the prostomial mesoderm {prm). In the region enclosed by the groove a distinct delimitation of the various layers does not occur, and this region forms the primitive streak. The groove now begins to deepen, forming an invagination of secondary en- doderm, the extent of this invagination being, however, very different in different species. In the gecko (Will) it pushes for- •ei^ikmt® ^^ prm ^"?3E1^ ec en Fig. 28. — Longitudinal Sections through Blastoderms of the Gecko, showing Gastrulation. ec, Ectoderm; en, secondary endoderm; en\ primary endoderm; prm, prostomial mesoderm. — {Will.) ^ ward between the ectoderm and primary endoderm almost to the anterior edge of the blastoderm (Fig. 28, B), but later the cells forming its floor, together with those of the primary endoderm immediately below, undergo a degeneration, the roof cells at the tip and lateral margins of the invagination becoming continuous with the persisting portions of the primary endoderm (Figs. 28, C and 29, B). This layer, following the enveloping cells in their growth over the yolk-mass, gradually surrounds that structure so FORMATION OF THE GERM LAYERS 55 that it comes to lie within the archenteron. In some turtles, on the other hand, the disappearance of the floor of the invagination takes place at a very early stage of the infolding, the roof cells only persisting to grow forward to form the dorsal wall of the arch- enteron. This interesting abbreviation of the process occurring in the gecko indicates the mode of development which is found in the mammalia. The existence of a prostomial mesoderm in connection with the primitive streak has already been noted, and when the invagina- tion takes place it is carried forward as a narrow band of cells on ec en Fig. 29. — Diagrams Illustrating the Formation of the Gastral Mesoderm IN the Gecko. e. Chorda endoderm; ec, ectoderm; en, secondary endoderm; en,^ primary endoderm gm, gastral mesoderm. — i^ill.) each side of the sac of secondary endoderm. After the absorption of the ventral wall of the invagination a folding or turning in of the margins of the secondary endoderm occurs (Fig. 29), whereby its lumen becomes reduced in size and it passes off on each side into a double plate of cells which constitute the gastral mesoderm. Later these plates separate from the archenteron as in the lower forms. All the prostomial mesoderm does not, however, arise from the primitive streak region, but a considerable amount also 56 FORMATION OF THE GERM LAYERS has its origin from the ectoderm covering the yoke outside the lim- its of the blastoderm proper, a mode of origin which serves to ex- plain the phenomena later to be described for the mammalia. Fig. 30. — Sections of Ova of a Bat Showing (A) the Formation of the Endo- DERM AND {B AND C) OF THE AMNIOTIC Cavity. — {Van Betiedeti.) In comparison with the amphibians and Amphioxus, the rep- tilia present a subordination of the process of invagination in the formation of the endoderm, a primary endoderm making its appear- FORMATION OF THE GERM LAYERS 57 ance independently of an invagination, and, in association with this subordination, there is an early appearance of the primitive streak, which, from analogy with what occurs in the amphibia^ may be assumed to represent a portion of the blastopore which is closed from the very beginning. Turning now to the mammalia, it will be found that these peculiarities become still more emphasized. The inner cell-mass of these forms corresponds to the blastoderm of the reptilian ovum, and the first differentiation which appears in it concerns the cells situated next the cavity of the vesicle, these cells differentiat- ing to form a distinct layer which gradually extends so as to form a complete lining to the inner surface of the enveloping cells (Fig. 30, A ) . The layer so formed is endodermal and corresponds to the pri- mary endoderm of the reptiles. Before the extension of the endoderm is completed, however, cavities begin to appear in the cells constituting the remainder of the inner mass, especially in those immediately beneath Rauber's cells (Fig. 30, B), and these cavities in time coalesce to form a single large cavity bounded above by cells of the enveloping layer and below by a thick plate of cells, the embryonic disk (Fig. 29, C). The cavity so formed is the amniotic cavity, whose further history will be considered in a subsequent chapter. It may be stated that this cavity varies greatly in its development in different mammals, being entirely absent in the rabbit at this stage of development and reaching an excessive development in such forms as the rat, mouse, and guinea-pig. The condition here described is that which occurs in the bat and the mole, and it seems probable, from what occurs in the youngest human embryos hitherto observed, that the processes in man are closely similar. While these changes have been taking place a splitting of the enveloping layer has occurred (Fig. 30, C), it becoming divided into an outer layer whose cells unite to form a syncytium, and an inner one in which the cell boundaries remain distinct. The two layers together form what is termed the trophoblast, from the part it subsequently plays in the nutrition of the embryo, the outer layer being the plasmodi-trophoblast and the inner the cyto- 58 FORMATION OF THE GERM LAYERS Irophohlast. In the bat of whose ovum Fig. 30 C, represents a section, that portion of the cyto-trophoblast which forms the roof of the amniotic cavity disappears, only the plasmodi-tropho- blast persisting in this region, but in another form this is not the case, the roof of the cavity bevng composed of both layers of the trophoblast. A rabbit's ovum in which there is yet no amniotic cavity and no splitting of the enveloping layer shows, when viewed from above, Pig. 31. — A, Side View of Ovum of Rabbit Seven Days Old (Kolliker); B» Embryonic Disk of a Mole (Heape); C, Embryonic Disk of a Dog's Ovum of ABOUT Fifteen Days {Bonnet). ed. Embryonic disk; hn, Hensen's node; mg, medullary groove; ps, primitive streak; va, vascular area. a relatively small dark area on the surface, which is the embryonic disk. But if it be looked at from the side (Fig. 31, A), it will be seen that the upper half of the ovum, that half in which the em- bryonic disk occurs, is somewhat darker than the lower half, the line of separation of the two shades corresponding with the edge of the primary endoderm which has entended so far in its growth around the inner surface of the enveloping layer. A little later a dark area appears at one end of the embryonic disk, produced by FORMATION OF THE GERM LAYERS 59 a proliferation of cells in this region and having a somewhat cres- centic form. As the embryonic disk increases in size a longitudinal band makes its appearance, extending forward in the median line nearly to the center of the disk, and represents the primitive streak (Fig. 31, 5), a slight groove along its median line forming what is termed the primitive groove. In slightly later stages an especially dark spot may be seen at the front end of the primitive streak and is term^di Hensen's node (Fig. 31, C, hn), while still later a dark streak may be observed extending forward from this in the median line arid is termed the head process of the primitive streak. Fig. 32. — Posterior Portion of a Longitudinal Section through the Em- bryonic Disk of a Mole. hi. Blastopore, ec, ectoderm; en, endoderm; prm, prostotnial mesoderm. — {After Heape.) To understand the meaning of these various dark areas re- course must be had to the study of sections. A longitudinal section through the embryonic d^'sk of a mole ovum at the time when the crescentic area makes its appearance is shown in Fig. 32. Here there is to be seen near the hinder edge of the disk what is potentially an opening (bl) , in front of which the ectoderm (ec) and primary endoderm (en) can be clearly distinguished, while behind it no such distinction of the two layers is visible. This stage may be regarded as comparable to a stage immediately preceding the invagination stage of the reptilian ovum, and the region behind the blastopore will correspond to the reptilian primitive streak. The later forward extension of the primitive streak is due to the mode of growth of the embryonic disk. Between the stages repre- sented in Figs. 32 and 31, B, the disk has enlarged considerably and the primitive streak has shared in its elongation. Since the blastopore of the earlier stage is situated immediately in front of 6o FORMATION OF THE GERM LAYERS the anterior extremity of the primitive streak, the point corres- ponding to it in the older disk is occupied by Hensen's node, this structure, therefore, representing a proliferation of cells from the region formerly occupied by the blastopore. As regards the head process, it is at first a solid cord of cells _,i»r Pig. 33- — Transverse Section of the Embryonic Area of a Dog's Ovum at ABOUT THE StAGE OF DEVELOPMENT SHOWN IN FiG, 30,C. The section passes through the head process (Chp); M, mesoderm. — (Bonnet.) which grows forward in the median line from Hensen's node, lying between the ectoderm and the primary endoderm. Later a lumen appears in the center of the cord, forming what has been termed the chorda canal, and, in some forms, including man, the canal Fig. 34. — Diagram of a Longitudinal Section through the Embryonic Disk of A Mole. am, Amnion; ce, chorda endoderm; ec, ectoderm; nc, neurenteric canal; ps, primitive streak. — (Heape.) opens to the surface at the center of Hensen's node. The cord then fuses with the subjacent primary endoderm and then opens out along the line of fusion, becoming thus transformed into a flat plate of cells continuous at either side with the primary endo- derm (Fig. ^^, Chp). The portion of the chorda canal which FORMATION OF THE GERM LAYERS 6 1 traverses Hensen's node now opens below into what will be the primitive digestive tract and is termed the neurenteric canal (Fig. 34, nc) ; it eventually closes completely, being merely a transitory structure. The similarity of the head process to the invagination which in the reptilia forms the secondary endoderm seems clear, the only essential difference being that in the mammalia the head process arises as a solid cord which subsequently becomes hollow, instead of as an actual invagination. The difference accounts for the occurrence of Hensen's node and also for the mode of forma- tion of the neurenteric canal, and cannot be considered as of great moment since the development of what are eventually tubular Fig, 35. — Transverse Section through the Embryonic Disk of a Rabbit. ch. Chorda endoderm; ee, ectoderm; en, endoderm; gm, gastral mesoderm. — {After van Beneden.) structures {e.g., glands) as solid cords of cells which subsequently hollow out is of common occurrence in the mammalia. It should be stated that in some mammals apparently the most anterior portion of the roof of the archenteron is formed directly from the cells of the primary endoderm, which in this region are not re- placed by the head process, but aggregate to form a compact plate of cells with which the anterior extremity of the head process unites. Such a condition would represent a further modification of the original condition. As regards the formation of the embryonic mesoderm it is not always possible to recognize both the prostomial and gastral mesoderm in the mammalian ovum. A mass of pros- tomial mesoderm is formed from the primitive streak and as the head process grows forward a band of this mesoderm extends for- ward on either side of it, but whether contributions are added to 62 FORMATION OF THE GERM LAYERS these bands from the head process is uncertain. Later on the medial margins of the bands come into intimate relation with the head process or chorda endoderm, just where this unites with the primitive endoderm, and an appearance may be presented closely similar to that shown in reptilia (compare Fig. 29, D and Fig. 35). If, in the mammalia the head process tissue takes no part in the formation of these lateral plates of mesoderm it may be supposed that a concentration of the development has taken place, the ABC D Pig. 36. — Diagrams Illustrating the Relations of the Chick Embryo to the Primitive Streak at Different Stages of Development, — {Peebles.) head process being composed purely of chorda endoderm, while the mesoderm associated with this in the reptilia now takes its origin directly from the primitive streak. The lateral plates of mesoderm are at first solid (Fig. 35, gm), but their cells early ar- range themselves in two layers, between which a space, termed the body-cavity or coelom, later appears. In addition to this embryonic mesoderm a certain amount, sometimes quite large, of the same layer is found lining the inner surface of the cytotrophoblast, lying between this and the primary SIGNIFICANCE OF THE GERM LAYERS 63 endoderm. The exact source of this extra-embryonic mesoderm is uncertain, though it seems probable that it is formed in situ, and is perhaps represented in the reptilian ovum by the cells which underlie the ectoderm in the regions peripheral to the blastoderm proper (seepage 55). It has been experimentally determined (Assheton, Peebles) that in the chick, whose embryonic disk presents many features similar to those of the mammalian ovum, the central point of the unincubated disk corresponds to the anterior end of the primitive streak and to the point situated immediately behind the heart of the later embryo and immediately in front of the first mesodermic somite (see p. 79), as shown in Fig. 36. If these results be regarded as applicable to the human embryo, then it may be supposed that in this the head region is developed from the portion of the embryonic disk situated in front of Hensen's node, while the entire trunk is a product of the region occupied by the node. The Significance of the Germ Layers. — The formation of the three germ layers is a process of fundamental importance, since it is a differentiation of the cell units of the ovum into tissues which have definite tasks to fulfil. As has been seen, the first stage in the development of the layers is the formation of the ectoderm and endoderm, or, if the physiological nature of the layers be considered, it is the differentiation of a layer, the endoderm, which has princi- pally nutritive functions. In certain of the lower invertebrates, the class Coelentera, the differentiation does not proceed beyond this diploblastic stage, but in all higher forms the intermediate layer is also developed, and with its appearance a further division of the functions of the organism supervenes, the ectoderm, situated upon the outside of the body, assuming the relational functions, the endoderm becoming still more exclusively nutritive, while the remaining functions, supportive, excretory, locomotor, reproduc- tive, etc. are assumed by the mesoderm. The manifold adaptations of development obscure in certain cases the fundamental relations of the three layers, certain por- tions of the mesoderm, for instance, failing to differentiate simul- taneously with the rest of the layer and appearing therefore to be a portion of either the ectoderm or endoderm. But, as a rule, the 64 SIGNIFICANCE OF THE GERM LAYERS layers are structural units of a higher order than the cells, and since each assumes definite physiological functions, definite structures have their origin from each. Thus from the ectoderm there develop: 1. The epidermis and its appendages, hairs, nails, epidermal glands, and the enamel of the teeth. 2. The epithelium lining the mouth and the nasal cavities, as well as that lining the lower part of the rectum. 3. The nervous system and the nervous elements of the sense- organs, together with the lens of the eye. From the endoderm develop: 1. The epithelium lining the digestive tract in general, together with that of the various glands associated with it, such as the liver and pancreas. 2. The lining epithelium of the larynx, trachea, and lungs. 3. The epithelium of the bladder and urethra (in part). From the mesoderm there are formed : 1. The various connective tissues, including bone and the teeth (except the enamel) . 2. The muscles, both striated and non-striated. 3. The circulatory system, including the blood itself and the lymphatic system. 4. The lining membrane of the serous cavities of the body. 5. The kidneys and ureters. 6. The internal organs of reproduction. From this list it will be seen that the products of the mesoderm are more varied than those of either of the other layers. Among its products are organs in which in either the embryonic or adult condition the cells are arranged in a definite layer, while in other structures its cells are scattered in a matrix of non-cellular ma- terial, as, for example, in the connective tissue, bone, cartilage, and the blood and lymph. It has been proposed to distinguish these two forms of mesoderm as mesothelium and mesenchyme respectively , a distinction which is undoubtedly convenient, though probably devoid of the fundamental importance which has been attributed to it by some embryologists. LITERATURE 65 LITERATURE R. Assheton: "The Reinvestigation into the Early Stages of the Development of the Rabbit," Quarterly Journ. of Microsc. Science, xxxvii, 1894. - R. Assheton: "The Development of the Pig During the First Ten Days," Qimrterly Journ. of Micros. Science, xli, 1898. R. Assheton: "The Segmentation of the Ovum of the Sheep, with Observations on the Hypothesis of a Hypoblastic Origin for the Trophoblast," Quarterly Journ. of Microsc. Science, xli, 1898. E.VAN Beneden: "Recherches sur I'embryologie des Mammiferes. De la segmenta- tion, de la formation de la cavit6 blastodermique et de I'embryon didermique chez le Murin," Arch, de Biol., xxvi, 191 1. E. VAN Beneden: "Recherches sur I'embryologie des Mammiferes II: De la ligne primitive, du prolongement cephalique, de la notochorde et du mesoblaste chez le lapin et chez le murin," Arch, de Biol., xxvii, 1912. R. Bonnet: "Beitrage zur Embryologie der Wiederkauer gewonnen am Schafei," Archiv fur Anat. und Physiol., Anat. Ahth., 1884 and 1889., R. Bonnet: "Beitrage zur Embryologie des Hundes," Anat. Hefte, ix, 1897. G. Born: "Erste Entwickelungsvorgange," Ergehnisse der Anat. und Entwicklungs- gesch., I, 1892. E. G. Conklin: "The Cause of Inverse Symmetry," Anatom. Anzeiger, xxiii, 1903. A. C. Eycleshymer: "The Early Development of Amblystoma with Observations on Some Other Vertebrates," Jour, of Morphol., x, 1895. B. Hatschek: "Studien iiber Entwicklung des Amphioxus," Arbeiten aus dem zoolog. Instit. zu Wien, iv, 1881. W. Heape: "The Development of the Mole (Talpa europaea)," Quarterly Journ. of Micros. Science, xxiii, 1883. G. C. Huber: "On the Anlage and Morphogenesis of the Chorda dorsalis in Mam- malia, in particular the Guinea-pig (Cavia Cobaya)". Anat. Record xiv, 1918. A. A. W. Hubrecht: "Studies on Mammalian Embryology II: The Development of the Germinal Layers of Sorex vulgaris," Quarterly Journ. of Microsc. Science, XXXI, 1890. F. Keibel: "Studien zur Entwicklungsgeschichte des Schweines," Morpholog. Arbeiten, iii, 1893. F. Keibel: "Die Gastrulation und die Keimblattbildung der Wirbeltiere," Ergeb- nisse der Anat. und Entwicklungsgesch., x, 1901. M. KuNSEMtJLLER : "Die Eifurchung des Igels (Erinaceus europaeus L.)," Zeitschr. fUr wissensch. Zool., lxxxv, 1906. K. MiTSUKURi and C. Ishikawa: "On the Formation of the Germinal Layers in Chelonia," Quarterly Journ. of Microsc. Science, xxvii, 1887. F. Peebles: "The Location of the Chick Embryo upon the Blastoderm," Journ. of Exper. Zool., i, 1904. E. Selenka: "Studien iiber Entwickelungsgeschichte der Thiere," 4tes Heft, 1886- 87; 5tes Heft, 1891-91. J. Sobotta: "Die Befruchtung und Furchung des Eies der Maus," Archiv fiir mik- rosk. Anat., xlv, 1895. 5 66 LIIERATURE J. Sobotta: "Die Furchung des Wirbelthiereies," Ergehnisse der Anat. und Entwicke- hingsgeschichte, vi, 1897. J. Sobotta: "Neuere Anschauungen Uber Entstehung der Doppel (miss) bild- ungen, mit besonderer Beriicksichtigung der menschlichen Zwillingsgeburten," Wiirzhurger Abhandl., i, 1901. H. H. Wilder: "Duplicate Twins and Double Monsters," Amer. Jour, of Anat., iii, 1904- L. Will: "Beitrage zur Entwicklungsgeschichte der Reptilien," Zoolog. JahrhUcher A hth. fur A nat. , vi, 1 893 . CHAPTER III THE MEDULLARY GROOVE, NOTOCHORD, AND MESO- DERMIC SOMITES In the preceding chapter the development of the mammalian ovum has been described up to and including the formation of the three germinal layers. The earlier stages of development there described are practically unknown in the human ovum, but for the stages subsequent to the establishment of the germinal layers human material is available, and it will, therefore, now be con- venient to consider the structure of the younger human ova at present known and to trace in them the appearance and develop- ment of such structures as the primitive streak, the head process and the gastral mesoderm. The youngest human ovum at present known is that described by Bryce and Teacher, but, unfortunately, it presents certain features that are evidently abnormal, so that it becomes doubtful how far it may be accepted as representing the typical condition. The trophoblast, which was very thick and clearly differentiated into two layers, enclosed a space whose diameter was about 0.63 mm. and which was largely occupied by a loose syncytial tissue. Toward the center of this was an irregular cavity in which were two vesicles, quite separate from one another and probably together representing the embryo, the smaller one being the amniotic cavity and the larger one the cavity lined by the endoderm and known as the yolk-sac (Fig. 37). The separation of these two structures is apparently an abnormality and it is possible that the cavity in which they lie is, as Bryce and Teacher suggest, an artefact pro- duced by contraction of the syncytial tissue during the preserva- tion of the ovum. If comparison of this ovum with those of other mammals is warranted, it may be likened to that of the bat as shown in Fig. 67 68 THE MEDULLARY GROOVE 30, C, with the difference that the space between the primary endo- derm and the trophoblast is greatly enlarged in the human ovum and is occupied by loose syncytial tissue, which may be termed the cellular magma. This condition may be represented diagrammat- ically as in Fig. 39, A, in which the magma is represented as some- what condensed around the amniotic cavity and yolk-sac and upon the inner surface of the trophoblast. Whence this magma tissue Fig. 37.- -From a Reconstruction of the Bryce-Teacher Ovum. ^Bryce-Teacher.) is derived is as yet uncertain, but it seems probable that it repre- sents a precocious development of the extra-embryonic mesoblast, i.e., of that portion of the mesoblast that lies outside the actual limits of the embryonic rudiment (see page 62). Somewhat older are the ova described by Peters, Fetzer, Jung, Linzenmeier and Herzog. The Peters ovum was taken from the uterus of a woman who had committed suicide one calendar month after the last menstruation, and it measured about i mm. in diameter. The entire inner surface of the trophoblast (Fig. $S ce) was lined by a layer of mesoderm {cm), which, on the surface furthest away from the uterine cavity, was considerably thicker THE MEDULLARY GROOVE 69 than elsewhere, forming an area of attachment of the embryo to the wall of the ovum. In the substance of this thickening was the amniotic cavity (am), whose roof was formed by flattened cells,- which, at the sides, became continuous with a layer of columnar cells forming the floor of the cavity and constituting the embryonic ectoderm (ec) . Immediately below this was a layer of mesoderm (m) which split at the edge of the embryonic disk into two layers, one of which became continuous with the mesodermic thickening ^ am^ cm^ .. . .... ^ en J. Fig 38. — Section of Embryo and Adjacent Portion of an Ovum of i mm. am. Amniotic cavity; ce, chorionic ectoderm; cm, chorionic mesoderm; ec, embryonic ectoderm; en, endoderm; m, embryonic mesoderm; ys, yolk-sac. — (Peters.) and so with the layer of mesoderm lining the interior of the tropho- blast, while the other enclosed a sac lined by a layer of endodermal cells and forming the yolk-sac (ys). The total length of the embryo was 0.19 mm., and so far as its ectoderm and mesoderm are concerned it might be described as a flat disk resting on the surface of the yolk-sac, though it must be understood that the yolk-sac also to a certain extent forms part of the embryo. This embryo seems to be in an early stage of the primitive streak formation, before the development of the head process. On 70 THE MEDULLARY GROOVE comparing it with the stage of development represented in Fig. 39, A, it will be seen to present some important advances. The cavity (Fig. 39, B, C,) into which the yolk-sac projects is unrepre- sented in Fig. 39, A, and seems to have been formed by the concen- tration of the cells of the cellular magma upon the trophoblast and around the yolk-sac and amniotic cavity. The cavity is oc- cupied by a mucous fluid, destitute of cellular elements at this stage and forming what is termed the reticular magma, and the size of the human ovum at this stage and later is mainly due to the rapid growth of this cavity. The fact that the cavity is every- ^me Fig. 39. — Diagrams to show the Probable Relationships of the Parts in the Embryos Represented in Pigs. 37 and 38 ac. Amniotic cavity; c, extra-embryonic ccelom; Co, embryonic ccelom; Cy, cyto-tro- phoblast; m, cellular magma; me, chorionic mesoderm; PI, plasmodi-trophoblast; y, yolk sac. where bounded by mesoderm suggests that it is the extra-em- bryonic body-cavity, formed precociously before the splitting of the embryonic mesoderm (see p. 62). It seems more probable, however, that the extra-embryonic ccelom is really represented by certain cavities lined with a flattened epithelium which occur in the immediate neighborhood of the embryo (Figs. 38 and 39, B, Co). These, in later stages, probably become continuous with the cavity occupied by the reticular magma by the breaking down of the separating walls, and if this be the correct interpretation of the THE MEDULLARY GROOVE 71 facts the extra-embryonic coelom is formed precociously in the human ovum and the cavity occupied by the reticular magma eventually becomes part of it. From this stage onward the tro— phoblast and the layer of mesoderm lining it may together be z-^;. %. Fig. 40. — The Embryo v. H. of von Spee. The Left Half of the Chorion has BEEN Removed to show the Embryo. a. Amniotic cavity; h, belly-stalk; ch, chorion; d, yolk-sac; e, extra-embryonic coelom; k, embryonic disk; 2, chorionic villus. — {von Spee.) spoken of as the chorion, the mesoderm layer being termed the chorionic mesoderm. A little older again than the Peters and Herzog ova are those described by Strahl and Beneke, and by von Spee (embryo v. H.), the chorionic cavity of the former two having an average diameter Fig. 41. — Embryo from the Benkkk Ovum, the Roof of the Amniotic Cavity HAVING been Removed. From a model, h, Belly-stalk; p.g., primitive groove; y, yolk-sac. — (Slrahl and Beneke.) of about 2.4 mm., while the corresponding size of the latter two was somewhat less than 4.0 mm. Notwithstanding the considerable increase in the size of these older ova, due to the continued increase in the size of the extra-embryonic coelom, the embryos are but 72 THE MEDULLARY GROOVE little advanced beyond the stage shown by the Peters embryo. The thickening of the chorionic mesoderm that encloses the amni- otic cavity has now become smaller relatively to the extent of the chorion and forms a pedicle, known as the belly-stalk (Fig. 40, h. at the extremity of which is the yolk-sac {d). Furthermore, the amniotic cavity (a) now lies somewhat eccentrically in this pedicle, being near what may be termed its anterior surface, and the entire embryo projects like a papilla from the inner surface of the chorion into the extra-embryonic coelom. Fig. 41 is from a model of the Beneke embryo, detached from the chorion by cutting through the belly-stalk, and with the roof of the amniotic cavity removed. The embryonic disk, thus exposed, is an oval plate, resting, as it were, on the yolk-sac, and quite smooth except for a slight longi- FiG. 42. — Embryo from the Frassi Ovum, the Roof of the Amniotic Cavity HAVING been Removed. From a model. &, belly-stalk; p.g., primitive groove; mg, medullary groove; «. neurenteric canal. — (Frassi.) tudinal groove upon its posterior portion. This is the primitive groove and sections passing through it show the primitive streaky consisting of a sheet of mesoderm interposed between the ectoderm and endoderm, as in the Peters embryo, and but poorly defined from the other two layers. From its anterior edge a median proc- ess extends forward for a short distance and is the head process (see p. 60). In front and to the sides of this there is as yet no mesoderm intervening between the ectoderm and endoderm. The embryonic disk of the Beneke embryo measured 0.75 mm. in length. That of an embryo described by Frassi (Fig. 42) was i.iy^mm. in length, and in correspondence with its greater size, it presents some advances in structure that are of interest. As in THE MEDULLARY GROOVE 73 the younger embryo one sees a distinct primitive groove on the posterior portion of the embryonic disk, but the groove terminates anteriorly at a distinct pore (n), which perforates the disk and opens ventrally into the yolk-sac. This is the neurenteric canal (see p. 6i) and in front of it a groove extends forward in the me- dian line almost to the anterior edge of the embryonic disk and is evidently the first indication of the medullary groove, whose walls are destined to give rise to the central nervous system. Sections passing through the region of the medullary groove show, lying am Fig. 43. — Section through the Prassi Embryo just in Front of the Neuren- teric Canal. am. Amniotic cavity; gm, gastral mesoderm; hp, head process; mp, medullary plate; ys, yolk-sac. — (Frassi.) beneath it, the head process (Fig. 43, hp), already fused with the endoderm (compare p. 61), and on each side of the process is a plate of mesoderm (gm), representing the gastral mesoderm of lower forms (see Figs. 29 and 35), but not as yet showing any indications of splitting into the two layers that bound the embry- onic coelom (see p. 62). This is just beginning to appear in an embryo, also described by von Spee and known as embryo Gle. It measured 1.54 mm. in length and is closely similar, in general appearance, to an embryo described by Eternod and measuring 1.34 mm. in length (Fig. 44). It differs from the Frassi embryo most markedly in that the poste- rior streak region, is bent ventrally so as to lie almost at a right angle with the anterior portion. As a result the belly-stalk arises from the ventral surface of the embryo instead of from its 74 THE MEDULLARY GROOVE Fig. 44. — Embryo 1.34 mm. Long. al, AUantois; am, amnion; bs, belly-stalk; h, heart; m, medullary groove; nc, neurenteric canal; pc, caudal protuberance; ps, primitive streak; ys, yolk-stalk. — {Eternod.) THE MEDULLARY FOLDS 75 posterior extremity, near which the opening of the neurenteric canal (Fig. 43, nc) is now situated, almost the whole length of the surface seen in dorsal view being occupied by the medullary groove (w), which, in the embryo G/e, is bounded laterally by distincT ridges, the medullary folds. In the Kromer embryo Klh (Fig. 45), measuring 1.8 mm. in length, a new feature has made its appearance. The medullary folds have become quite high, and lateral to them there is on each side a series of five or six oblong elevations, which represent what are termed mesodermic somites and are due to divisions of the underlying mesoderm. Fig. 45. — Model of the Kromer Embryo Klh seen from the Dorsal Surface, THE Roof of the Amniotic Cavity having been Removed. — {Keibel and Elze.) Instead of proceeding with a description of the external form of still older embryos it will be convenient to consider the further development of certain structures whose appearance has already been noted, namely, the head process, the medullary folds and the mesodermic somites, and first of all the medullary folds may be considered. The Medullary Folds. — The two folds are continuous ante- riorly, but behind they are at first separate, the anterior portion of the primitive streak lying between them. In forms, such as the Reptilia, which possess a distinct blastopore, this opening lies in the interval between the two, and consequently is in the floor of the medullary groove, and in the mammalia, even though no well-de- fined blastopore is formed, yet at the time of the formation of the 76 THE MEDULLARY FOLDS medullary fold an opening breaks through at the anterior end of the primitive streak in the region of Hensen's node, and places the cavity lying below the endoderm in communication with the space bounded by the medullary folds. The canal so formed is termed the neur enteric canal (Figs. 44 and 46, nc) and is so called because it unites what will later become the central canal of the nervous Pig. 46. — Diagram of a Longitudinal Section through the Embryo Gle, Meas- uring 1.54 MM. IN Length. al, Allantois; am, amnion; B, belly-stalk; ch, chorion; h, heart; nc, neurenteric canal; V, chorionic villi; Y, yolk-sac. — {von Spee.) system with the intestine (enteron) . The significance of this canal has already been discussed (p. 61); it is of very brief persistence, closing at an early stage of development so as to leave no trace of its existence. As development proceeds the medullary folds increase in height and at the same time incline toward one another (Fig. 45), so that their edges finally come into contact and later fuse, the two ecto- THE NOTOCHORD 77 dermal layers forming the one uniting with the corresponding layers of the other (Fig. 47) . By this process the medullary groove becomes converted into a medullary canal which later becomes the central canal of the spinal cord and the ventricles of the brain, the ectodermal walls of the canal thickening to give rise to the central nervous system. The closure of the groove does not, however, take place simultaneously along its entire length, but begins in what corresponds to the neck region of the adult and thence pro- ceeds both anteriorly and posteriorly, the extension of the fusion Fig. 47. — Diagrams showing the Manner ov ihe Closure of the Medullary Groove. taking place rather slowly, however, especially anteriorly, so that an anterior opening into the otherwise closed canal can be distinguished for a considerable period (Fig. 54). The Notochord. — While these changes have been taking place in the ectoderm of the median line of the embryonic disk, modifica- tions of the subjacent endoderm have also occurred. This endo- derm, it will be remembered, was formed by the head process of the primitive streak, and was a plate of cells continuous at the sides with the pimary endoderm and extending forward as far as what will eventually be the anterior part of the pharynx. Along the 78 THE NOTOCHORD line of its junctioD with the primary endoderm it is in relation to the medial edges of the lateral plates of mesoderm, which are comparable to the gastral mesoderm of lower forms, and it itself produces an important embryonic organ known as the notochord or chorda dorsdis, whence the term chorda endoderm sometimes applied to it. I After it has united with the primary endoderm the chorda en- doderm is a flat band, but later it becomes somewhat curved, concave towards the yolk-sack (Fig. 48, A), and, the curvature Fig. 48. — Transverse Sections through Mole Embryos showing the Forma- tion OF the Notochord. ec. Ectoderm; en, endoderm; m, mesoderm; nc, notochord. — (Heape.) increasing, the edges of the plate come into contact and finally fuse (Fig. 48, B), the edges of the primary endoderm at the same time uniting beneath the chordal tube so formed, so that this layer becomes a continuous sheet, as it was at its first appearance. A distinct lumen, the secondary chordal canal, may occur in the the chordal tube, but it is soon obliterated by the enlargement of cells which bound it, and these cells later undergo a peculiar trans- formation whereby the chordal tube is converted into a solid elastic rod surrounded by a cuticular sheath secreted by the cells. The notochord lies at first immediately beneath the median line of the medullary groove, between the ectoderm and the endoderm, and has on either side of it the mesodermal plates. It does not. THE MESODERMIC SOMITES 79 however, quite reach the anterior extremity of the head, but terminates beneath the cerebral portion of the medullary canal at a point just caudad to where the hypophysis will be developed. It is a temporary structure of which only rudiments persist in the~ adult condition in man, but it is a structure characteristic of all vertebrate embryos and persists to a more or less perfect extent in many of the fishes, being indeed the only axial skeleton possessed by Amphioxus. In the higher vertebrates it is almost completely replaced by the vertebral column, which develops around it in a manner to be described later. The Mesodermic Somites. — Turning now to the middle germinal layer, it will be found that in it also important changes take place during the early stages of development. The probable mode of development of the extra-embryonic mesoderm and body cavity has already been described (p. 70) and attention may now be directed toward what occurs in the embryonic mesoderm. In both the Peters embryo and the embryo v. H. described by vonSpee this portion of the mesoderm is represented by a plate of cells lying between the ectoderm and endoderm and continuous at the edges of the embryonic area both with the layer of extra-embryonic meso- derm which surrounds the yolk-sac and, through the mesoderm of the belly-stalk, with the chorionic mesoderm (Fig. 38). In older embryos, such as the embryo Gle of Graf Spee and the younger embryo described by Eternod (Fig. 44), the mesoderm no longer forms a continuous sheet extending completely across the em- bryonic disk, but is divided into two lateral plates, in the interval between which the ectoderm of the floor of the medullary groove and the chorda endoderm are in close contact (Fig. 49) . The cha^iges which next occur have not as yet been observed in the human embryo, though they probably resemble those described in other mammalian embryos, and the phenomena which occur in the sheep may serve to illustrate their probable nature. It has been seen that in the stage represented by the Frassi embryo a plate of mesoderm has formed on either side of the chorda endoderm, and that in a later stage, represented by the Kromer embryo A76, differentiation occurs in these plates leading to the 8o THE MESODERMIC SOMITES formation of mesodermic somites. These make their appearance in what will later be the cervical region of the embryo and their formation proceeds backward as the body of the embryo increases in length. A longitudinal groove appears on the dorsal surface of each lateral plate of mesoderm, marking off the more median thicker portion from the lateral parts (Fig. 49), which from this stage onward may be termed the ventral mesoderm. The median or dorsal portions then become divided transversely into a number of more or less cubical masses which are termed the protovertebrce, or, Fig. 49. — Transverse Section through the Second Mesodermic Somite of Sheep Embryo 3 mm. Long. am, Amnion; en, endoderm; I, intermediate cell-mass; mg, medullary groove; ms, mesodermic somite; so, somatic and sp, splanchnic layers of the ventral mesoderm. • — (Bonnet.) better, mesodermic somites (Fig. 49, ms). The cells of the somites and of the ventral mesoderm, are at first stellate in form, but later become more spindle-shaped, and those near the center of each somite and those of the ventral mesoderm arrange themselves in regular layers so as to enclose cavities which appear in these regions (Fig. 49). Each original lateral plate of gastral mesoderm thus becomes divided longitudinally into three areas, a more median area composed of mesodermic somites, lateral to this a narrow area underlying the original longitudinal groove which separated the somite area from the ventral mesoderm and which from its position is termed the intermediate cell-mass (Fig. 49, /), and, finally, the ventral mesoderm. This last portion is now divided into two lay- ers, the dorsal of which is termed the somatic mesoderm, while the THE MESODERMIC SOMITES 8 1 ventral one is known as the splanchnic mesoderm (Fig. 49, so and sp ; and Fig. 50) , the cavity which separates these two layers being the embryonic body-cavity or pleuro peritoneal cavity (coelom), which will eventually give rise to the pleural, pericardial and peritoneal cavities of the adult as well as the cavity of each tunica vaginalis testis. In the early stages of development this cavity is in wide communication with the extra-embryonic coelom, but later this communication is interrupted (see p. 89). Pig. 50. — Transverse Section of an Embryo of 2.5 mm. (See Pig. 54) showing ON either side of the Medullary Canal a Mesodermic Somite, the Inter- mediate Cell-mass, and the Ventral Mesoderm. — (von Lenhossek.) Beginning in the neck region, the formation of the mesodermic somites proceeds posteriorly until finally there are present in the human embryo thirty-eight pairs in the neck and trunk regions of the body, and, in addition, a certain number are developed in what is later the occipital region of the head. Exactly how many of these occipital somites are developed is not known, but in the cow four have been observed, and there are reasons for believing that the same number occurs in the human embryo. In the lower vertebrates a number of cavities arranged in pairs occur in the more anterior portions of the head and have been homologized 82 THE MESODERMIC SOMITES with mesodermic somites. Whether this homology be perfectly cor- rect or not, these head-cavities, as they are termed, indicate the ex- istence of a division of the head mesoderm into somites, and although practically nothing is known as to their existence in the human embryo, yet, from the relations in which they stand to the cranial nerves and musculature in the lower forms, there is reason to suppose that they are not entirely unrepresented. .^!3^ Fig. si. — Transverse Section of an Embryo of 4.25 mm. at the Level of the Arm Rudiment. A, Axial mesoderm of arm; Am, amnion; il, inner lamella of myotome; M, myo- tome; me, splanchnic mesoderm; ol, outer lamella of myotome; Pn, place of origin of pronephros; 5, sclerotome; S^, defect in wall of myotome due to separation of the sclerotome; st, stomach; Vu, umbilical vein. — (Kollmann.) I'he mesodermic somites in the earliest human embryos in which they have been observed contain a completely closed cavity, and this is true of the majority of the somites in such a form as the sheep. In the four first-formed somites in this^species, however, the somite cavity is at first continuous with the pleuroperitoneal THE MESODERMIC SOMITES 83 cavity and only later becomes separated from it, and in lower vertebrates this continuity of the somite cavities with the general body-cavity is the rule. The somite cavities are consequently to be regarded as portions of the general pleuroperitoneal cavity which have secondarily been separated off. They are, however, of but short duration and early become filled up by spindle-shaped cells derived from the walls of the somites, which themselves under- go a differentiation into distinct portions. The cells of that por- tion of the wall of each somite which is opposite the notochord become spindle-shaped and grow inward toward the median line to surround the notochord and central nervous system, and give rise eventually to the lateral half of the body of a vertebra and the corresponding portion of a vertebral arch. This portion of the somite is termed a sclerotome (Fig. 51, S), and the remainder forms a muscle plate or myotome (M) which is destined to give rise to a portion of the voluntary musculature of the body. The outer wall of the somite has been generally believed to take part in the formation of the cutis layer of the integument and hence has been termed the cutis plate or dermatome, but it seems probable that in mammals, it becomes, transformed into muscular tissue. The intermediate cell-mass in the human embryo, as in lower forms, partakes of the transverse divisions which separate the individual mesodermic somites. From one portion of the tissue in most of the somites (Fig. 51, Pn) the provisional kidneys or Wolffian bodies develop, this portion of each mass being termed a nephrotome, while the remaining portion gives rise to a mass of cells showing no tendency to arrange themselves in definite layers and constituting that form of mesoderm which has been termed mesenchyme (see p. 64). These mesenchymatous masses become converted into connective tissues and blood-vessels. The ventral mesoderm in the neck and trunk regions never becomes divided transversely into segments corresponding to the mesodermic somites, differing in this respect from the other por- tions of the lateral mesoderm. In the head, however, that portion of the middle layer which corresponds to the ventral mesoderm of the trunk does undergo a division into segments in connection 84 THE MESODERMIC SOMITES with the development of the branchial arches and clefts (see p. 93). A consideration of these segments, which are known as the branchiomeres, may conveniently be postponed until the chapters dealing with the development of the cranial muscles and nerves, and in what follows here attention will be confined to what occurs in the ventral mesoderm of the neck and trunk. Its splanchic layer (Fig. 52, vm), applies itself closely to the endodermal digestive tract, which is constricted off from the dorsal portion of the yolk-sac, and becomes converted into mesenchyme out of which the muscular coats of the digestive tract develop. The cells which line the pleuroperitoneal cavity, however, retain their arrangement in a layer and form a part of the serous lining of the peritoneal and other serous cavities, the remainder of the lining being formed by the corresponding cells of the somatic layer; and in the abdominal region the superficial cells, situated near the line where the splanchnic layer passes into the somatic, and in close proximity to the nephrotome of the intermediate cell-mass, be- come columnar in shape and are converted into reproductive cells. The somatic layer, if traced peripherally, becomes continuous at the sides with the layer of mesoderm which lines the outer surface of the amnion (Fig. 51) and posteriorly with the mesoderm of the belly-stalk. T hat portion of it which lies within the body of the embryo, in addition to giving rise to the serous lining of the parietal layer of the pleuroperitoneum, becomes converted into mesenchyme, which for a considerable length of time is clearly differentiated into two zones, a more compact dorsal one which may be termed the somatic layer proper, and a thinner, more ventral vascular zone which is termed the membrana reuniens (Fig. 52). In the earlier stages the somatic layer proper does not extend ventrally beyond the line which passes through the limb buds and it grows out into these buds to form an axial core for them, Iq which later the skeleton of the limb forms. The remain- der of the mesoderm lining the sides and ventral portions of the body-wall is at first formed from the membrana reuniens, but as development proceeds the somatic layer gradually extends more ventrally and displaces, or, more properly speaking, assimilates THE MESODERMIC SOMITES 8s into itself, the membrana reuniens until finally the latter has completely disappeared. It is to be noted that no part of the voluntary musculature of the lateral and ventral walls of the neck and trunk is derived from the somatic layer; it is formed entirely from the myotomes which gradually extend ventrally (Fig. 52) and finally come into contact with their fellows of the opposite side in the mid-ventral line. Whether the voluntary musculature of the limbs is also derived from the myotomes is at present doubtful. It has been very generally believed that the myotomes in their growth ven- trally sent prolongations into the limb buds which invested the Fig, 52. — Diagrams Illustrating the History of the Gastral Mesoderm. dM, dorsal portion of myotome; gr, genital ridge; /, intestine; M, myotome, mr, membrana reuniens; N, nervous system; SC, sclerotome; Sm, somatic mesoderm; vm, splanchnic mesoderm; vM, ventral portion of myotome; Wd, Wolffian duct. axial core of mesenchyme and eventually gave rise to the voluntary muscles. The actual existence of the prolongations of the myo- tomes and their conversion into the limb musculature has, how- ever, not yet been observed and it is quite probable that the limb musculature may be derived from the axial core of somatic meso- derm from which the limb skeleton develops. The appearance of the mesodermic somites is an important phenomenon in the development of the embryo, since it influences fundamentally the future structure of the organism. If each pair 86 THE MESODERMIC SOMITES of mesodermic somites be regarded as a structural unit and termed a metamere or segment, then it may be said that the body is com- posed of a series of metameres, each more or less closely resembling its fellows, and succeeding one another at regular intervals. Each somite differentiates, as has been stated, into a sclerotome and a myotome, and, accordingly, there will primarily be as many verte- brae and muscle segments as there are mesodermic somites, or, in other words, the axial skeleton and the voluntary muscles of the trunk are primarily metameric. Nor is this all. Since each metamere is a distinct unit, it must possess its own supply of nutri- tion, and hence the primary arrangement of the blood-vessels is also metameric, a branch passing off on either side from the main longitudinal arteries and veins to each metamere. And, further, each pair of muscle segments receives its own nerves, so that the arrangement of the nerves, again, is distinctly metameric. It is to be noted that this metamerism is essentially resident in the dorsal mesoderm, the segmentation shown by structures derived from other embryonic tissues being secondary and asso- ciated with the relations of these structures to the mesodermic somites. The metamerism is most distinct in the neck and trunk regions, and at first only in the dorsal portions of these regions, the ventral portions showing metamerism only after the extension into them of the myotomes. But there is clear evidence that the arrangement extends also into the head, and that a portion of its mesoderm is to be regarded as composed of metameres. It has been seen that in the notochordal region of the head of lower vertebrates mesodermic somites are present, while anteriorly in the praechordal region there are head-cavities which resemble closely the mesodermic somites, and are probably directly com- parable to the somites of the trunk. There is reason, therefore, for believing that the fundamental arrangement of the dorsal mesoderm in all parts of the body is metameric, but though this arrangement is clearly defined in early embryos, it loses distinct- ness in later periods of development. But even in the adult the original metamerism is clearly indicated in the arrangement of the nerves and of parts of the axial skeleton, and careful study LITERATURE 87 frequently reveals indications of it in highly modified muscles and blood-vessels. In the head the development of the branchial arches and clefts produces a series of parts presenting many of the peculiarities of metameres, and, indeed, it has been a very general custom to regard them as expressions of the general metamerism which pre- vails throughout the body. It is to be noted, however, that they are produced by the segmentation of the ventral mesoderm, a structure which in the neck and trunk regions does not share in the general metamerism, and, furthermore, recent observations on the cranial nerves seem to indicate that these branchiomeres cannot be regarded as portions of the head metameres or even as structures comparable to these. They represent, more probably, a second metamerism superposed upon the more general one, or, indeed, possibly more primitive than it, but whose relations can only be properly understood in connection with a study of the cranial nerves. LITERATURE In addition to many of the papers cited in the list at the close of Chapter II, the following may be mentioned: C. R. Bardeen: "The Development of the Musculature of the Body Wall in the Pig, etc.," Johns Hopkins Hosp. Rep., ix, 1900. T. H. Bryce and J. H. Teacher: " Contributions to the Study of the Early Develop- ment and Imbedding of the Human Ovum," Glasgow, 1908. A. C. F. Eternod: "Communication sur un oeuf humain avec embryon excessive- ment jeune," Arch. Hal. de Biologie, xxii, 1895. A. C. F. Eternod: "11 y a un canal notochordal dans I'embryon humain," Anal. Anzeiger, xvi, 1899. A. C. F. Eternod: "Les premiers stades du developpement de I'oeuf humain," Trans. Internal. Congr. Med. London, Sect. I, pt. i, 1913. Fetzer: "Ueber ein durch Operation gewonnenes menschliches Ei das in seiner Entwickelung etwa dem Petersschen Ei entspricht," Verh. Anat. Gesellschaft, XXIV, 1 901. L. Frassi: "Weitere Ergebnisse des Studiums eines jungen menschlichen Eies in situ," Arch.f. mikr. Anat., lxxi, 1908. 0. Grosser: " Ein menschlicher Embryo mit Chordakanal," Anat. Hefte,XLVii, 19 13. W. Heape: "The Development of the Mole (Talpa Europaea)," Quarterly Journ. Micros c. Science, xxvii, 1887. M. Herzog: "A contribution to our Knowledge of the Earliest Known Stages of Placentation and Embryonic Development in Man," Amer. Journ. Anat., ix, 1909. 88 LITERATURE P. Jung: "Beitrage zur fruhesten Eieinbettung beim menschlichen Weibe," Berlin, 1908. F. Keibel: "Zur Entwickelungsgeschichte der Chorda bei Saugern (Meerschein- chen und Kaninchen)," Archiv fur Anat. und Physiol., Anat. Abth., 1889. S. Kaestner: "Ueber die Bildung von animalen Muskelfasern aus dem Urwirbel," Arch, fur Anat. undPhys., Anat. Abth., SuppL, 1890. J. Kollmann: "Die Rumpfsegmente menschlicher Embryonen von 13 bis 35 Urwir- beln," Archiv fiir Anat. und Physiol., Anat. Abth., 1891. Linzenmeier: "Ein junges menschliches Eies in situ," -4f<;//. /«> G'>'Mflf^, cii, i9i4> H. Peters: "Ueber die Einbettung des menschlichen Eies und das fruheste bisher bekannte menschliche Placentarstadium," Leipzig und Wien, 1899. F. Graf von Spee: " Beobachtungen an einer menschlichen Keimscheibe mit offener Medullarrinne und Canalis neurentericus," Arch.f. Anat. u. Phys., Anat. Abth., 1889. F. Graf von Spee: "Ueber friihe Entwicklungsstufen des menschlichen Eies," Arch. f. Anat. u. Phys., Anat. Abth., 1896. H. Strahl and R. Beneke: "Ein junger menschlicher Embryo," Wiesbaden, 1910. J. W. VAN Wijhe: "Ueber die Mesoderm segmente des Rumpfes und die Entwick- lung des Excretionsystems bei Selachiern," Archiv fiir mikrosk. Anat., xxxiii, 1889. K. W. Zimmermann: "Ueber Kopfhohlenrudimente beim Menschen," Archiv fiir mikrosk. Anat., Liii, 1898. CHAPTER IV THE DEVELOPMENT OF THE EXTERNAL FORM OF THE HUMAN EMBRYO In the preceding chapter descriptions have been given of human embryos representing the earHer known stages and the development of the general form of the human embryo has been traced up to the time when the mesodermic somites have made their appearance. It will now be convenient to continue the his- tory of the general development up to the stage when the embryo becomes a fetus. In the earlier stages, that is to say up to that represented by the Eternod embryo (Fig. 44), the embryonic disk may be de- scribed as floating upon the surface of the yolk-sac, and while this description still holds good for the Eternod embryo a distinct groove may be seen in that embryo between the peripheral portions of the embryonic disk and the upper part of the sac. This groove*" marks the beginning of the separation or constriction of the em- bryo from the yolk-sac, the result of which is the transformation of the discoidal embryonic portion of the embryonic disk into a cylindrical structure. Primarily this depends upon the deepening of the furrow which surrounds the embryonic area, the edges of this area being thus bent in on all sides toward the yolk-sac. This bending in proceeds most rapidly at the anterior end of the body, as shown in the diagrams (Fig. 53), and less rapidly at the pos- terior end where the belly-stalk is situated, and produces a con- striction of the yolk-sac, the portion of this structure nearest the embryonic disk becoming enclosed within the body of the embryo to form the digestive tract, while the remainder is converted into a pedicle-like portion, the yolk-stalk, at the extremity of which is the yolk-vesicle. The further continuance of the folding in of the edges of the embryonic area leads to an almost complete closing 89 go DEVELOPMENT OF EXTERNAL FORM in of the embryonic coelom and reduces the opening through which the yolk-stalk and belly-stalk communicate with the embryonic tissues to a small area known as the umbilicus. In the Kromer embryo Klb (Fig. 45) this separation of the embryo proper from the yolk-sac has proceeded to such an extent that both extremities of the embryonic disk are free from the yolk- sac, and the anterior extremity is bent ventrally almost at a right angle to the rest of the disk, producing what is termed the vertex bend, sl feature characteristic of all later embryos. The marked Fig. S3. — Diagrams Illustrating the Constriction of the Embryo from the Yolk-sac. A and C are longitudinal, and B and D transverse sections. B is drawn to a larger scale than the other figures. development in this embryo of the medullary folds and the occur- rence of mesodermic somites have already been mentioned (p. 75). Somewhat more advanced is the Bulle embryo described by Kollmann and shown from the side and dorsally in Fig. 54, the greater part of the yolk-sac having been removed as well as the most of the amnion. The embryo measured about 2.5 mm. in length and showed a considerable increase in the number of meso- dermic somites, there being about fourteen of them on either side. Posteriorly the medullary groove has become converted into a medullary canal by the medullary folds meeting over it and fusing, DEVELOPMENT OF EXTERNAL FORM 91 but anteriorly it is still open. The vertex bend is well marked and immediately behind the tip of the head, on the ventral surface of the body, there may be seen a well-marked depression, the oral fossa, between which and the anterior surface of the yolk-sac is a am-<: Fig. 54. — Embryo 2.5 mm. Long. am. Amnion; B, belly-stalk; h, heart; M, closed, and M', still open portions of the medullary groove; Om, vitelline vein; OS, oral fossa; Y, yolk-sac. — (Kollmann.) g rounded elevation due to the formation of the heart. Attention may be called to the fact that the position of this organ is far forward of that which it will eventually occupy, so that it must undergo a marked retrogression during later development. 92 DEVELOPMENT OF EXTERNAL FORM Pig. 55.-^Embryo Lr, 4.2 mm. Long. am, Amnion; au, auditory capsule; B, belly-stalk; h, heart; LI, lower, and ul, upper limb; Y, yolk-sac. — (His.) DEVELOPMENT OF EXTERNAL FORM 93 As an example of a later stage of development the embryo Lr of His, measuring 4.2 mm. in length, may be taken (Fig. 55). In this the constriction of the yolk-sac has progressed so far that its proximal portion may now be spoken of as the yolk-stalk. The mesodermic somites have undergone a further increase and have almost reached their final number, the vertex bend has become still more pronounced and the medullary groove, throughout its entire length, has been converted into the medullary canal, which, anteriorly, shows distinct enlargements and constrictions which foreshadow various portions of the future brain. The auditory organ, which made its appearance in earlier stages, has now become quite distinct, and a lateral bulging of the most anterior portion of the head indicates the position of the future eye. In addition certain other important features have now ap- peared. Thus, about' opposite the heart a second bend, the nape bend, is becoming visible on the dorsal surface of the body and toward the posterior end a distinct sacral bend is evident. Sec- ondly, a little posterior to the level of the nape bend a slight elevation is to be seen on the side of the body; this is the limb bud for the upper limb and a corresponding, though smaller, elevation in the region of the sacral bend represents the lower limb. Thirdly, three grooves having a dorso-ventral direction have appeared on the sides of what will be the future pharyngeal region. These are representatives of a series of branchial clefts, structures that are of great morphological importance in the further develop- ment inasmuch as they determine to a large extent the arrange- ment of various organs of the head region. They represent the clefts which exist in the walls of the pharynx in fishes, through which water, taken in at the mouth, passes to the exterior, bathing on its way the gill filaments attached to the bars or arches, as they are termed, which separate successive clefts. Hence the name ''branchial" which is appHed to them, though in the mam- mals they never have respiratory functions to perform, but, ap- pearing, persist for a time and then either disappear or are applied to some entirely different purpose. Indeed, in man they are never really clefts but merely grooves, and corresponding to each groove 94 DEVELOPMENT OF EXTERNAL FORM in the ectoderm there is also one in the subjacent endoderm of what will eventually be the pharyngeal region of the digestive tract, so that in the region of each cleft the ectoderm and endo- derm are in close relation, being separated only by a very thin layer of mesoderm. In the intervals between successive clefts a more considerable amount of mesoderm is present (Fig. 56). In the human embryo four clefts and five branchial arches develop on each side of the body, the last arch lying posteriorly to the fourth Fig. 56.-FL00R OF THE Pharynx cleft and not being very sharply de- OF Embryo b. 7 mm. Long. fined along its posterior margin. Ep, Epiglottis; Sp, sinus praecer- vicalis; t\ tuberculum impar; t^ As just Stated, the clefts are nor- posterior portions of the tongue; j^^Uy merely grooves, and in later /. II, III, and IV, branchial J < ^ -^u j- arches.— (His.) development either disappear or are converted into special structures. Occasionally, however, a cleft may persist and the thin membrane which forms its floor may become perforated so that an opening from the exterior into the pharynx occurs at the side of the neck, forming what is termed a branchial fistula. Such an abnormality is most fre- quently developed from the lower (ventral) part of the first cleft; normally this disappears, the upper portion of the cleft persisting, however, to form the external auditory meatus and tympanic cavity. A further stage in the differentiation of these clefts and arches is shown by the embryo represented in Fig. 57. The nape bend has now increased to such an exent that the whole anterior part of the body is bent at a right angle to the middle part and the entire embryo is coiled in a spiral manner. The limb buds are much more distinct than in the previous stage and four branchial arches are now present; the second and third have become more defined and a strong process has developed from the dorsal part of the anterior border of the first one, which has thus become somewhat A-shaped. The anterior limb of each A is destined to give rise to the upper jaw, and hence is known as the maxillary process, while the posterior limb represents the future lower jaw and is termed the mandibular process. DEVELOPMENT OF EXIERNAL FORM 95 In the stage represented by this embryo the closing in of the embryonic ccelom has progressed to such a degree that only a small opening is left in the ventral body- wall of the embryo through which the yolk-stalk and its accompanying vessels and the belly-stalk pass. Indeed the margins of the umbilicus may have begun to be prolonged outward over these structures, enclosing them in a cylindrical investment, the first stage of what will later be the umbilical cord being thus established. Fig. 57. — Embryo Backer 7.3 mm. in Length. X 5. — {Keihel and Elze.) Leaving aside for the present all consideration of the further development of the limbs and branchial arches, the further evolu- tion of the general form of the body may be rapidly sketched. In an embryo (Fig. 58) from Ruge's collection, described and figured by His and measuring 9.1 mm. in length,* the prolongation of the * This measurement is taken in a straight line from the most anterior portion of the nape bend to the middle point of the sacral bend and does not follow the curva- ture of the embryo. It may be spoken of as the nape-rump length and is convenient for use during the stages when the embryo is coiled upon itself. 96 DEVELOPMENT OF EXTERNAL FORM margins of the umbilicus has increased until more than half the yolk-stalk has become enclosed within the umbilical cord. The nape and sacral bends are still very pronounced, although the em- bryo is beginning to straighten out and is not quite so much coiled as in the preceding stage. At the posterior end of the body there has developed a rather abruptly conical tail filament, in the place of Fig. 58. — Embryo 9.1 mm. Long. LI, Lower limb; U, umbilical cord; Ul, upper limb; Y, yolk-sac- ■{His.) the blunt and gradually tapering termination seen in earlier stages, and a well-marked rotundity of the abdomen, due to the rapidly increasing size of the liver, begins to become evident. In later stages the enclosure of the yolk- and belly-stalks within the umbilical cord proceeds until finally the cord is complete through the entire interval between the embryo and the wall of the ovum. At the same time the straightening out of the embryo continues, as may be seen in Fig. 59 representing the embryo xlv DEVELOPMENT OP EXTERNAL FORM 97 (Br2) of His, which shows also, both in front of and behind the neck bend, a distinct depression, the more anterior being the occipital and the more posterior the nape depression; both these depressions are the indications of changes taking place in the central nervous system. The tail filament has become more marked, and in the head region a slight ridge surrounding the eyeball and marking out the conjunctival area has appeared; a depression anterior to the nasal fossae marks off the nose from the forehead ; and the external ear, whose development will be consid- FiG. 59. — Embryo Br2, 13.6 mm. Long. — (His.) ered later on, has become quite distinct. This embryo had a nape-rump length of 13.6 mm. In the embryos S2 and L3 (Fig. 60, A and B) of His' collection the straightening out of the nape bend is proceeding, and indeed is almost completed in embryo L3, which begins to resemble closely the fully formed fetus. The tail filament, somewhat reduced in size, still persists and the rotundity of the abdomen continues to be well marked. The neck region is beginning to be distinguishable in embryo S2 and in embryo L3 the eyelids have appeared as slight folds surrounding the conjunctival area. The nose and forehead are clearly defined by the greater development of the nasal groove 98 DEVELOPMENT OF EXTERNAL FORM and the nose has also become raised above the general surface of the face, while the external ear has almost acquired its final fetal form. These embryos measure respectively about 15 and 17.5 mm. in length.* Finally, an embryo — again one of those described by His, namely, his Wt, having a length of 23 mm. — may be figured (Fig. 61) as representing the practical acquisition of the fetal Pig. 60. -A, Embryo S2, 15 mm. Long (showing Ectopia of the Heart); B, Embryo L2, 17.5 mm. Long. — {His.) form. This embryo dates from about the end of the second month of pregnancy, and from this period onward it is proper to use the term fetus rather than that of embryo. The changes which have been described in preceding stages are now complete and it remains only to be mentioned that the caudal filament, which is still prominent, gradually disappears in later stages, becoming, as it were, submerged and concealed beneath adjacent parts by the development of the buttocks. The incompleteness * The embryo S2 presents a slight abnormality in the great projection of the heart, but otherwise it appears to be normal. DEVELOPMENT OF THE BRANCHIAL ARCHES 99 of the development of these regions in embryo Wt is manifest, not only from the projection of the tail filament, but also from the external genitalia being still largely visible in a side view of the- embryo, a condition which will disappear in later stages. Pig. 6i. — Embryo Wt, 23 mm. Long. — (His.) The Later Development of the Branchial Arches, and the Development of the Face. — In the embryo shown in Fig. 57, the four branchial clefts and five arches which develop in the human embryo are visible in surface view^s^ but in^ the Euge embryo (Fig. 58) it will be noticed t-i^t qnly^the firt^t two arches, the first with a well-developed maxillary process, and the cleft separating them can be distinguished. Tllis ii diie to'b sinti>ig ihw^id of the region occupied by the tKiee posterior arches so that a triangular depres- lOO DEVELOPMENT OF THE BRANCHIAL ArCHES sion, the sinus prcBcervicalis, is formed on each side of what will later become the anterior part of the neck region. This is well shown in an embryo (Br2) described by His which measured 6.9 mm. in length and of which the anterior portion is shown in Fig. 62. The anterior boundary of the sinus (ps) is formed by the posterior edge of the second arch and its posterior boundary by the thoracic wall, and in later stages these two boundaries gradu- ally approach one another so as first of all to diminish the opening into the sinus and later to completely obliterate it by fusing to- pic. 62. — Head of Embryo of 6.9 mm. na. Nasal pit; ps, praecervical sinus. — (His.) gether, the sinus thus becoming converted into a completely closed cavity whose floor is formed by the ectoderm covering the three posterior arches and the clefts separating these. This cavity eventually undergoes degeneration, no traces of it occurring nor- mally in the ad«ltf, although certain cysts occasionally observed in the sides of th&nfcl;»may rj^iesent .p^rsjstipg portions of it. A somewhat aimijar process results in tke clgsure of the ventral portion of the first del t,* a fold grov;ing backward from the pos- * See page 94, small type. DEVELOPMENT OF THE BRANCHIAL ARCHES lOI terior edge of the j&rst arch and fusing with the ventral part of the anterior border of the second arch. The upper part of the cleft persists, however, and, as already stated, forms the external auditory meatus, the pinna of the ear being developed from the adjacent parts of the first and second arches (Figs. 59 and 60). The region immediately in front of the first arch is occupied by a rather deep depression, the oral fossa, whose early develop- ment has already been noticed. In an embryo measuring 8 mm. Fig. 63. — Face of Embryo of 8 mm. mxp. Maxillary process; np, nasal pit; os, oral fossa; pg, processus globularis. — {His. in length (Fig. 63) the fossa {os) has assumed a somewhat irregular quadrilateral form. Its posterior boundary is formed by the mandibular processes of the first arch, while laterally it is bounded by the maxillary processes {mxp) and anteriorly by the free edge of a median plate, termed the nasal process, which on either side of the median line is elevated to form a marked protuberance, the processus globularis {pg). The ventral ends of the maxillary processes are widely separated, the nasal process and the proc- essus globulares intervening between them, and they are also separated from the globular processes by a deep and rather wide groove which anteriorly opens into a circular depression, the nasal pit {np). 102 DEVELOPMENT OF THE FACE Later on the maxillary and globular processes unite, obliterat- ing the groove and cutting off the nasal pits — which have by this time deepened to form the nasal fossae — from direct communica- tion with the mouth, with which, however, they later make new communications behind the maxillary processes, an indication of the anterior and posterior nares being thus produced. Fig. 64. — Pace of Embryo after the Completion of the Upper Jaw. — (His.) Occasionally the maxillary and globular processes fail to unite on one or both sides, producing a condition popularly known as "harelip." At the time when this fusion occurs the nasal fossae are widely separated by the broad nasal process (Fig. 64), but during later development this process narrows to form the nasal septum and is gradually elevated above the general surface of the face as shown in Figs. 59-61. By the narrowing of the nasal process the globular processes are brought nearer together and form the por- tions of the upper jaw immediately on each side of the median DEVELOPMENT OF THE LIMBS I03 line, the rest of the jaw being formed by the maxillary processes. In the meantime a furrow has appeared upon the mandibular process, running parallel with its borders (Fig. 60) ; the portion o£ the process in front of this furrow gives rise to the lower lip and is known as the lip ridge, while the portion behind the furrow be- comes the lower jaw proper and is termed the chin ridge. The Development of the Limbs. — As has been already pointed out, the limbs make their appearance in an embryo measuring about. 4 mm. in length (Fig. 55) and are at first bud-like in form. As they increase in length they at first have their long axes directed parallel to the longitudinal axis of the body and become somewhat flattened at their free ends, remaining cylindrical in their proximal portions. A furrow or constriction appears at the junction of the flattened and cylindrical portions (F%. 58), and later a second con- struction divides the cylindrical portion into a proximal and distal moiety, the three segments of each limb — the arm, forearm, and hand in the upper limb, and the thigh, leg, and foot in the lower — being thus marked out. The digits are first indicated by the de- velopment of four radiating shallow grooves upon the hand and foot regions (Fig. 59), and a transverse furrow uniting the proximal ends of the digital furrows indicates the junction of the digital and palmar regions of the hand or of the toes and body of the foot. After this stage is reached the development of the upper limb proceeds more rapidly than that of the lower, although the processes are essentially the same in both limbs. The digits begin to project slightly, but are at first to a very considerable extent united together by a web, whose further growth, however, does not keep pace with that of the digits, these thus coming to project more and more in later stages. Even in comparatively early stages the thumb, and to a somewhat slighter extent the great toe, is widely separated from the second digit (Figs. 60 and 61). While these changes have been taking place the entire limbs have altered their position with reference to the -axis of the body, being in stages later than that shown in Fig. 58 directed ventrally so that their longitudinal axes are at right angles to that of the I04 DEVELOPMENT OF THE LIMBS body. From the figures of later stages it may be seen that it is the thumb (radial) side of the arm and the great toe (tibial) side of the leg which are directed forward; the plantar and palmar surfaces of the feet and hands are turned toward the body and the elbow is directed outward and slightly backward, while the knee looks outward and slightly forward. It seems proper to conclude that the radial side of the arm is homologous with the tibial side of the leg, the palmar surface of the hand with the plantar surface of the foot, and the elbow with the knee. The limbs are not yet, however, in their final position but must undergo a second alteration, whereby their long axes again become parallel with that of the body. This is accomplished by a rotation of the limbs around axes passing through the shoulder- and hip- joints, together with a rotation about their longitudinal axes through an angle of 90 degrees. This axial rotation of the upper limb is, however, in exactly the opposite direction to that of the lower limb of the corresponding side, so that the homologous surfaces of the two limbs have entirely different relations, the radial side of the arm, for instance, being the outer side while the tibial side of the leg is the inner side, and whereas the palmar sur- face of the hand looks ventrally, the plantar surface of the foot looks dorsally. In making these statements no account is taken of the sec- ondary position which the hand may assume as the result of its pronation; the positions given are those assumed by the limbs when both the bones of their middle segment are parallel to one another. It may be pointed out that the prevalent use of the physiological terms flexor and extensor to describe the surfaces of the limbs has a tendency to obscure their true morphological relationships. Thus if, as is usual, the dorsal surface of the arm be termed its extensor surface, then the same term should be applied to the entire ventral surface of the leg, and all movements of the lower limb ventrally should be spoken of as movements of extension and any movement dorsally as movements of flexion. And yet a ventral movement of the thigh is generally spoken of as a flexion of the hip-joint, while a straightening out of the foot upon the leg — that is to say, a movement of it dorsally — is termed its extension. AGE OF EMBRYO AT DIFFERENT STAGES I05 The Age of the Embryo at Different Stages. — The age of an embryo is a matter of considerable moment to the embryologist who desires to trace the successive stages in the development of any organ. In the case of the human embryo an exact determina- tion of the age is somewhat difficult, since in the majority of cases the only available datum from which it may be estimated is the time of the cessation of the menses. From what has already been said (pp. 28, 37) it is evident that this menstruation age (Mall) can only be approximative to the actual age, which should date from the moment of fertilization. The available evidence (see p. 28) indicates that ovulation takes place at some time in the inter- menstrual period, on the average about the middle of its duration, but since this duration is about two weeks the limits of variation from the average must be quite large, too large to be of much value in the case of young embryos, where a day means much. The earlier attempts at estimating the ages of young human embryos, those of His for instance, were based on the belief that ovulation took place as a rule immediately before menstruation, and if fertilization occurred the menses were omitted. On this basis His estimated embryos of 2.2 to 3.0 mm. to be two to two and a half weeks old, those of 5.0 to 6.0 mm. to be about three and one-half weeks and those of lo.o to ii.o mm. to be about four and one-half weeks. It is certain, however, that such ages are decidedly too low, perhaps by as much as a week. A small number of cases are on record in which the date of the coition that led to the pregnancy is definitely known. This copulation age does not necessarily give the exact fertilization age, but it is probably within one, or at most two, days of it (see p. 36). The Bryce-Teacher ovum, with an embryo measuring 0.15 mm. in length, was the result of a coition that took place 16 days before the ovum was aborted, and the assumption that the embryo was about two weeks old cannot be far astray. Similarly an embryo described by Eternod and measuring 1.3 mm. in length was the result of a single coition occurring twenty-one days previously and its age may be set at approximately three weeks or better at eighteen or nineteen days. A later embryo which measured 2 5 mm . io6 AGE OF EMBRYO AT DIFFERENT STAGES crown-rump measurement, was the result of a coition that took place fifty-six days before the abortion, so that the embryo may be regarded as having been a httle less than eight weeks old. These and three other similar cases may be shown in a table thus : Length of Emb. Menstruation Copulation Probable Fertiliza- Authority in mm. Age in Days Age in Days tion Age in Days About o.is 38 16 14 Bryce-Teacher 1.3 34 21 19 Eternod V. B. 8.8 42 38 36 Tandler V. B. 14.0 65 47 45 Rabl V. B. 18.0 54 47 45 Mall V. B. 25.0 75 56 54 Mall In the fourth column two days have been taken from the copulation age to estimate the fertilization age. This may be too much in some cases and too little in others and either this or a difference in the rate of growth may account for the fact that two embryos differing in their vertex-breech measurements by 4.0 mm. appear to be of the same age. The 14.0 mm. embryo, how- ever, might be assigned a fertilization age of 44 days and the 18.0 mm. one an age of 46 days without any violation of the data. It is interesting to note the wide variation that obtains between the menstruation and copulation ages, the difference in one case being as little as four days and in another as much as twenty-two, though the average difference as determined from statistics of full-term births is about eleven days. Making all possible corrections the exact age cannot be de- termined within less than two or three days (Mall) , but in general one may say that embryos of 2.0 to 3.0 mm. may be assigned to the fourth week of development, those of 5.0 to 6.0 vertex-breech length to the latter part of the fifth week, those of 10. o mm. to the end of the sixth week and those of 25.0 to 28.0 mm. which are just passing into the fetus stage, to the end ot the eighth week. As regards the later periods of development, the limits of error for any date become of less importance. Schroder gives the following measurements as the average : LITERATURE I07 3d lunar month 70-90 mm. 4th lunar month 100-170 mm. 5th lunar month 180-270 mm. 6th lunar month 280-340 mm. _ 7th lunar month 35«>~38o mm. 8th lunar month 425 mm. Qth lunar month 467 mm. loth lunar month 490-500 mm. The data concerning the weight of embryos of different ages are as yet very insufficient, and it is well known that the weights of new-born children may vary greatly, the authenticated ex- tremes being, according to Vierordt, 717 grams and 6123 grams. It is probable that considerable variations in weight occur also during fetal life. So far as embryos of the first two months are concerned, the data are too imperfect for tabulation; for later periods Fehling gives the following as average weights : 3d month 20 grams. 4th month 120 grams. 5th month 285 grams. 6th month 635 grams. 7th month 1220 grams. 8th month 1700 grams. 9th month 2240 grams. loth month 3250 grams. and the results obtained by Jackson are essentially similar. LITERATURE In addition to the papers of Bryce and Teacher, Eternod, Fetzer, Frassi, Herzog, Peters, Von Spee, Strahl and Beneke and Grosser, cited in the preceding chapter, the following may be mentioned: J. L. Bremer: "Description of a 4 mm. Human Embryo," Amer. Journ. Anat., V, 1906. J. Broman: "Beobachtung eines menschlichen Embryos von beinahe 3 mm. Lange mit specieller Bemerkung Uber die bei demselben befindlichen Hirnfalten," Morpholog. Arheiten, v, 1895. A. J. P. VAN DEN Broek: "Zur Kasuistik junger menschlicher Embryonen," Anat. Hefie, XLJY, 191 1. J._M. Coste: ''Histoire g^nerale et particuliere du developpement des corps organ- ises," Paris, 1 847-1 859. W. E. Dandy: "A Human Embryo with Seven Pairs of Somites, Measuring about 2 mm. in Length," Amer. J&iirn. Anat.,x, 1910. Io8 LITERATURE A. Ecker: "Beitrage zur Kenntniss der ausserer Formen jiingster menschlichen Embryonen," Archiv. fur Anat. und Physiol., Anat. Abth., 1880. C. Elze: " Beschreibung eines menschlichen Embryos von zirka 7 mm. grosster Lange," Anat. Hefie, xxxv, 1907. C. GiACOMiNi: **Un oeuf humain de 11 jours," Archives Ital. de Biologie, xxxrx, 1898. O. Grosser: "Altersbestimmung junges menschliche Embryonen — Ovulations — und Menstruationstermin," Anat. Anzeiger, xlvii, 1914. V. Hensen: "Beitrag zur Morphologic der Korperform und des Gehirns des menschlichen Embryos," Archiv fiir Anat. und Physiol., Anat. Abth., 1877. W. His: " Anatomie menschlicher Embryonen," Leipzig, 1880. F. Hochstetter: "Bilder der ausseren Korperform einiger menschlicher Embryo- nen aus den beiden Ersten Monaten der Entwicklung," Munich, 1907. N. W. Ingalls: " Beschreibung eines menschlichen Embryos von 4,9 mm.," Arch. fiir mikr. Anat., lxx, 1907. C. M. Jackson: "On the Prenatal Growth of the Human Body and the Relative Growth of the Various Organs and Parts," Amer, Journ. Anat., ix, 1909. J. Janosik: "Zwei junge menschliche Embryonen," Archiv fiir mikrosk. Anat., xxx, 1887. H. E. Jordan: "Description of a 5 mm. Human Embryo," Anat. Record, iii, 1909. P. Jung: "Beitrage zur friihesten Ei-einbettung beim menschlichen Weibe," Berlin, 1908. F. Keibel: "Ein sehr junges menschliches Ei," Archiv fiir Anat. und Physiol., Anat. Abth., 1890. F. Keibel: "Ueber einen menschlichen Embryo von 6.8 mm. grosster Lange," Verhandl. Anatom. Gesellsch., xiii, 1899. F. Keibel and C. Elze: "Normentafeln zur Entwicklungsgeschichte der Wirbel- tiere," Heft viii, 1908. J. Kollmann: "Die Korperform menschlicher normaler und pathologischer Em- bryonen," Archiv fiir Anat. und Physiol., Anat. Abth., Supplement, 1889. A. Low: "Description of a Human Embryo of 13-14 Mesodermic Somites," Journ. Anat. and Phys., xlii, 1908. F. P. Mall: "A Human Embryo Twenty-six Days Old," Journ. of Morphology, v, 1891. F. P. Mall: "A Human Embryo of the Second Week," Anat. Anzeiger^ viii, 1893. F. P. Mall: " Early Human Embryos and the Mode of their Preservation," Bulletin of the Johns Hopkins Hospital, iv, 1894. F. P. Mall: "On the Age of Human Embryos," Amer. Journ. Anat., xxiii, 1918. C. S. Minot: "Human Embryology," New York, 1892. J. MtJLLER: " Zerglierderungen menschlicher Embryonen aus friiherer 2^it," Archiv fiir Anat. und Physiol., 1830. C. PmsALix: "Etude d'un Embryon humain de ii millimeters," Archives de zoolog. experimentale et generate, S6r. 2, VI, 1888. H. Piper: "Ein menschlicher Embryo von 6.8 mm. Nackenlinie," Archiv fiir Anat. und Physiol., Anal. Abth., 1898. C. Rabl: "Die Entwicklung des Gesichtes, Heft i. Das Gesicht der Saugetiere, Leipzig, 1902. LITERATURE IO9 G. Retzius: "Zur Kenntniss der Entwicklung der Korperformen des Menschen wahrend der fotalen Lebensstufen," Biolog. Untersuch., xi, 1904. J. Tandler: "Ueber einen menschlichen Embryo von 38 Tage," AnaL Anzeiger, XXXI, 1907. Allen Thompson: "Contributions to the History of the Structure of the Human Ovum and Embryo before the Third Week after Conception, with a Description of Some Early Ova," Edinburgh Med. and Surg. Journal, iii, 1839. (See also Froriep's Neue Notizen, xiii, 1840). P. Thompson: Description of a human embryo of twenty-three paired somites," Journ. Anat. and Phys.,XLi, 1907. F. W. Thyng: "The Anatomy of a 17.8 mm. human embryo," Amer. Journ. Anat., XVII, 1914. H. Triepel: "Altersbestimmung bei menschlichen Embryonen," Anal. Anz., XLVI, 1914. H. Triepel: "Alter menschlicher Embryonen und Ovulationstermin," Anal. Anzei- ger, XLViii, 1915. I. E. Wallin: "A Human Embryo of Thirteen Somites," Amer. Journ. AnaL, xv, 1913- J. C. Watt: "Description of two young twin human embryos with 17-19 paired somites," Puh. Carnegie Inst. No. 222, Contr. to Embryol, No. 2, 1915. CHAPTER V THE YOLK-STALK, BELLY-STALK, AND FETAL MEMBRANES The conditions to which the embryos and larvae of the majority of animals must adapt themselves are so different from those under which the adult organisms exist that in the early stages of de- velopment special organs are very frequently developed which are of use only during the embryonic or larval period and are dis- carded when more advanced stages of development have been reached. This remark applies with especial force to the human embryo which leads for a period of nine months what may be termed a parasitic existence, drawing its nutrition from and yielding up its waste products to the blood of the parent. In order that this may be accomplished certain special organs are developed by the embryo, by means of which it forms an intimate connection with the walls of the uterus, which, on its part, be- comes greatly modified, the combination of embryonic and ma- ternal structures producing what are termed the deciducB, owing to their being discarded when at birth the parasitic mode of life is given up. Furthermore, it has already been seen that many peculiar modifications of development in the human embryo result from the inheritance of structures from more or less remote ancestors, and among the embryonic adnexes are found structures which represent in a more or less modified condition organs of con- siderable functional importance in lower forms. Such structures are the yolk-stalk and vesicle, the amnion, and the allantois, and for their proper understanding it will be well to consider briefly their development in some lower form, such as the chick. At the time when the embryo of the chick begins to be con- stricted off from the surface of the large yolk-mass, a fold, con- IIO YOLK-STALK AND FETAL MEMBRANES III sisting of ectoderm and somatic mesoderm, arises just outside the embryonic area, which it completely surrounds. As develop- ment proceeds the fold becomes higher and its edges gradually draw nearer together over the dorsal surface of the embryo (Fig. 65, A, Af), and finally meet and fuse (Fig. 65, B and C), so that the embryo becomes enclosed within a sac, which is termed the amnion and is formed by the fusion of the layers which consti- tuted the inner wall of the fold. The layers of the outer wall of the fold after fusion form part of the general ectoderm and somatic Fig. 65. — Diagrams Illustrating the Formation of the Amnion and Allantois IN THE Chick. Af, Amnion folds; Al, allantois; Am, amniotic cavity; Ds, yolk-sac. — (Gegenbaur.) mesoderm which make up the outer wall of the ovum and together are known as the serosa, corresponding to the chorion of the mammalian embryo. The space which occurs between the am- nion and the serosa is a portion of the extra-embryonic coelom, and is continuous with the embryonic pleuroperitoneal cavity. In the ovum of the chick, as in that of the reptile, the proto- plasmic material is limited to one pole and rests upon the large yolk-mass. As development proceeds the germ layers gradu- ally extend around the yolk-mass and eventually completely en- 112 THE AMNION close it, the yolk-mass coming to lie within the endodermal layer, which, together with the splanchnic mesoderm which lines it, forms what is termed the yolk-sac. As the embryo separates from the yolk-mass the yolk-sac is constricted in its proximal portion and so differentiated into a yolk-stalk and a yolk-sac, the contents of the latter being gradually absorbed by the embryo during its growth, its walls and those of the stalk being converted into a portion of the embryonic digestive tract. In the meantime, however, from the posterior portion of the digestive tract, behind the point of attachment of the yolk-sac, a diverticulum has begun to form (Fig. 65, A, Al). This increases in size, projecting into the extra-embryonic portion of the pleuro- peritoneal cavity and pushing before it the splanchnic mesoderm which lines the endoderm (Fig. 65, B and C). This is the allan- tois, which, reaching a very considerable size in the chick and applying itself closely to the inside of the serosa, serves as a respi- ratory and excretory organ for the embryo, for which purpose its walls are richly supplied with blood-vessels, the allantoic arteries and veins. Toward the end of the incubation period both the amnion and allantois begin to undergo retrogressive changes, and just before the hatching of the young chick they become completely dried up and closely adherent to the egg-shell, at the same time separating from their point of attachment to the body of the young chick, so that when the chick leaves the egg-shell it bursts through the dried-up membranes and leaves them behind as useless structures. The Amnion. — Turning now to the human embryo, it will be found that the same organs are present, though somewhat modified either in the mode or the extent of their development. A well developed amnion occurs, arising, however, in a very different manner from what it does in the chick; a large yolk-sac occurs even though it contains no yolk; and an allantois which has no respira- tory or excretory functions is present, though in a somewhat degenerated condition. It has been seen from the description of the earliest stages of development that the processes which occur in the lower forms are greatly abbreviated in the human embryo. THE AMNION II3 The enveloping layer, instead of gradually extending from one pole to enclose the entire ovum, develops in situ during the stages immediately succeeding segmentation, and the extra-embryonic_ mesoderm, instead of growing out from the embryo to enclose the yolk-sac, apparently also undergoes a precocious development in situ. The earliest stages in the development of the amnion are not yet known for the human embryo, but from the condition in which it is found in the Peters embryo (Fig. 38) and in the embryo v.H. of von Spec (Fig. 40) it is probable that it arises, not by the fusion of the edges of a fold, as in the chick, but by a vacuolization of a portion of the inner cell-mass, as has been de- scribed as occurring in the bat (p. 57). It is, then, a closed cavity from the very beginning, the floor of the cavity being formed by the embryonic disk, its posterior wall by the anterior surface of the belly-stalk, while its roof and sides are thin and composed of a single layer of flattened ectodermal cells lined on the outside by a layer of mesoderm continuous with the somatic mesoderm of the embryo and the mesoderm of the belly-stalk (Fig. 66, A). When the bending downward of the peripheral portions of the embryonic disk to close in the ventral surface of the embryo oc- curs, the line of attachment of the amnion to the disk is also carried ventrally (Fig. 66, B), so that when the constriction off of the embryo is practically completed, the amnion is attached anteriorly to the margin of the umbilicus and posteriorly to the extremity of the band of ectoderm lining what may now be con- sidered the posterior surface of the belly-stalk, while at the sides it is attached along an oblique line joining these two points (Fig. 66, B and C, in which the attachment of the amnion is indicated by the broken line) . Leaving aside for the present the changes which occur in the attachment of the amnion to the embryo (see p. 119), it may be said that during the later growth of the embryo the amniotic cavity increases in size until finally its walls come into contact with the chorion, the extra-embryonic body-cavity being thus practically obliterated (Fig. 66, D), though no actual fusion of amnion and chorion occurs. Suspended by the umbilical cord 114 THE AMNION which has by this time developed, the embryo floats freely in the amniotic cavity, which is filled by a fluid, the liquor amnii, whose origin is involved in doubt, some authors maintaining that it in- filtrates into the cavity from the maternal tissues, while others hold that a certain amount of it at least is derived from the em- FiG. 66. — Diagrams Illustrating the Formation of the Umbilical Cord. The heavy black line represents the embryonic ectoderm; the dotted line repre- sents the line of reflexion of the body ectoderm into that of the amnion. Ac, Amniotic cavity; Al, allantois; Be, extra-embryonic coelum; Bs, belly-stalk; Ch, horion; P, placenta; Uc, umbilical chord; V, chorionic villi; Ys, yolk-sac. bryo. It is a fluid with a specific gravity of about 1.003 ^^nd con- tains about I per cent, of solids, principally albumin, grape-sugar, and urea, the last constituent probably coming from the embryo. When present in greatest quantity — that is to say, at about the beginning of the last month of pregnancy — it varies in amount between one-half and three-fourths of a liter, but during the last month it diminishes to about half that quantity. To protect the THE YOLK-SAC II5 epidermis of the fetus from maceration during its prolonged im- mersion in the liquor amnii, the sebaceous glands of the skin at about the sixth month of development pour out upon the surface of the body a white fatty secretion known as the vernix caseosa. During parturition the amnion, as a rule, ruptures as the re- sult of the contraction of the uterine walls and the liquor amnii escapes as the *' waters,*' a phenomenon which normally precedes the delivery of the child. As a rule, the rupture is sufficiently ex- tensive to allow the passage of the child, the amnion remaining behind in the uterus, to be subsequently expelled along with the deciduae. Occasionally it happens, however, that the amnion is sufficiently strong to withstand the pressure exerted upon it by the uterine con- tractions and the child is born still enveloped in the amnion, which, in such cases, is popularly known as the *'caul," the possession of which, according to an old superstition, marks the child as a favorite of fortune. As stated above, the liquor amnii varies considerably in amount in different cases, and occasionally it may be present in excessive quanti- ties, producing a condition known as hydramnios. On the other hand, the amount may fall considerably below the normal, in which case the amnion may form abnormal unions with the embryo, sometimes pro- ducing malformations. Occasionally also bands of a fibrous character traverse the amniotic cavity and, tightening upon the embryo during its growth, may produce various malformations, such as scars, sphtting of the eye lids or lips, or even amputation of a limb. The Yolk-sac. — The probable mode of development of the yolk-sac in the human embryo, and its differentiation into yolk- stalk and yolk-vesicle have already been described (p. 89). When these changes have been completed, the vesicle is a small pyriform structure lying between the amnion and the chorionic mesoderm, some distance away from the extremity of the umbilical cord (Fig. 66, D), and the stalk is a long slender column of cells extending from the vesicle through the umbilical cord to unite with the in- testinal tract of the embryo. The vesicle persists until birth and may be found among the decidual tissues as a small sac measuring from 3 to 10 mm. in its longest diameter. The stalk, however, early undergoes degeneration, the lumen which it at first contains Il6 THE ALLANTOIS AND BELLY-STALK becoming obliterated and its endoderm also disappearing as early as the end of the second month of development. The portion of the stalk which extends from the umbilicus to the intestine usually shares in the degeneration and disappears, but in about 3 per cent, of cases it persists, forming a more or less extensive diverticulum of the lower part of the small intestine, sometimes only half an inch or so in length and sometimes much larger. It may or may not retain connection with the abdominal wall at the umbilicus, and is known as MeckeVs diverticulum. This embryonic rudiment is of no Httle importance, since, when present, it is apt to undergo invagination into the lumen of the small intestine and so occlude it. How frequently this happens relatively to the occurrence of the diverticulum may be judged from the fact that out of one hundred cases of occlusion of the small intestine six were due to an invagination of the diverticulum. In the reptiles and birds the yolk-sac is abundantly supplied with blood-vessels by means of which the absorption of the yolk is carried on, and even although the functional importance of the yolk-sac as an organ of nutrition is almost nil in the human embryo, yet it still retains a well-developed blood-supply, the walls of the vesicle, especially, possessing a rich network of vessels. The future history of these vessels, which are known as the vitelline vessels, will be described later on. The Allantois and Belly-stalk. — It has been seen that in reptilian and avian embryos the allantois reaches a high degree of development and functions as a respiratory and excretory organ by coming into contact with what is comparable to the chorion of the mammalian embryo. In man it is very much modified both in its mode of development and in its relations to other parts, so that its resemblance to the avian organ is somewhat obscured. The differences depend partly upon the remarkable abbreviation manifested in the early development of the human embryo and partly upon the fact that the allantois serves to place the embryo in relation with the maternal blood, instead of with the external atmosphere, as is the case in the egg-laying forms. Thus, the THE ALLANTOTS AND BELLY-STALK TI7 endodermal portion of the allantois, instead of arising from the intestine and pushing before it a layer of splanchnic mesoderm to form a large sac lying freely in the extra-embryonic portion of the body-cavity, appears in the human embryo before the intes-' tine has differentiated from the yolk-sac and pushes its way into the solid mass of mesoderm which forms the belly-stalk (Fig. 66, A). To understand the significance of this process it is neces- sary to recall the abbreviation in the human embryo of the de- velopment of the extra-embryonic mesoderm and body-cavity. Instead of growing out from the embryonic area, as it does in the lower forms, this mesoderm develops in situ from the cellular magma and, furthermore, the extra- embryonic body-cavity arises before there is any trace of a splitting of the embryonic mesoderm (Fig. 39). The belly-stalk, whose development from a portion of the inner cell-mass has already been traced (p. 72), is to be regarded as a portion of the body of "---^/i the embryo, since the ectoderm which ^^^- 67.— Transverse Sec- •^ ' ^ TION THROUGH THE BeLLY- covers one surface of it resembles ex- stalk of an Embryo of 2.1s actly that of the embryonic disk and ^^\ tt v-m- , , „ •^ , -^ Aa, Umbilical (allantoic) shows an extension backward of the artery; ah, allantois; am, am- 1 11 •, r /T7« nion; Va, umbilical (allantoic) medullary groove upon its surface (Fig. ^ein— (His.) 67). The mesoderm, therefore, of the belly-stalk is to he regarded as a portion of the embryonic mesoderm which has not yet undergone a splitting into somatic and splanchnic layers, and, indeed, it never does undergo such a spHtting, so that there is no body-cavity into which the endo- dermal allantoic diverticulum can grow. But this does not account for all the peculiarities of the human allantois. In the birds, and indeed in the lower oviparous mam- mals, the endodermal portion of the allantois is equally developed with the mesodermal portion, the allantois being an extensive sac whose cavity is filled with fluid, and this is also true of such mam- mals as the marsupials, the rabbit, and the ruminants. In man, Il8 THE ALLANIOIS AND BELLY-STALK however, the endodermal diverticulum never becomes a sac-like structure, but is a slender tube extending from the intestine to the chorion and lying in the substance of the mesoderm of the belly- stalk (Fig. 66, D), the greater portion of which is to be regarded as homologous with the relatively thin layer of splanchnic mesoderm covering the endodermal diverticulum of the chick. An explana- tion of this disparity in the development of the mesodermal and endodermal portions of the human allantois is perhaps to be found in the altered conditions under which the respiration and secretion take place. In all forms, the lower as well as the higher, it is the mesoderm which is the more important constituent of the allantois, since in it the blood-vessels, upon whose presence the physiological functions depend, arise and are embedded. In the birds and oviparous mammals there are no means by which excreted material can be passed to the exterior of the ovum, and it is, therefore, stored up within the cavity of the allantois, the allantoic fluid containing considerable quantities of nitrogen, indi- cating the presence of urea. In the higher mammals the intimate relations which develop between the chorion and the uterine walls allow of the passage of excreted fluids into the maternal blood ; ^nd the more intimate these relations, the less necessity there is for an allantoic cavity in which excreted fluid may be stored up. The difference in the development of the cavity in the ruminants, for example, and man depends probably upon the greater intimacy of the union between ovum and uterus in the latter, the arrange- ment for the passage of the excreted material into the maternal blood being so perfect that there is practically no need for the development of an allantoic cavity. The portion of the endodermal diverticulum which is enclosed within the umbilical cord persists until birth in a more or less rudimentary condition, but the intra-embryonic portion extending from the apex of the bladder to the umbilicus becomes converted into a solid cord of fibrous tissue termed the urachus. Occasionally a lumen persists in the urachal portion of the allantois and may open to the exterior at the umbilicus, in which case urine from the bladder may escape at the umbilicus. THE UMBILICAL CORD II 9 • Since the allantois in the human embryo, as well as in the lower.forms, is responsible for respiration and excretion, its blood- vessels are well developed. They are represented in the belly- stalk by two veins and two arteries (Fig. 67), known in human embryology as the umbilical veins and arteries. These extend from the body of the embryo out to the chorion, there branching repeatedly to enter the numerous chorionic villi by which the embryonic tissues are placed in relation with the maternal. The Umbilical Cord. — During the process of closing in of the ventral surface of the embryo a stage is reached in which the embryonic and extra-embryonic portions of the body-cavity are completely separated except for a small area, the umbilicus through which the yolk-stalk passes out (Fig. 66, B) . At the edges of this area in front and at the sides the embryomc ectoderm and somatic mesoderm become continuous with the corresponding layers of the amnion, but posteriorly the line of attachment of the amnion passes up upon the sides of the belly-stalk (Fig. 66, B), so that the whole of the ventral surface of the stalk is entirely un- covered by ectoderm, this layer being limited to its dorsal surface (Fig. 67). In subsequent stages the embryonic ectoderm and somatic mesoderm at the edges of the umbilicus grow out ventrally , carrying with them the line of attachment of the amnion and forming a tube which encloses the proximal part of the yolk- stalk. The ectoderm of the belly-stalk at the same time extend- ing more laterally, the condition represented in Fig. 66, C, is produced, and, these processes continuing, the entire belly-stalk, together with the yolk-stalk, becomes enclosed within a cylindrical cord extending from the ventral surface of the body to the chorion and forming the umbilical cord (Fig. 66, D). From this mode of development it is evident that the cord is, strictly speaking, a portion of the embryo, its surfaces being completely covered by embryonic ectoderm, the amnion being carried during its formation further and further from the umbilicus until finally it is attached around the distal extremity of the cord. In enclosing the yolk-stalk the umbilical cord encloses also a small portion of what was originally the extra-embryonic body I20 THE CHORION al -r uv ua uv Fig. 68. — Transverse Sections of the Umbilical Cord of Embryos of (.4) 1.8 CM. AND {B) 25 CM. al, Allantois; c, ccBlom: ua, umbilical artery; uv, umbilical vein; ys, yolk-stalk. THE CHORION l2I cavity surrounding the yolk-stalk. A section of the cord in an early stage of its development (Fig. 68, A) will show a thick mass of mesoderm occupying its dorsal region; this represents the mesoderm of the belly-stalk and contains the allantois and the umbilical arteries and vein (the two veins originally present in the belly-stalk having fused), while toward the ventral surface there will be seen a distinct cavity in which lies the yolk stalk with its accompanying blood-vessels. The .portion of this coelom nearest the body of the embryo becomes much enlarged, and during the second month of development contains some coils of the small intestine, but later the entire cavity becomes more and more encroached upon by the growth of the mesoderm, and at about the fourth month is entirely obliterated. A section of the cord subsequent to that period of development will show a solid mass of mesoderm in which are embedded the umbilical ar- teries and vein, the allantois, and the rudiments of the yolk- stalk (Fig. 68, B). When fully formed, the umbilical cord measures on the aver- age 55 cm. in length, though it varies considerably in different cases, and has a diameter of about 1.5 cm. It presents the ap- pearance of being spirally twisted, an appearance largely due, however, to the spiral course pursued by the umbilical arteries, though the entire cord may undergo a certain amount of torsion from the movements of the embryo in the later stages of develop- ment and may even be knotted. The greater part of its sub- stance is formed by the mesoderm, the cells of which become stellate and form a reticulum, the meshes of which are occupied by connective-tissue fibrils and a mucous fluid which gives to the tissue a jelly-like consistence, whence it has received the name of Wharton^s jelly. The Chorion. — To understand the developmental changes which the chorion undergoes it wn'U be of advantage to obtain some insight into the manner in which the ovum becomes implanted in the wall of the uterus. Nothing is known as to how this implanta- tion is effected in the case of the human ovum ; it has already been accomplished in the youngest ovum at present known. But the 122 IHE CHORION process has been observed in other mammals, and what takes place in Spermophilus, for example, may be supposed to give a clue to what occurs in the human ovum. In the spermophile the ovum lies free in the uterine cavity up to a stage at which the vacuolization of the central cells is almost completed (Fig. 69, A). At one region of the covering layer the cells become thicker and later form a syncytial projection or knob which comes into Fig. 69. — Successive Stages in the Implantation of the Ovum of THE Spermophile. a. Syncytial knob; k, inner cell-mass. — (Resjek.) contact with the uterine mucosa (Fig. 69, B), and at the point of contact the mucosa cells undergo degeneration, allowing the knob to come into relation with the deeper tissues of the uterus (Fig. 69, C), the process apparently being one in which the mucosa cells are eroded by the syncytial knob. It seems probable that in the human ovum the process is at first of a similar nature and that as the covering layer cells come into contact with the deeper layes of the uterus, these too are eroded, and, the uterine blood-vessels being included in the THE CHORION 123 Umy S ^(1 ^^dL i 1 wM I Pig. 70. — Diagrams Illustrating the Implantation of the Ovum. ac. Amniotic cavity; hs, belly-stalk; cf, chorion frondosum; cl, chorion laeve; dc, decidua capsularis; ic, inner cell-mass; s, space surrounding ovum which becomes the intervillous space; um, uterine mucosa; v, chorionic villus; ys, yolk-sac. 124 THE CHORION erosion process, an extravasation of blood plasma and corpuscles occurs in the vicinity of the burrowing ovum. In the meantime the ovum has increased considerably in size, its growth in these early stages being especially rapid, and the area of contact consequently increases in size, entailing continued erosion of the uterine mucosa. At the same time, too, the uterine tissues surrounding the ovum grow up around it, forming at first as it ScL ^^^r'f^^^- f'»' ..'*.' ^*. •';#.•"' ' S /' .< ' \ <-i.f^^ ^~ -v.' EV. Fig. 71. — Section of an Ovum of i mm. A Section of the Embryo Lies in the Lower Part of the Cavity of the Ovum. D, Decidua; R.U ., uterine epithelium; Sch, blood-clot closing the aperture left by the sinking of the ovum into the uterine mucosa. — {From Strahl, after Peters.) were a circular wall (Fig. 70, A), and eventually completely enclose it, forming an envelope known as the decidua capsularis or reflexa. The blood extravasation is now contained within a closed space bounded on the one hand by the uterine tissues and on the other by the wall of the ovum (Fig. 70, B). The youngest known human ova have already reached ap- proximately this stage. Thus, the Peters ovum (Fig. 71) had already sunk deeply into the uterine mucosa, the point of entrance THE CHORION 12 5 being indicated by a gap in the decidiia capsularis, closed in this case by a patch of coagulated blood (Sch). Ihe uterine tissues in the immediate vicinity of the ovum were much swollen and apparently somewhat necrotic and their blood-vessels could be seen to communicate with the space between the wall of the ovum and the maternal tissues. This space, however, was con- verted into an irregular network of blood lacunae by anastomosing cords of cells, which arose from the wall of the ovum and ex- tended through the space to the maternal tissues; these cords of cells are represented in Fig. 71 by the darker masses projecting from the wall of the ovum and scattered among the paler blood lacunae. This stage of implantation of the ovum is shown dia- grammatically in Fig. 70, B, where, for simplicity's sake, the cell cords are represented merely as processes radiating from the ovum without reaching the maternal tissues. The cell cords are derivatives of the trophoblast and are, there fore, of embryonic origin. If examined under a higher magnifica- tion than that shown in Fig. 70 they will be seen to be composed an axial core of cells with distinct outlines, enclosed within a layer of protoplasm which lacks all traces of cell boundaries, although it contains numerous nuclei, being what is termed a syncytium or Plasmodium. The two tissues represent the two layers differen- tiated from the original trophoblast, the cellular one being the cyto-trophoUast and the plasmodial one the plasmodi-trophohlast. The latter is the tissue that comes into contact with the maternal blood contained in the lacunar spaces and with the maternal tissues, in connection with these latter sometimes developing into masses of considerable extent. To the plasmodi-trophoblast may be ascribed the active part in the destruction of the maternal tissues and probably also the absorption of the products of the destruction for the nutrition of the growing ovum. For up to this stage the ovum has been playing the role of a parasite thriving upon the tissues of its host. The food material that the ovum thus obtains may con- veniently be termed the emhryotroph and the type of placentation which obtains up to this stage and for some time longer may be 126 THE CHORION termed the embryotrophic type. But even in the Peters ovum the preparation for another type has begun. In earlier stages the cell cords were entirely trophoblastic, but in this ovum (Fig. 71) processes from the chorionic mesoderm may be seen projecting into the bases of the cell cords, and in later stages these processes extend farther and farther into the axis of each cord, the anastomoses of the cords disappear and the cords themselves become converted into branching processes, the chorionic villij which project from the entire surface of the ovum (Fig. 72) into the Fig. 72. — Entire Ovum Aborted at about the Beginning of the Second Month. XiM-- — (Grosser.) surrounding space, and are bathed by the maternal blood contained in the surrounding space, which may now be known as the inter- villous space. Toward the maternal surface of the space some masses of the trophoblast still persist, uniting the extremities of certain of the villi to the enclosing uterine wall, such villi being termed fixation villi to distinguish them from others, which project freely into the intervillous space. Later, when the embryonic blood-vessels develop, those associated with the allantois extend outward into the chorionic mesoderm and thence send branches into each villus. The second type of placentation, the hcemotro- THE CHORION 127 phic type, is thus established, the fetal blood contained in the vessels of the villi receiving nutrition through the walls of the villi from the maternal blood contained in the intervillous space, and, similarly, transferring waste products to it. At first, as stated above, the villi usually cover the entire surface of the ovum, but later, as the ovum increases in size, those villi which are remote from the attachment of the belly-stalk to the chorion are placed at a disadvantage so far as their blood supply is concerned and gradually disappear, and this process Fig. 73. — Two Villi from the Chorion of an Embryo of 7 mm. continues until, finally, only those villi are retained which are in the immediate region of the belly-stalk (Fig. 70, C), these per- sisting to form the fetal portion of the placenta. By these changes the chorion becomes differentiated into two regions (Fig. 70, C), one of which is destitute of villi and is termed the chorion Iceve, while the other, provided with them, is known as the chorion frondosum. Occasionally one or more patches of villi may persist in the area that normally becomes the chorion laeve and thus accessory placentce {placentcB succenturiatce) , varying in number and size, may be formed. 128 THE CHORION p.^ ..—Transverse Sections through Chorionic Villi in (A) the Fifth * AND (B) THE Seventh Month of Development. cf Canalized fibrin; Ic, Langhans cells; 5. syncytium .-(A ^hich is more highly •" magnified than B, from Szymonowicz; B from Mtnot.) THE CHORION 129 The villi when fully formed are processes of the chorion, branching profusely and irregularly (Fig. 73), and each consists of~ a core of mesoderm, containing blood-vessels, enclosed within a double layer of trophoblastic tissue (Fig. 74, A). The inner layer consists of a sheet of well-defined cells arranged in a single series; it is derived from the cyto-trophoblast and forms what is known as the layer of Langhans cells. The outer layer is syncytial in structure and is formed from the plasmodi-trophoblast. I Pig. 75. — Mature Placenta after Separation from the uterus. c. Cotyledons; ch, chorion, amnion, and decidua vera; um, umbilical cord. — {Kollmann.) As development proceeds the villi, which are at first distributed evenly over the chorion frondosum, become separated into groups termed cotyledons (Fig. 75) by the growth into the intervillous space of trabeculae from the walls of the uterus, the fixation villi becoming connected with these septa as well as with the general uterine wall. The ectoderm of the villi undergoes also certain changes with advancing growth, the layer of Langhans cells disappearing except in small areas scattered irregularly in the villi, and the syncytium, though persisting, undergoes local thick- enings which become replaced, more or less extensively, by de- positions of fibrin (Fig. 74 B, cj). 130 THE DECIDU^ The changes which occur during the later stages of develop- ment in the chorion are very similar to those described for the villi. Thus, the mesoderm thickens, its outermost layers be- coming exceedingly fibrillar in structure, while later, as in the villi, the syncytial layer of its trophoblast is replaced in irregu- inas rCW^'-^-ftf Fig. 76. — Section through the Placental Chorion of an Embryo of Seven Months. c, Cell layer; ep, remnants of epithelium; fb, fibrin layer; mes, mesoderm. — {Minot.) lar patches by a peculiar form of fibrin which is traversed by flattened anastomosing spaces and to which the name canalized fibrin or fibrinoid has been applied (Fig. 76). The Deciduae. — It has been pointed out (p. 27) that in connec- tion with the phenomenon of menstruation periodic alterations THE DECIDUiE I3I occur in the mucous membrane of the uterus. If during one of these periods a fertilized ovum reaches the uterus, the desquama- tion of portions of the epitheHum does not occur nor is there any appreciable hemorrhage into the cavity of the uterus; the uterine mucosa remains in what is practically the ante-menstrual condi- tion until the conclusion of pregnancy, when, after the birth of the fetus, a considerable portion of its thickness is expelled from Fig. 77. — Diagram showing the relations of the Fetal Membranes. Am, Amnion; Ch, chorion; M, muscular wall of uterus; C, decidua capsularis; B, decidua basalis; V, decidua vera; Y, yolk-stall:. the uterus, forming what is termed the deciduce. In other words, the sloughing of the uterine tissue which concludes the process of menstruation is postponed until the close of pregnancy, and then takes place simultaneously over the whole extent of the uterus. Of course, the changes in the uterine tissues are somewhat more extensive during pregnancy than during menstruation, but there is an undoubted fundamental similarity in the changes during the two processes. 132 THE DECIDU^ The human ovum comes into direct apposition with only a small portion of the uterine wall, and the changes which this portion of the wall undergoes differ somewhat from those occur- ring elsewhere. Consequently it becomes possible to divide the deciduae into (i) a portion which is not in direct contact with the ovum, the decidua vera (Fig. 77, V) and (2) a portion which is. The latter portion is again capable of division. The ovum be- FiG. 78. — Surface view of Half of the Decidua Vera at the End of the Third Week of Gestation. d. Mucous membrane of the Fallopian tubes; ds, prolongation of the vera toward the cervix uteri; pp., papillae; rf, marginal furrow. (Kollmann.) comes completely embedded in the mucosa, but, as has been pointed out, the chorionic villi reach their full development only over that portion of the chorion to which the belly-stalk is at- tached. The decidua which is in relation to this chorion frondo- sum undergoes much more extensive modifications than that in relation to the chorion laeve, and to it the name of decidua basalts {decidua serotina) (Fig. 77, -B) is applied, while the rest of the de- THE DECIDUA VERA 133 cidua which encloses the ovum is termed the decidua capsularis (decidua reflexa) (C) . The changes which give rise to the decidua vera may first be described and those occurring in the others considered in succession. (a) Decidua vera. — On opening a uterus during the fourth or fifth month of pregnancy, when the decidua vera is at the height of its development, the surface of the mucosa » presents a corrugated appearance and is traversed by irregular and rather deep grooves (Fig. 78). This appearance ceases at the internal orifice, the mucous membrane of the cervix uteri not forming a decidua, and the deciduae of the two surfaces of the uterus are separated by a distinct furrow known as the marginal groove. In sections the mucosa is found to have become greatly thickened, frequently meas- uring I cm. in thickness, and its glands have undergone very considerable modifica- tion. Normally almost straight (Fig. 79, A)y they increase in length, not only keeping Fig. 79. — ^DiAGRAMMATic Sections of the Uterine Mucosa, A, in the Non- pregnant Uterus, and B, at the Beginning of Pregnancy. c, Stratum compactum; gl, the deepest portions of the glands; m, muscular layer; sp, stratum spongiosum. — {Kundrat and Englemann.) pace with the thickening of the mucosa, but surpassing its growth, so that they become very much contorted and are, in addition, considerably dilated (Fig. 79, B). Near their mouths they are dilated, but not very much contorted, while lower down the reverse 134 THE DECIDUA CAPSULARIS is the case, and it is possible to recognize three layers in the^de- cidua, (i) a stratum compactum nearest the lumen of the uterus, containing the straight but dilated portions of the glands; (2) a stratum spongiosum, so called from the appearance which it presents in sections owing to the dilated and contorted portions of the glands being cut in various planes; and (3) next the mus- ciflar coat of the uterus a layer containing the contorted but not dilated extremities of the glands is found. Only in the last layer does the epithelium of the glands retain its normal columnar form ; elsewhere the cells, separated from the walls of the glands, become enlarged and irregular in shape and eventually degenerate. In addition to these changes, the epithelium of the mucosa disappears completely during the first month of pregnancy, and the tissue between the glands in the stratum compactum becomes packed with large, often multinucleated cells, which are termed the decidual cells and are probably derived from the connective tissue cells of the mucosa. After the end of the fifth month the increasing size of the embryo and its membranes exerts a certain amount of pressure on the decidua, and it begins to diminish in thickness. The portions of the glands which lie in the stratum compactum become more and more compressed and finally disappear, while in the spongi- osum the spaces become much flattened and the vascularity of the whole decidua, at first so pronounced, diminishes greatly. {h) Decidua capsularis. — The decidua capsularis has also been termed the decidua reflexa, on the supposition that it was formed as a fold of the uterine mucosa reflected over the ovum after this had attached itself to the uterine wall. Since, however, the attachment of the ovum is to be regarded as a process of burrowing into the uterine tissues (see p. 122), the necessity for an upgrowth of a fold is limited to an elevation of the uterine tissues in the neighborhood of the ovum to keep pace with its increasing size. Since it is part of the area of contact with the ovum it possesses no epithelium upon the surface turned toward the ovum, although in the earlier stages its outer surface is covered by an epithehum continuous with that of the decidua vera , and between it and the THE DECIDUA BASALIS I35 chorion there is a portion of the blood extravasation in which the villi formed from the chorion laeve float. Glands and blood-vessels also occur in its walls in the earlier stages of development. As the ovum continues to increase in size the capsularis begins to show signs of degeneration, these appearing first over the pole of the ovum opposite the point of fixation. Here, even in the case of the ovum described by Rossi Doria, the cavity of which measured 6X5 mm. in diameter, it has become reduced to a thin membrane destitute of either blood-vessels or glands, and the degeneration gradually extends throughout the entire capsule, the portion of the blood space which it encloses also disappearing. At about the fifth month the growth of the ovum has brought the capsularis in contact throughout its whole extent with the vera, and it then appears as a whitish transparent membrane with no trace of either glands or blood-vessels, and it eventually disappears by fusing with the vera. (c) Decidua hasalis. — The structure of the decidua basalis, also known as the decidua serotina, is practically the same as that of the vera up to about the fifth month. It differs only in that, being part of the area of contact of the ovum, it loses its epithelium much earlier and is also the seat of extensive blood extravasations, due to the erosion. of its vessels by the chorionic trophoblast. Its glands, however, undergo the same changes as those of the vera, so that in it also a compactum and a spongiosum may be recog- nized. Beyond the fifth month, however, there is a great differ- ence between it and the vera, in that, being concerned with the nutrition of the embryo, it does not partake of the degeneration noticeable in the other deciduae, but persists until birth, forming a part of the structure termed the placenta. The Placenta. — This organ, which forms the connection be- tween the embryo and the maternal tissues, is composed of two parts, separated by the intervillous space. One of these parts is of embryonic origin, being the chorion frondosum, while the other belongs to the maternal tissues and is the decidua basalis. Hence the terms placenta fetalis and placenta uterina frequently applied to the two parts. The fully formed placenta is a more 136 ' THE PLACENIA or less discoidal structure, convex on the surface next the uterine muscularis and concave on that turned toward the embryo, the umbilical cord being continuous with it near the center of the latter surface. It averages about 3.5 cm. in thickness, thinning out somewhat toward the edges, and has a diameter of 15 to 20 cm., and a weight varying between 500 and 1250 grams. It is situated on one of the surfaces of the uterus, the posterior more frequently than the anterior, and usually much nearer the fundus than the internal orifice. It develops, in fact, wherever the ovum happens to become attached to the uterine walls, and occasionally this attachment is not accomplished until the ovum has descended nearly to the internal orifice, in which case the placenta may com- pletely close this opening and form what is termed a placenta prcBvia. If a section of a placenta in a somewhat advanced stage of de- velopment be made, the following structures may be distinguished : On the inner surface there will be a delicate layer representing the amnion (Fig. 80, Am), and next to this a somewhat thicker one which is the chorion (Cho) , in which the degenerative changes al- ready mentioned may be observed. Succeeding this comes a much broader area composed of the large intervillous blood space in which lie sections of the villi (vi) cut in various directions. Then follows the stratum compactum of the basalis, next the stratum spongiosum (D^), next the outermost layer of the mucosa (Z>")> ill which the uterine glands retain their epithelium, and, finally the muscularis uteri (Mc). These various structures have, for the most part, been already described and it remains here only to say a few words concerning the special structure of the basal compactum and concerning certain changes that take place in the intervillous space. The stratum compactum of the basal decidua forms what is termed the basal plate of the placenta, closing the intervillous space on the uterine side and being traversed by the maternal blood- vessels that open into the space. The formation of canalized fibrin, already mentio^ied in connection with the decidua vera and the syncytium of the villi, also occurs in the basal portion of the THE PLACENTA 137 Fig. 80. — Section through a Placenta of Seven Months' Development. Am, Amnion; cho, chorion; D, layer of decidua containing the uterine glands; Mc, muscular coat of the uterus; Ve, maternal blood-vessel; Vi, stalk of a villus; vi, villi in section.^ — (Minoi.) 138 THE PLACENTA 2J t3 . to •-< O. S O M-. S 2S ^ ^§ w ^'^ < B . o ? S >| M u A )^ a « S2 5 o a. -5^ r d o rt 2- SEPARATION OF THE DECIDU^ I39 decidua, a definite layer of it, known as Nitabuch^s fibrin stria, being a characteristic constituent of the basal plate and patches of greater or less extent also occur upon the surface of the plate. Leucocytes also occur in considerable abundance in the plate and their presence has been taken to indicate an attempt on the part of the maternal tissues to resist the erosive action of the parasitic ovum. From the surface of the basal plate processes, termed placental septa, project into the intervillous space, group- ing the villi into cotyledons and giving attachment to some of the fixation villi (Fig. 81). Throughout the greater extent of the placenta the septa do not reach the surface of the chorion, but at the periphery, throughout a narrow zone, they do come into contact with the chorion and unite beneath it to form a membrane which has been termed the closing plate. Beneath this lies the peripheral portion of the intervillous space, which, ow'ng to the arrangement of the septa in this region, appears to be imperfectly separated from the rest of the space and forms what is termed the marginal sinus (Fig. 81). Attention has already been called to the formation of canalized fibrin or fibrinoid in connection with the syncytium of the villi. In the later stages of pregnancy there may be produced by this process masses of fibrinoid of considerable size, lying in the inter- villous space; these, on account of their color, are termed white infarcts and may frequently be observed as whitish or grayish patches through the walls of the placenta after its expulsion. Red infarcts produceid by the clotting of the blood, also occur, but with much less regularity and frequency. The Separation of the Deciduae at Birth.— At parturition, after the rupture of the amnion and the expulsion of the fetus, there still remain in the uterine cavity the deciduse and the amnion, which is in contact but not fused with the deciduae. A continu- ance of the uterine contractions, producing what are termed the "after-pains," results in the separation of the placenta from the uterine walls, the separation taking place in the deep layers of the spongiosum, so that the portion of the mucosum which contains the undegenerated glands remains behind. As soon as the I40 SEPARATION OF THE DECIDU^ placenta has separated, the separation of the decidua vera takes place gradually though rapidly, the Hne of separation again being in the deeper layers of the stratum spongiosum, and the whole of the deciduae, together with the amnion, is expelled from the uterus forming what is known as the '' after-birth." • Hemorrhage from the uterine vessels during and after the separation of the deciduae is prevented by the contractions of the uterine walls, assisted, according to some authors, by a pre- liminary blocking of the mouths of the uterine vessels by certain large polynuclear decidual cells found during the later months of pregnancy in the outer layers of the decidua basalis. The re- generation of the uterine mucosa after parturition has its start- ing-point from the epithehum of the undegenerated glands which persist, this epithelium rapidly evolving a complete mucosa over the entire surface of the uterus. The complicated arrangement of the human placenta is, of course, the culmination of a long series of specializations, the path along which these have proceeded being probably indicated by the conditions ob- taining in some of the lower mammals. The Monotremes resemble the reptiles in being oviparous and in this group of forms there is no relation of the ovum to the maternal tissues such as occurs in the formation of a placenta. In the other mammals viviparity is the rule and this condition does demand some sort of connection between the fetal and maternal tissues. One of the simplest of such con- nections is that seen in the pig, where the chorionic villi of the ovum fit into corresponding depressions in the uterine mucosa, this tissue, however, undergoing no destruction, and at birth the villi simply withdraw from the depressions of the mucosa, leaving it intact. This type of placentation is an embryotrophic one, and since there is no separation of deciduae from the uterine wall after pregnancy it is also of the indeciduate type. In the sheep the placentation is also embryo- trophic and indeciduate, but destruction of the maternal mucosa does take place, the villi penetrating deeply into it and coming into rela- tion with the connective tissue surrounding the maternal blood-vessels. Another step in advance is shown by the dog, in which even the connective tissue around the maternal vessels in the placental area undergoes almost complete destruction so that the chorionic villi are separated from the maternal blood practically only by the endothelial lining of the maternal vessels. In this case the mucosa undergoes so much alteration that the undestroyed portions of it are sloughed off after birth as a decidua, so that the placentation, like that in man, is t LITERATURE I41 of the deciduate type. It still represents, however, an embryotrophic type, although closely approximating to the haemotrophic one found in man, in which, as described above, the destruction of the maternal tissues proceeds so far as to open into the maternal blood-vessels, so that the fetal villi are in direct contact with the maternal blood. If these various stages may be taken to represent steps by which the conditions obtaining in the human placenta have been evolved, the entire process may be regarded as the result of a progressive activity of a parasitic ovum. In the simplest stage the pabulum supplied by the uterus was sufficient for the nutrition of the parasite, but gradu- ally the ovum, by means of its plasmodi-trophoblast, began to attack the tissues of its host, thus obtaining increased nutrition, until finally, breaking through into the maternal blood-vessels, it achieved for itself still more favorable nutrition, by coming into direct contact with the maternal blood. LITERATURE In addition to the papers by Beneke and Strahl, Bryce and Teacher, Frassi, Jung, Herzog, Grosser and Linzenmeier cited in Chapter III, the following may be mentioned: A. Branca: "Recherches sur la structure, revolution et le r61e de la vesicule om- bilicale de I'homme" Joiirn. de VAnat. el de la Physiol., xldc, 1913. E.Cova: "Ueber ein menschliches Ei der zweiten Woohe:,'' Arch, fur Gynaek., lxxxiii, 1907. A. Debeyre: "Description d'un embryon humain de 0.9 mm.," Journ. de VAnat. et de la Physiol, xlviii, i 9 i 2 . L. Frassi: "Ueber ein junges menschliches Ei in situ," Arch. fUr mikr. Anat., lxx, 1907. O. Grosser: " Vergleichende Anatomie und Entwicklungsgeschichte der Eihaute und der Placenta mit besonderer Beriicksichtigung des Menschen," Wien, 1909. H. Happe: " Beobachtungen an Eihauten junger menschlicher Eier," Anat. Hefte, xxxii, 1906. W. His: "Die Umschliessung der menschlichen Frucht wahrend der fruhesten Zeit des Schwangerschafts," Archiv fiir Anat. und Physiol., Anat. Abth., 1897. M. Hofmeier: "Die menschliche Placenta," Wiesbaden, 1890. R. W. Johnstone: "Contribution to the study of the early human ovum," Journ. Ohstet. and Gynaek., xxvi, 1914. F. Keibel: "Zur Entwickelungsgeschichte der Placenta," Anat. Anzeiger, iv, 1889. F, Keibel: "Ueber die Grenze zwischen miitterlichen und fetalen Gewebe," Anat. Anzeiger, xlviii, 191 5. J. Kollmann: "Die menschlichen Eier von 6 mm. Grosse," Archiv fur Anat. und Physiol., Anat. Abth., 1879. T. G. Lee: "Implantation of the ovum in Spermophilus tridecemlineatus Mitch." MarklAnniversary Volume, New York, 1904. G. Leopold: "Ueber ein sehr junges menschliches Ei in situ," Arb. aus der konigl. Frauenklinik in Dresden, w, 1906. 142 \. LITERATURE. F. Marchand: "^Btobaehtungen an jungen menschlichen Eiern," Anat. Hefte, xxi, 1903. J. Merttens: "Beitrage zur normalen und pathologischen Anatomic der mensch- lichen Placenta," Zeitschriftfiir Geburtshulfe und Gynaekol., xxx and xxxi, 1894. C. S. Minot: "Uterus and Embryo," Journal of Morphol., 11, 1889. G. Paladino: "Sur la genese des espaces intervilleux du placenta humain et de leur premier contenu, comparativement d la meme partie chez quelques mammiferes, Archives Ital. de Biolog., xxxi and xxxii, 1899. H. Peters: "Ueber die Einbettung des menschlichen Eies und das friiheste bisher bekannte menschliche Placentationsstadium," Leipzig und Wien, 1899. J. Rejsek: "Anheftung (Implantation) des Saiigetiereies an die Uteruswand, insbe- sondere des Eies von Spermophilus citellus/Mrc/f./wr mikrosk. Anat., lxiii, 1904. T. Rossi Doria: "Ueber die Einbettung des menschlichen Eies, studirt an einem kleinen Eie der zweiten Woche," Arch, fiir Gynaek., lxxvi, 1905. C. Ruge: "Ueber die menschliche Placentation," Zeitschrijt fiir Geburtshulfe und Gynaekol, xxxix, 1898. Siegenbeek VAN Heukelom: "Ueber die menschliche Placentation," Arch. f. Anat. und Phys., Anat. Abth., 1898. F. Graf Spee: "Ueber die menschliche Eikammer und Decidua reflexa," Verhandl. des Anat. Gesellsch., xii, 1898. H. Strahl: "Die menschliche Placenta," Ergebn. der Anat. und Entwickl., ii, 1893. "Neues iiber den Bau der Placenta," ibid, vi, 1897. "Placentaranatomie," ibid. ,vin, 1899. R. ToDYO: "Ein junges menschliches Ei," Arch. fUr Gynaek., xcv, 1912. Van Cauwenberghe: "Recherches sur la role du Syncytium dans la nutrition embryonnaire de la femme," Arch, de Biol., xxiii, 1907. J. C. Webster: "Human Placentation," Chicago, 1901. E. Wormser: "Die Regeneration der Uterusschleimhaut nach der Geburt," Arch. fiir Gynaek., Lxrx, 1903. PART II ORGANOGENY CHAPTER VI THE DEVELOPMENT OF THE INTEGUMENTARY SYSTEM The Development of the Skin. — The skin is composed of two embryologically distinct portions, the outer epidermal layer being developed from the ectoderm, while the dermal layer is mesen- chymatous in its origin. The ectoderm covering the general surface of the body is, in the earliest stages of development, a single layer of cells, but at the end of the first month it is composed of two layers, an outer one, the epitrichium, consisting of slightly flattened cells, and a lower one whose cells are larger, and which will give rise to the epidermis (Fig. 82, A). During the second month the differences between the two layers become more pronounced, the epitrichial cells assuming a characteristic domed form and becoming vesicular in structure (Fig. 82, B). These cells persist until about the sixth month of development, but after that they are cast off, and, becoming mixed with the secretion of sebaceous glands which have appeared by this time, form a constituent of the vernix caseosa. In the meantime changes have been taking place in the epi- dermal layer which result in its becoming several layers thick (Fig. 82, B), the innermost layer being composed of cells rich in protoplasm, while those of the outer layers are irregular in shape and have clearer contents. As development proceeds the number of layers increases and the superficial ones, undergoing a horny degeneration, give rise to the stratum corneum, while the deeper 143 144 DEVELOPMENT OF THE SKIN ones become the stratum Malpighii. At about the fourth month ridges develop on the under surface of the epidermis, projecting downward into the dermis, and later secondary ridges appear in the intervals between the primary ones, while on the palms and soles ridges appear upon the outer surface of the epidermis, corre- sponding in position to the primary ridges of the under surface. The mesenchyme which gives rise to the dermis grows in from all sides between the epidermis and the outer layer of the myo- tomes, which are at first in contact, and forms a continuous layer Fig. 82. — A, Section of Skin from the Dorsum of Finger of an Embryo of 4.5 CM, B, from the Plantar Surface of the Foot of an Embryo of 10.2 cm. et, Epitrichium; ep, epidermis. underlying the epidermis and showing no indications of a seg- mental arrangement. It becomes converted principally into fibrous connective tissue, the outer layers of which are relatively compact, while the deeper ones are looser, forming the subcu- taneous areolar tissue. Some of the mesenchymal cells, how- ever, become converted into non-striated muscle-fibers, which for the most part are few in number and associated with the hair follicles, though in certain regions, such as the skin of the scrotum, they are very numerous and form a distinct layer known as the dartos. Some cells also arrange themselves in groups and undergo DEVELOPMENT OF THE NAILS 145 a fatty degeneration, well-defined masses of adipose tissue embedded in the lower layers of the dermis being thus formed at about the sixth month. Although the dermal mesenchyme is unseg- mental in character, yet the nerves which send branches to it are ■ segmental, and it might be expected that indications of this condition would be retained by the cutaneous nerves even in the adult. A study of the cutaneous nerve-supply in the adult realizes to a very considerable extent this expectation, the areas supplied by the vari- ous nerves forming more or less distinct zones, and being therefore segmental (Fig. 83). But a considerable commingling of adjacent areas has also occurred. Thus, while the distribution of the cutaneous branches of the fourth thoracic nerve, as determined experimentally in the monkey (Macacus), is distinctly zonal or segmental, the nipple lying practically in the middle line of the zone, the upper half of its area is also supplied or overlapped by fibers of the third nerve and the lower half by fibers of the fifth (Fig. 84), so that any area of skin in the zone is innervated by fibers coming from at least two segmental nerves (Sherrington). And, furthermore, the distribu- tion of each nerve crosses the mid-ventral line of the body, forming a more or less extensive crossed overlap. And not only is there a confusion of adjacent areas but an area may shift its position relatively to the deeper structures supplied by the same nerve, so that the skin over a certain muscle is not necessarily supplied by fibers from the nerve which supplied the muscle. Thus, in the lower half of the abdomen, the skin at any point will be supplied by fibers from higher nerves than those supplying the underlying muscles (Sherrington), and the skin of the limbs may receive twigs from nerves which are not represented at all in the muscle-supply (second and third thoracic and third sacral). The Development of the Nails. — The earliest indications of the development of ^ the 10 7> rj\ rs Te T9 Fro ^Tn Sz Lt U Sf Fig. 83. — Diagram showing the cuta- NEOUS Distribution OF THE Spinal Nerves. —{Head.) 146 DEVELOPMENT OF THE NATLS nails have been described by Zander in embryos of about nine weeks as slight thickenings of the epidermis of the tips of the digits, these thickenings being separated from the neigh- boring tissue by a faint groove. Later the nail areas migrate i VWhi \\\m\\mm\\mw Fig. 84. — Diagram showing the Overlap of the ///, IV, and V Intercostal Nerves of a Monkey. — {Sherrington.) .nf ^ttcl^l^^^^fe-^O-^^&.^r-^^^ Pig. 85. — Longitudinal Section through the Terminal Joint of the Index- finger OF AN Embryo of 4.5 cm. e. Epidermis; ep, epitrichium; «/, nail fold; Ph, terminal phalanx; sp, sole plate. to the dorsal surfaces of the terminal phalanges (Fig. 85) and the grooves surrounding the areas deepen, especially at their proximaLedges, where they form the nail-folds (nf), while distally thickenings of the epidermis occur to form what have been termed DEVELOPMENT OF THE NAILS 147 sp- sc ep sole-plates {sp), structures quite rudimentary in man, but largely developed in the lower animals, in which they form a considerable portion of the claws. The actual nail substance does not form, however, until the embryo has reached a length of about 17 cm. By this time the epidermis has become several layers thick and its outer m^Jlb layers, over the nail areas as well s elsewhere, have become transformed into ^he stratum corneum (Fig. 86, sc), and it is in the deep layers of this (the stratum lucidum) that keratin granules develop in cells which degenerate to give rise to the nail substance {n) . At its first formation, accordingly the nail is covered by the outer layers of the stratum corneum as well as by the epitrichium, the two together forming what has been termed the eponychium (Fig.; 86, ep). The epitrichium soon disappears, how-^ ever, leaving only the outer layers of the stratum corneum as a covering, and this also later dis- appears with the exception of a narrow band surrounding the base of the nail which persists as the perionyx. The formation of the nail begins in the more proximal portion of the nail area and its further growth is by the addition of new keratinized cells to its proximal edge and lower surface, these cells being formed only in the proximal part of the nail bed in a region marked by its whitish color and termed the lunula. The first appearance of the nail areas at the tips of the digits as described by Zander has not yet been confirmed by later observers, but the migra- tion of the areas to the dorsal surfaces necessitated by such a location of the primary differentiation affords an explanation of the otherwise anomalous cutaneous nerve-supply of the nail areas in the adult, this being from the palmar (plantar) nerves. Fig. 86. — ^Longi- tudinal Section THROUGH THE NaIL Area in an Embryo OF 17 CM. ep, Eponychium; n, nail substance; nb, nail bed; sc, stratum corneum; sp, sole plate. — (jOkamura.) 148 DEVELOPMENT OF THE HAIRS The Development of the Hairs. — The hairs begin to develop at about the third month and continue to be formed during the remaining portions of fetal life. They arise as solid cylindrical downgrowths, projecting obliquely into the subjacent dermis from the lower surface of the epidermis. As these downgrowths con- tinue to elongate, they assume a somewhat club-shaped form (Fig. 87, A), and later the extremity of each club moulds itself m. L hj Fig. 87. — The Development of a Hair. c. Cylindrical cells of stratum mucosum; hj, wall of hair follicle; w, mesoderm; mu, stratum mucosum of epidermis; p, hair papilla; r, root of hair; 5, sebaceous gland. — (Kollmann.) over the summit of a small papilla which develops from the dermis (Fig. 87, -S). Even before the dermal papilla has made its appearance, however, a differentiation of the cells of the down- growth becomes evident, the central cells becoming at first spindle- shaped and then undergoing a keratinization to form the hair shaft, while the more peripheral ones assume a cuboidal form and DEVELOPMENT OF THE HAIRS 1 49 constitute the lining of the hair follicle. The further growth of the hair takes place by the addition to its basal portion of new keratinized cells, probably produced by the multiplication of the epidermal cells which envelop the papilla. From the cells which form the lining of each follicle an out- growth takes place into the surrounding dermis to form a se- baceous gland, which is at first solid and club-shaped, though later it becomes lobed. The central cells of the outgrowth separate from the peripheral and from one another, and, their protoplasm undergoing a fatty degeneration, they finally pass out into the space between the follicle walls and the hair and so reach the surface, the peripheral cells later giving rise by division to new generations of central cells. During fetal life the fatty material thus poured out upon the surface of the body becomes mingled with the cast-off epitrichial cells and constitutes the white oleaginous substance, the vernix caseosa, which covers the surface of the new-born child. The muscles, arrectores pilorum, connected with the hair follicles arise from the mesenchyme cells of the surrounding dermis. The first growth of hair forms a dense covering over the entire surface of the fetus, the hairs which compose it being exceedingly fine and silky and constituting what is termed the lanugo. This growth is cast off soon after birth, except over the face, where it is hardly noticeable on account of its extreme fineness and lack of coloration. The coarser hairs which replace it in certain regions of the body probably arise from new follicles, since the formation of follicles takes place throughout the later periods of fetal life and possibly after birth. But even these later formed hairs do not individually persist for any great length of time, but are con- tinually being shed, new or secondary hairs normally developing in their places. The shedding of a hair is preceded by a cessation of the proliferation of the cells covering the dermal papilla and by a shrinkage of the papilla, whereby it becomes detached from the hair, and the replacing hair arises from a papilla which is prob- ably budded off from the older one before its degeneration and carries with it a cap of epidermal cells. ISO DEVELOPMENT OF THE SUDORIPAROUS GLANDS It is uncertain whether the cases of excessive development of hair over the face and upper part of the body which occasi onally occur are due to an excessive development of the later hair follicles (hyper- trichosis) or to a persistence and continued growth of the lanugo. The Development of the Sudoriparous Glands. — The sudori- parous glands arise during the fifth month as solid cylindrical outgrowths from the primary ridges of the epidermis (Fig. 88), and at first project vertically downward into the subjacent dermis. Later, however, the lower end of each downgrowth is thrown into coils, and at the same time a lumen appears in the center. Since, however, the cylinders are formed from the deeper layers of the epidermis, their lumina do not at first open upon the surface, 1 M 1 '^VT^'^u L^^^ ^ ^^^ gradually approach it as the 't^--S I'li^^ ^^^^^ ^^ ^^^ deeper layers of the '( U/TJ, LMiyn^XHM£V / V epidermis replace those which are continually being cast off from the surface of the stratum corneum. The final opening to the surface occurs during the seventh month of development. The Development of the Mammary Glands. — In the ma- jority of the lower mammals a number of mammary glands occur, arranged in two longitudinal rows, and it has been observed that in the pig the first indication of their development is seen in a thickening of the epidermis along a line situated at the junction of the abdominal walls with the membrana reuniens (Schulze). This thickening subsequently becomes a pronounced ridge, the milk ridge, from which, at certain points, the mammary glands develop, the ridge disappearing in the intervals. In human embryos 8 mm. or less in length a similar epidermal thickening has been observed extending from just below the axilla to the inguinal region (Fig. 89). Later, in embryos of 10 to 13 mm., the anterior part of the thickening becomes more distinct while its lower two-thirds become less distinct and eventually disappear. Fig. 88. — ^Lower Surface of a De- tached Portion of Epidermis from THE Dorsum of the Hand. h, Hair follicle: s, sudoriparous gland, —{Blaschko.) DEVELOPMENT OF THE MAMMARY GLANDS 151 In somewhat older embryos (14 to 18 mm.) the gland is rep- resented by a marked thickening of the epidermis which projects down into the dermis and has a circular outline (Fig. 90, A). Later the thickening becomes lobed (Fig. 90, B), and its superficial and central cells become cornified and are cast off, so that the gland area appears as a depression of the surface of the skin. During the fifth and sixth months the lobes elongate into solid cylindrical columns of cells (Fig. 91) resembling not a little the cylinders which become con- verted into sudoriparous glands, and each column becomes slightly enlarged at its lower end, from wh ich outgrowths be- gin to develop to form the acini. A lumen first appears in the lower ends of the col- umns and is formed by the separation and breaking down of the central cells, the peri- pheral cells persisting as the lining of the acini and ducts. The elevation of the gland Fig. 89. — Milk Ridge (mr) in a Human 1 ,1 r , r Embryo. — (Kallius.) area above the surface to form the nipple appears to occur at different periods in different embryos and frequently does not take place until after birth. In the re- gion around the nipple sudoriparous and sebaceous glands develop, the latter also occurring within the nipple area and fre- quently opening into the extremities of the lacteal ducts. In the areola, as the area surrounding the nipple is termed, other glands known as Montgomery's glands, also appear, their development resembling that of the mammary gland so closely as to render it probable that they are really rudimentary mammary glands, perhaps developments of portions of the original milk ridge other than that which gives rise to the main gland. The further development of the glands, consisting of an in- crease in the length of the ducts and the development from them of 152 DEVELOPMENT OF THE MAMMARY GLANDS additional acini, continues slowly up to the time of puberty in both sexes, but at that period further growth usually ceases in the male, while in females it continues for a time and the subjacent dermal tissues, especially the adipose tissue, undergo a rapid development. The occurrence of a milk ridge in human embryos is of special inter- est in connection with the occasional formation of supernumerary '^^^^--^■' -■ ■.:. ^ Fig. 90. — Sections through the Epidermal Thickenings which Represent THE Mammary Gland in Embryos (A) of 6 cm. and (B) of 10.2 cm. mammary glands (polymastia). This is by no means an infrequent anomaly; it has been observed in 19 per cent, of over 100,000 soldiers of the German army and in 47 per cent, of the individuals of certain regions of Germany. The anomalous glands may appear anywhere along the line of the original milk ridge, though they are occasionally found elsewhere, as, for instance, on the inner surface of the thigh. They also vary greatly in their development, their presence being fre- quently indicated merely by a nipple-like elevation (hypertheHa). Such accessory nipples sometimes occur in the areolar area of an other- wise normal gland and in such cases may represent an hypertrophy of one or more of Montgomery's glands. LITERATURE 1 53 It is stated that a slight and temporary enlargement of the gland occurs at each premenstrual period, but if pregnancy supervenes marked enlargement occurs and a certain amount of secretion is formed, this, however, not being true milk, but a watery fluid, rich in proteids and known as colostrum. It is only after parturition that the secre- tion of milk begins, apparently standing in some relation to the expul- sion of the fetus. It was formerly supposed that the correlation of the activity of the mammary glands with uterine conditions was dependent upon some nervous connection, but this has been shown to be fallacious and it seems more probable that the stimulus which excites the gland is chemical in its nature. There is experimental evidence that indicates Fig. 91. — Section through the Mammary Gland of an Embryo of 25 cm. I, Stroma of the gland. — (From Nagel, after Basch.) that the growth of the gland during pregnancy is due to a hormone produced in the tissues of the embryo and fetus, this hormone inhibiting milk secretion, while it stimulates the growth of the gland, and on the explusion of the fetus, the cause or the inhibition being removed, the hypertrophied gland starts to function. Although the glands are nor- mally functional only in females, cases are not unknown in which they have become well developed and functional in males {gynoecomastia) . Furthermore, a functional activity of the glands normally occurs im- mediately after birth, infants of both sexes yielding a few drops of a milky fluid, the so-called witch-milk (Hexenmilch), when the glands are subjected to pressure. LITERATURE R. Bonnet: "Die Mammarorgane im Lichte der Ontogenie und Phylogenie," Ergebn. Anat. und Entwick., 11, 1892; vii, 1898. J. T. Bowen: "The Epitrichial Layer of the Human Epidermis," Anat. Anzeiger, TV, 1889. Brouha: "Recherches sur les diverses phases du d^veloppement et de I'activite de la mammelle," Arch, de Biol., xxi, 1905. G. Burckhard: "Ueber embryonale Hypermastie und H3^erthelie," Anat. Hefte, • VIII, 1897. 1 54 LITERATURE H. Eggeling: "Ueber ein wichtiges Stadium in der Entwicklumgsgeschichte der menschlichen Brustdriise," AnaL Anzeiger, xxiv, 1896. H. Head: "On Disturbances of SensE^tion with Special Reference to the Pain of Visceral Disease," Brain, xvi, i892;xvii, 1894; andxrx, 1896. E. Kallius: "Ein Fall von Milchleiste bei einem menschlichen Embryo," Anal. Hefte, vni, 1897. J. E. Lane-Claypon and E. S. Starling: "An Experimental inquiry into the factors which determine the growth and activity of the mammary glands," Proc. Roy. Soc. London, Ser. B.y lxxvii, 1906. Hilda Lustig: "Zur Entwicklungsgeschichte der menschlichen Bnistdriise." Arch, fur mikr. AnaL, lxxxvii, 1915. T. Okamura: "Ueber die Entwicklung des Nagels beim Menschen," Archiv fur Dermatol, und SyphiloL, xxv, 1900. H. Schmidt: "Ueber normale Hyperthelie menschlicher Embryonen und iiber die erste Anlage der menschlichen Milchdriisen uberhaupt," Morphol. Arheiten, xvii, 1897. O. Schultz: "Ueber die erste Anlage des milchdriisen Apparates." Anat. An- zeiger, viii, 1892. C. S. Sherrington: "Experiments in Examination of the Peripheral Distribution of the Fibres of the Posterior Roots of some Spinal Nerves," Philos. Trans. Royal, Soc, CLXxxiv, 1893, and cxc, 1898. P. Stohr: " Entwickelungsgeschichte des menschlichen Wollhaares," Anat. Hefte. xxiii, 1903. M. Strahl: "Die erste Entwicklung der Mammarorgane beim Menschen," Verhandl. Anat. Gesellsch., xii, 1898. R. Zander: "Die fruhesten Stadien der Nagelentwicklung und ihre Beziehungen zu den Digitalnerven, Arch, fur Anat. und Physiol., Anat. Ahth., 1884. CHAPTER VII THE DEVELOPMENT OF THE CONNECTIVE TISSUES AND SKELETON It has been seen that the cells of a very considerable portion of the somatic and splanchnic mesoderm, as well as of parts of the mesodermic somites, become converted into mesenchyme. A very considerable portion of this becomes converted into what are termed connective or supporting tissues, characterized by con- sisting of a non-cellular matrix in which more or less scattered cells are embedded. These tissues enter to a greater or less extent into the formation of all the organs of the body, with the exception of those forming the central nervous system, and constitute a network, which holds together and supports the elements of which the organs are composed; in addition, they take the form of definite membranes (serous membranes, fasciae), cords (tendons, ligaments), or solid masses (cartilage), or form looser masses or layers of a somewhat spongy texture (areolar tissue). The inter- mediate substance is somewhat varied in character, being com- posed sometimes of white, non-branching, non-elastic fibers; some- times of yellow, branching, elastic fibers; of white, branching, but inelastic fibers which form a reticulum; or of a soft gelatinous substance containing considerable quantities of mucin, as in the tissue which constitutes the Whartonian jelly of the umbilical cord. Again, in cartilage the matrix is compact and homo- geneous, or, in other cases, more or less fibrous, passing over into ordinary fibrous tissue, and, finally, in bone the organic matrix is largely impregnated with salts of lime. Two views exist as to the mode of formation of the matrix, some authors maintaining that in the fibrous tissues it is produced by the actual transformation of the mesenchyme cells into fibers, while others claim that it is manufactured by the cells but does not 155 156 DEVELOPMENT OF CONNECTIVE TISSUE directly represent the cells themselves. Fibrils and material out of which fibrils could be formed have undoubtedly been observed in connective-tissue cells, but whether or not these are later passed to the exterior of the cell to form a connective-tissue fiber is not yet certain, and on this hangs mainly the difference between the theories. >^ Recently it has been held (Mall) that the mesenchyme of the embryo is really a syncytium in and from the protoplasm^of which a^^^^l^ (ir^('o i^' W^ m r, ^ Fig. 92. — Portion of the Center of Ossification of the Parietal Bone of a Human Embryo. the matrix forms; if this be correct, the distinction which the older views make between the intercellular and intracellular origin of the matrix becomes of little importance. Bone differs from the other varieties of connective tissue in that it is never a primary formation, but is always developed either in fibrous tissue or cartilage; and according as it is associated with the one or the other, it is spoken of as membrane bone or cartilage bone. In the development of membrane bone some of the con- nective-tissue cells, which in consequence become known as osteo- blasts, deposit lime salts in the matrix in the form of bony spicules which increase in size and soon unite to form a network (Fig. 92). The trabeculae of the network continue to thicken, while, at the same time, the formation of spicules extends further out into the connective-tissue membrane, radiating in all directions from the region in which it first developed. Later the connective DEVELOPMENT OF BONE 157 tissue which h*es upon either surface of the reticular plate of bone thus produced condenses to form a stout membrane, th^- periosteum, between which and the osseous plate osteoclasts arrange themselves in a more or less definite layer and deposit upon the surface of the plate a lamella of compact bone. A membrane bone, such as one of the flat bones of the skull, thus comes to be composed of two plates of compact bone, the inner and outer tables, enclosing and united to a middle plate of spongy bone which constitutes the diploe. With bones formed from car- tilage the process is somewhat different. In the center of the cartilage the intercellular matrix becomes increased so that the cells appear to be more scattered and a calcareous deposit forms in it. All around this region of calcification the cells arrange themselves in rows (Fig. 93) and the process of calcification ex- tends into the trabeculae of mat- rix which separate these rows. While these processes have been ^^ 3^^ months. * c. Cartilage trabeculas; p, periosteal takmg place the mesenchyme bone; po, periosteum; x, ossification surrounding the cartilage has be- eenter.-(5.ymono^/...) come converted into a periosteum (^ c >-< pq 3 s THE LIMB MUSCLES 211 and chondroglossus, belong to the fourth or fifth branchiomere, although the remaining muscles of this physiological set are myo- tomic in origin. Finally, portions of two other muscles should probably he in- cluded in the list of branchiomeric muscles, these muscles being the trapezius and sternomastoid. It has already been seen that they are partly derived from the cervical myotomes, but they are also innervated in part by the spinal accessory, and since this nerve is really a special portion of the motor root of the vagus the muscles supphed by it should be regarded as branchiomeric in origin. The table on p. 210 shows the relations of the various cranial muscles to the myotomes and branchiomeres, as well as to the motor cranial nerves. The Limb Muscles. — It has been customary to regard the limb muscles as derivatives of certain of the myotomes, these structures in their growth ventrally in the trunk walls being supposed to pass out upon the postaxial surface of the limb buds and loop back again to the trunk along the praeaxial surface, each myotome thus giving rise to a portion of both the dorsal and the ventral muscu- lature of the limb. This view has not, however, been verified by direct observation of an actual looping of the myotomes over the axis of the limb buds; indeed, on the contrary, the limb muscles have been found to develop from the cores of mesenchyme which form the axes of the limb buds and from which the limb skeleton is also developed, and, furthermore, these axial cores can be traced back to an origin from the unsegmented ventral mesoderm, the adjacent myotomes having apparently no part in their formation. It seems proper, therefore, to regard the limb musculature as be- longing to a different^embryological category from the axial myo- tomic muscles, just as was the case of the branchiomeric musculature. The strongest evidence in favor of a myotomic origin of the limb muscles is that furnished by their nerve supply, this present- ing a distinctly segmental arrangement. This does not necessarily imply, however, a corresponding primarily metameric arrangement of the muscles, any more than the pronouncedly segmental ar- rangement of the cutaneous nerves implies a primary metamerism 212 THE LIMB MUSCLES of the dermis (see p. 145). It may mean only that the nerves, being segmental, retain their segmental relations to one another even in their distribution to non-metameric structures, and that, consequently, the limb musculature is supplied in succession from one border of the limb bud to the other from succeeding nerve roots. From this segmentally arranged innervation it is possible to recognize in the limb buds a series of parallel bands of muscle tr.d ^.ir vm Fig. 125. — Diagram of a Segment of the. Body and Limb. hi. Axial blastema; dm, dorsal musculature of trunk; rl, nerve to limb; s, septum between dorsal and ventral trunk musculature; sir. d, dorsal layer of limb muscula- ture; tr.d and Ir.v, dorsal and ventral divisions of a spinal nerve; vm, ventral muscu- lature of the trunk. — (Kollmann.) tissue, extending longitudinally along the bud and each supplied by a definite segmental nerve. And furthermore, corresponding to each band upon the ventral (praeaxial) surface of the limb bud, there is a band similarly innervated upon the dorsal (postaxial) surface, since the fibers which pass to the limb from each nerve root sooner or later arrange themselves in praeaxial and postaxial groups as is shown in the diagram Fig. 125. The first nerve which enters the limb bud lies along its anterior border, and consequently THE LIMB MUSCLES 213 the muscle bands which are supplied by it will, in the adult, lie along the outer side of the arm and along the inner side of the leg, in consequence of the rotation in opposite directions which the Hmbs undergo during development (see p. 104). Fig. 126. — External Surface of the Os Innominatum showing the Attach- ment OF Muscles and the Zones Supplied by the Various Nerves. 12, Twelfth thoracic nerve; / to V, lumbar nerves; i and 2, sacral nerves. — (Bolk.) The first nerve which supplies the muscle attached to the dorsum of the ilium is the second lumbar, and following that there come successively from before backward the remaining lumbar 214 THE LIMB MUSCLES and the first and second sacral nerves. The arrangement of the muscle bands supplied by these nerves and the muscles of the adult to which they contribute may be seen from Fig. 126. What is shown there is only the upper portions of the postaxial Fig. 127. — Sections through (A) the Thigh and (B) -the Calf showing THE Zones Supplied by the Nerves. The Nerves are Numbered in Con- tinuation with the Thoracic Series. — (A, after Bolk.) bands, their lower portions extending downward on the anterior surface of the leg. Only the sacral bands, however, extend throughout the entire length of the limb into the foot, the second lumbar band passing down only to about the middle of the thigh, THE LIMB MUSCLES 21$ the third to about the knee, the fourth to about the middle of the crus and the fifth as far as the base of the fifth metatarsal bone, and the same is true of the corresponding praeaxial bands, which descend from the ventral surface of the os coxae (innominatum) along the inner and posterior surfaces of the leg to the same points. The first and second sacral bands can be traced into the foot, the first giving rise to the musculature of its inner side and the second to that of its outer side, the praeaxial bands forming the plantar musculature, while the postaxial ones are upon the dorsum of the foot as a result of the rotation which the limb has undergone. In a transverse section through a limb at any level all the muscle bands, both praeaxial and postaxial, which descend to that level will be cut and will lie in a definite succession from one border of the limb to the other, as is seen in Fig. 127. In the differentia- tion of the individual muscles which proceeds as the nerves extend from the trunk into the axial mesenchyme of the limb, the muscle bands undergo modifications similar to those already described as occurring in the trunk myotomes. Thus, there has evidently been a longitudinal splitting of the original praeaxial muscle mass to form the various muscles of the back of the thigh; the soleus and gastrocnemius represent deep and superficial layers formed from the same bands by a horizontal (tangential) splitting; these same muscles contain a portion of the second sacral band which overlaps muscles composed only of higher bands; and the intermuscular septum between the peroneus brevis and the flexor hallucis longus represents a portion of the third sacral band which has degenerated into connective tissue. A similar arrangement occurs in the bands which are to be recognized in the musculature of the upper Hmb. These are sup- plied by the fourth, fifth, sixth, seventh and eighth cervical and the first thoracic nerves, and only those suppHed by the eighth cervical and the first thoracic nerves extend as far as the tips of the fingers. The arrangement of the bands in the upper part of the brachium may be seen from Fig. 128, in connection with which it must be noted that the fourth cervical band does not extend down to the level at which the section is taken and that the 2l6 THE LIMB MUSCLES praeaxial band of the eighth cervical nerve and both the praeaxial and postaxial bands of the first thoracic are represented only by connective tissue in this region. In another sense than the longitudinal one there is a division of the limb musculature into more or less definite areas, namely, in a transverse direction in accordance with the jointing of the skeleton. Thus, there may be recognized a group of muscles which pass from the axial skeleton to the limb girdle, another from the limb girdle to the brachium or thigh, another from the brachium Fig. 128. — Section through the Upper Part of the Arm showing the Zones Supplied by the Nerves. 5v to yv, Ventral branches; 5^ to 8d, dorsal branches of the cervical nerves. — (Bolk.) or thigh to the antibrachium or crus, another from the anti- brachium or crus to the carpus or tarsus, and another from the carpus or tarsus to the digits. This transverse segmentation if it may be so termed is not, however, perfectly definite, many muscles, even in the lower vertebrates, passing over more than one joint, and in the mammalia, especially, it is further obscured by secondary migrations, by the partial degeneration of muscles and by an end to end union of primarily distinct muscles. The latissimus dorsi, serratus anterior and pectoral muscles are all examples of a process of migration as is shown by their innervation from cervical nerves, as well as by the actual migration which has been traced in the developing embryo (Mall, Lewis). THE LIMB MUSCLES 21 7 In the lower limb evidences of migration may be seen in the femoral head of the biceps, comparative anatomy showing this to be a derivative of the gluteal set of muscles which has secondarily be- come attached to the femur and has associated itself with a prae- axial muscle to form a compound structure. An appearance of migration may also be produced by a muscle making a secondary attachment below its original origin or above the insertion and the upper or lower part, as the case may be, then degenerating into connective tissue. This has been the case with the peroneus longus, which, in the lower mammals, has a femoral origin, but has in man a new origin from the fibula, its upper portion being represented by the fibular lateral ligament of the knee-joint. So too the pectoralis minor is primarily inserted into the humerus, but it has made a secondary attachment to the coracoid process, its distal portion forming a coraco-humeral ligament. The comparative study of the flexor muscles of the anti- brachial and crural regions has yielded abundant evidence of ex- tensive modifications in the differentiation of the limb muscles. In the tailed amphibia these muscles are represented by a series of superposed layers, the most superficial of which arises from the humerus or femur, while the remaining ones take their origin from the ulna or fibula and are directed distally and laterally to be inserted either into the palmar or plantar aponeurosis, or, in the case of the deeper layers, into the radius (tibia) or carpus (tarsus). In the arm of the lower mammaha the deepest layer becomes the pronator quadratus, the lateral portions of the super- ficial layer are the flexor carpi ulnaris and the flexor carpi radialis, while the intervening layers, together with the median portion of the superficial one, assuming a more directly longitudinal direction, fuse to form a common flexor mass which acts on the digits through the palmar aponeurosis. From this latter structure and from the carpal and metacarpal bones five layers of palmar muscles take origin. The radial and ulnar portions of the most superficial of these become the flexor pollicis brevis and abductor pollicis brevis and the abductor quinti digiti, while the rest of the layer degenerates into connective tissue, forming tendons which 2l8 THE LIMB MUSCLES pass to the four ulnar digits. Gradually superficial portions of the antibrachial flexor mass separate off, carrying with them the layers of the palmar aponeurosis from which the tendons representing the superficial layer of the palmar muscles arise, and they form with these the flexor digitorum sublimis. The deeper layers of Pig. 129. — Transverse sections through (A) the forearm and (B) the hand show- ing the arrangement of the layers of the flexor muscles. The superficial layer is shaded horizontally, the second layer vertically, the third obliquely to the left, the fourth vertically, and the fifth obliquely to the right. AbM, abductor digiti quinti; AdP, adductor pollicis; BR, brachio-radialis ; ECD, extensor digtorum communis; ECU, extensor carpi ulnaris; EI, extensor indicis; EMD, extensor digiti quinti; EMP, abductor pollicis longus; ERB, extensor carpi radialis brevis; FCR, flexor carpi radialis; FCU, flexor carpi ulnaris; FLP, flexor pollicis longus; FM, flexor digiti quinti brevis; FP, flexor digitorum profundus; FS, flexor digitorum sublimis; ID interossei dorsales; IV, interossei volares; L, lumbricales; OM, opponens digiti quinti PL, palmaris longus; PT, pronator teres; R, radius; U, ulna; II-V, second to fifth metacarpal. of the antibrachial flexor mass become the flexor digitorum profundus and the flexor pollicis longus (Fig. 129, A), and retain their connection with the deeper layers of the palmar aponeurosis which form their tendons; and since the second layer of the palmar muscles takes origin from this portion of the aponeurosis it be- THE LIMB MUSCLES 219 comes the lumbrical muscles, arising from the profundus tendons (Fig. 129, B). The third layer of palmar muscles becomes the adductors of the digits, reduced in man to the adductor pollicis, while from the two deepest layers the interossei are developed. Of these the fourth layer consists primarily of a pair of slips cor- responding to each digit, while the fifth is represented by a series of muscles which extend obliquely across between adjacent meta- carpals. With these last muscles certain of the fourth layer slips Fig. 30. — Transverse sections through {A) the crus and (B) the foot, showing the arrangement of the layers of the flexor muscles. The shading has the same sig- nificance as in the preceding figure. A hH, abductor hallucis ; A bM, abductor minimi digiti; AdH, adductor hallucis; ELD, extensor longus digitorum; F, fibula; FBD flexor brevis digitorum; FBH, flexor brevis hallucis; FBM, flexor brevis minimi digiti; FLD, flexor longus digitorum; G, gastrocnemius; ID, interossei dorsales; IV, inter- ossei ventrales; L, lumbricales; P, plantaris; Fe, peroneus longus; Po, popliteus; S, soleus; T, tibia; TA, tibialis anticus; TP, tibialis posticus; I-V, first to fifth meta- tarsal. unite to form the dorsal interossei, while the rest become the volar interossei. The modifications of the almost identical primary arrange- ment in the crus and foot are somewhat different. The super- ficial layer of the crural flexors becomes the gastrocnemius and plantaris (Fig. 30, A) and the deepest layer becomes the popliteus and the interosseous membrane. The second and third layers unite to form a common mass which is inserted into the deeper layers of the plantar aponeurosis and later differentiates into the soleus and the long digital flexor, the former shifting its insertion from the plantar aponeurosis to the os calcis, while the flexor 220 LITERATURE retains its connection with the deeper layers of the aponeurosis, these separating from the superficial layer to form the long flexor tendons. The fourth layer assumes a longitudinal direction and becomes the tibialis posterior and the flexor hallucis longus and partly retains its original oblique direction and its connection with the deep layers of the plantar aponeurosis, becoming the quadratus plantse. In the foot (Fig. 129, B) the superficial layer persists as muscular tissue, forming the abductors, the flexor digitorum brevis and the medial head of the flexor hallucis brevis, the second layer becomes the lumbricales, and the third the lateral head of the flexor hallucis brevis and the abductor hallucis, while the fourth and fifth layers together form the interossei, as in the hand, the flexor quinti digiti brevis really belonging to that group of muscles. LITERATURE C. R. Bardeen and W. H. Lewis: "Development of the Limbs, Body- wall, and Back in Man," The American Journal of Anal., i, 1901. K. Bardeleben: "Muskel und Fascia" Jenaische Zeitschr. Jiir Naturwissensch., XV, 1882. L. BoLK: "Beziehungen zwischen Skelett, Muskulatur und Nerven der Extremitaten, dargelegt am Beckengiirtel, an dessen Muskulatur sowie am Plexus lumbo- sacralis," Morphol. Jahrhuch, xxi, 1894. L. Bolk: " Rekonstruktion der Segmentirung der Gliedmassenmuskulatur dargelegt an den Muskeln des Oberschenkels und des Schultergiirtels," Morphol. Jahrhuch, xxn, 1895. L. Bolk: "Die Sklerozonie des Humerus," Morphol. Jahrhuch, xxiii, 1896. L. Bolk: "Die Segmentaldifferenzierung des menschlichen Rumpfes und seiner Extremitaten," i, Morphol. Jahrhuch. xxv, 1898. R. Futamura: "Ueber die Entwickelung der Facialismuskulatur des Menschen," Anat. Hefte, xxx, 1906. E. Godlewski: "Die Entwicklung des Skelet- und Herzmuskelgewebes der Sauge- thiere," Archiv Jiir mikr., Anat. lx, 1902. E. Grafenberg: "Die Entwicklung der menschlichen Beckenmuskulatur," Anat. Hefte, xxin, 1904. W. P. Herringham: "The Minute Anatomy of the Brachial Plexus," Proceedings of the Royal Soc. London, xli, 1886. W. H. Lewis: "The Development of the Arm in Man," Amer. Journ. of Anat., i, 1902 J. B. MacCallum: "On the Histology and Histogenesis of the Heart Muscle-cell," A nat. A nzeiger, xiii, 1 89 7 . J. B. MacCallum: "On the Histogenesis of the Striated Muscle-fiber and the Growth of the Human Sartorius Muscle," Johns Hopkins Hospital Bulletin, 1898. LITERATURE 221 F. P. Mall: "Development of the Ventral Abdominal Walls in Man," Journ. of Morphol, XIV, 1898. Caroline McGill: "The Histogenesis of Smooth Muscle in the Alimentary Canal and Respiratory Tract of the Pig," Internal. Monatschr. Anat. und Phys., xxiv, 1907. J. P. McMurrich: "The Phylogeny of the Forearm Flexors," Amer. Journ. of Anat., II, 1903. J. P. McMurrich: "The Phylogeny of the Palmar Musculature," Amer. Journ. of Anat., II, 1903. J. P. McMurrich: "The Phylogeny of the Crural Flexors," Amer. Journ. of Anat, IV, 1904. • J. P. McMurrich: "The Phylogeny of the Plantar Musculature," Amer. Journ. of Anat.fYifigoy. A. Meek: "Preliminary Note on the Post-embryonal History of Striped Muscle- fibers in Mammalia," Anat. Anzeiger, xrv, 1898. (See also Anat. Anzeiger,xv, 1899.) B. MoRPURGo: "Ueber die post-embryonale Entwickelung der quergestreiften Muskel von weissen Ratten," Anat. Anzeiger, xv, 1899, I. Popowsky: "Zur Entwicklungsgeschichte des N. facialis beim Menschen," Morphol. Jahrhuch, xxiu, 1896. I. Popowsky: "Zur Entwickelungsgeschichte der Dammuskulatur beim Menschen," Anat. Hefte, xi, 1899. L. Rethi: "Der peripheren Verlauf der motorischen Rachen- und Gaumennerven," Sitzungsher. der kais. Akad. Wissensch. Wien. Math.-Naturwiss. Classe, cii, 1893. C. S. Sherrington: "Notes on the Arrangement of Some Motor Fibers in the Lumbo-sacral Plexus," Journal of Physiol., xiii, 1892. J. B. Sutton: "Ligaments, their Nature and Morphology," London, 1897. CHAPTER IX THE DEVELOPMENT OF THE CIRCULATORY AND LYMPHATIC SYTEMS At present nothing is known as to the earliest stages of de- velopment of the circulatory system in the human embryo, but it may be supposed that they resemble in their fundamental fea- tures what has been observed in such forms as the rabbit and the chick. It will be convenient to consider first the development of the first blood-vessels and of the blood, and later the formation of the heart and principal blood-vessels. In the rabbit the extension of the mesoderm from the embryo- nic region, where it first appears, over the yolk-sac is a gradual process, and it is in the more peripheral portions of the layer that the blood-vessels first make their appearance. They can be dis- tinguished before the splitting of the mesoderm has been com- pleted, but are always developed in that portion of the layer which is most intimately associated with the yolk-sac, and conse- quently becomes the splanchnic layer. They belong, indeed, to the deeper portion of that layer, that nearest the endoderm of the yolk-sac, and so characteristic is their origin from this portion of the layer that it has been termed the angiohlast and has been held to be derived from the endoderm independently of the meso- derm proper. The first indication of blood-vessels is the appear- ance in the peripheral portion of the mesoderm of cords or minute patches of spherical cells (Fig. 131, A). These increase in size by the division and separation of the cells from one another (Fig. 131, jB), a clear fluid appearing in the intervals which separate them. Soon the cells surrounding each cord arrange themselves to form an enclosing wall, and the cords, increasing in size, unite together to form a network of vessels in which float the spherical cells which may be known as haemohlasts. Viewed from the sur- 222 DEVELOPMENT OF THE BLOOD VESSELS 223 face at this stage a portion of the vascular area of the mesoderm would have the appearance shown in Fig. 132, revealing a dense network of canals in which, at intervals, are groups of haemo^ blasts adherent to the walls, constituting what have been termed the blood-islands, while in the meshes of the network unaltered mesoderm cells can be seen, forming the so-called substance-islands. Two views obtain as to the way in which the extension of the vascularization process from the extra embryonic-regions into the body of the embryo takes place. In one the angioblast is given Fig. 131. — Transverse Sections through the Area Vasculosa of Rabbit Embryos showing the Transformation of Mesoderm Cells into the Vascular Cords, Ec, Ectoderm; En, endoderm; Me, mesoderm. — (van der Stricht.) the status of an additional germ-layer, distinct from the mesoderm; it is a specific tissue, set apart at an early stage of the develop- ment as the origin of all the vascular apparatus, endotheUum and blood elements, of the embryo, and it is the sole source of this apparatus. Hence the vascular tissue of the embryo proper is formed by the extension into the embryo of angioblastic material from the extra-embryonic regions, the vascular endotheUum is a specific tissue and the embryonic mesenchyme has no part in its formation, According to the other view such specificity is denied the angioblast and it is held that vasifactive tissue may be formed locally from the embryonic mesenchyme; the angioblast is merely ?24 DEVELOPMENT OF THE BLOOD VESSELS extra-embryonic mesenchyme that has assumed a vasifactive func- tion, and by processes similar to those shown by it the mesenchyme of practically any part of the embryo proper may become con- verted into vascular tissue, producing vascular networks which eventually unite directly or in- directly with those formed by the angioblast. Briefly, according to this view, there is not neces- sarily immediate genetic contin- uity of all the vascular endothe- lium, but mesenchyme cells in any region of the body may become endothelium and conversely en- dothelial cells under certain condi- tions may revert to mesenchyme. Whichever of these views eventually proves to be correct the end result is that the blood vascular system, both in its em- bryonic and extra-embryonic por- tions, consists in its earlier stages of a continuous network of vessels Hned with endothelium and con- taining haemoblasts formed by the multiplication of the original haemoblasts and by proliferation from the endothelial cells them- selves. Later, enlargements of the network develop along more or less definite lines to form the heart, the arteries and veins, other portions of it persist to form the capillaries, while others again disappear entirely. The differentiation of blood-vessels from the network on the surface of the yolk-sac of a rabbit embryo is shown at its commencement in Fig. 133, A and in Fig. 133, B the exten- sion of the differentiation has resulted in the formation of a sinus terminalis, a vitelline artery and two vitelline veins. Fig. 132. — Surface View of a Portion of the Area Vasculosa OF A Chick. The vascular network is represented by the shaded portion. Bi, Blood- island; Si, substance-island. — (Disse.) DEVELOPMENT OF THE BLOOD VESSELS 225 In the human embryo the sHght development of the yolk-sac and the increased importance of the chorion in the nutrition of the embryo have apparently led to a reduction in the development"" of the vitelline network and an acceleration in the development of the chorionic vessels (see p. 118), but otherwise the early develop- ment of the blood-vascular system is probably similar to what has been described for the rabbit. —^^''A Fig. 133. — The Vascular Areas- of Rabbit Embryos. In B the Veins are Represented by Black and the Network is Omitted. — (von Beneden and Julin.) It is to be noted that the capillary network of the area vascu- losa consists of relatively wide anastomosing spaces whose endo- thehal lining rests directly upon the substance islands (Fig. 131). In certain of the embryonic organs, notably the liver, the meta- nephros and the heart, when these have become vascularized, the network has a similar character, consisting of wide anastomos- ing spaces bounded by an endothelium which rests directly, or almost so, upon the parenchyma of the organ (the hepatic cylin- ders, the mesonephric tubules, or the cardiac muscle trabeculae) (Figs. 134 and 191, ^). To this form of capillary the term sinusoid has been applied (Minot), and it appears to be formed by the expansion of the wall of a previously existing blood-vessel, which thus moulds itself, as it were, over the parenchyma of the organ. 15 2 26 THE FORMATION OF THE BLOOD The true capillaries, on the other hand, are more definitely tubular in form, are usually imbedded in mesench\Tnatous connective tissue, but are developed in the same manner as the primary capillaries of the area vasculosa, by the aggregation of vasifactive cells to form cords, and the subsequent hollowing out of these. The Formation of the Blood. — The haemoblasts, which are the first formed blood-corpuscles are all nucleated and destitute or nearly so of haemoglobin. They have been held by some observers to be the only source of the various forms of corpuscles that are found in the adult vessels, while others maintain that they give rise only to the red corpuscles, the leukocytes arising in tissues external to the blood-vessels and only secondarily making their way into them. According to this latter view the red and white corpuscles have a different origin and remain distinct throughout life. However this may be, it is certain that the haemoblasts and the erythrocytes that are formed from them increase by division in the interior of the embryo, and that there are certain portions of the body in which these divisions take place most abundantly, partly, perhaps, on account of the more favorable conditions of nutrition which they present and partly because they are regions where the circulation is sluggish and permits the accumulation of erythro- cytes. These regions constitute what have been termed the hamatopoietic organs, and are especially noticeable in the later stages of fetal life, diminishing in number and variety about the time of birth. It must be remembered, however, that the life of individual corpuscles is comparatively short, their death and disintegration taking place continually during the entire life of the individual, so that there is a necessity for the formation of new corpuscles and for the existence of haematopoietic organs at all stages of life. In the fetus haemoblasts in process of division may be found in the general circulation and even in the heart itself, but they are much more plentiful in places where the blood-pressure is diminished, as, for instance, in the larger capillaries of the lower limbs and in the capillaries of all the visceral organs and of the THE FORMATION OF THE BLOOD 227 subcutaneous tissues. Certain organs, however, such as the liver, the spleen, and the bone-marrow, present especially favorable conditions for the multiplication of the blood-cells, and in these- not only are the capillaries enlarged, so as to afford resting-places for the corpuscles, but gaps appear in the walls of the vessels through which the blood-elements may pass and so come into intimate relations with the actual tissues of the organs (Fig. 154). After birth the haematopoietic function of the Uver ceases and that of the spleen becomes limited to the formation of white corpuscles^ though the complete function ^_ ^_^ may be re-established in cases ^ of extreme anaemia. The bone marrow, however, retains the function completely, being throughout life the seat of for- mation of both red and white corpuscles, the lymphatic nodes and foUicles, as well as the spleen, assisting in the for- mation of the latter elements. The haemoblasts early be- come converted into nucleated red corpuscles or erythrocytes by the development of haemo- globin in their cytoplasm, their nuclei at the same time becom- ing granular. Up to a stage at which the embryo has a length of about 112 mm. these are the only form of red corpuscle in the circulation, but at this time (Minot) a new form, characterized by its smaller size and more deeply staining nucleus, makes its appearance. These erythrocytes have been termed normoblasts (Ehrhch), although they are merely transition stages leading to the forma- tion of erythroplastids by the extrusion of their nuclei (Fig. 135). The cast-off nuclei undergo degeneration and phagocytic absorp- tion by the leukcocytes, and the masses of cytbplasm pass into Fig. 134. — Section of a Portion of thb Liver of a Rabbit Embryo of 5 mm. e. Erythrocytes in the liver substance and in a capillary; h, hepatic cells. — {van der Stricht.) 228 THE FORMATION OF THE BLOOD the circulation, becoming more and more numerous as develop- ment proceeds, until finally they are the typical haemoglobin- containing elements in the blood and form what are properly termed the red blood-corpuscles. It has already (p. 226) been pointed out that discrepant views prevail as to the origin of the white blood-corpuscles . Indeed, three distinct modes of origin have been assigned to them. According to one view they have a common origin with the erythrocytes from the haemoblasts (Weidenreich), according to another they are formed from mesenchyme cells out- side the cavities of the blood-vessels (Maximow), while according to a third view the first formed leukocytes take their origin from the endodermal epitheHal cells of the thymus gland (Prenant). 9 &€)(§) Fig. 135. — Stages in the Transformation of an Erythro- cyte INTO AN ErYTHROPLASTID. (van der Stricht.) Fig. 136. — Figures of the Different Forms of White Corpuscles occurring IN Human Blood. ■ a, Lymphocytes; h, finely granular (neutrophile) leukocyte; c, coarsely granu- lar (eosinophile) leukocyte; d, polymorphonuclear (basophile) leukocyte. — (Weiden- reich.) But whatever may be their origin, in later stages the leukocytes multiply by mitosis and there is a tendency for the dividing cells to collect in the lymphoid tissues, such as the lymph nodes, tonsils, THE FORMATION OF THE BLOOD 229 etc., to form more or less definite groups which have been termed germ-centers (Flemming). The new cells when they first pass into the circulation have a relatively large nucleus surrounded by aT small amount of cytoplasm without granules and, since they re- semble the cells found in the lymphatic vessels, are termed lymphocytes (Fig. 136, a). In the circulation, however, other forms of leukocytes also occur, which are beheved to have their origin from cells with much larger nuclei and more abundant cytoplasm, which occur throughout life in the bone-marrow and Fig. 137. — Megacaryocyte from a Kitten, which has Extended Two PSEUDOPODIAL PROCESSES THROUGH THE WaLL OF BlOOD-VESSEL AND IS BUDDING OFF Blood-platelets. hp, Blotfd-platelets; V, blood-vessel. — {J. H. Wright.) have been termed myelocytes. Cells of a similar type, free in the circulation, constitute what are termed the finejy granular leuko- cytes {neutrophile cells of Ehrlich) (Fig. 135, b), but whether these and the myelocytes are derived from lymphocytes or have an independent origin is as yet undetermined. Less abundant are the coarsely granular leukocytes (eosinophile cells of Ehrlich) Fig. 136, c), characterized by the coarseness and staining reactions of their cytoplasmic granules and by their reniform or constricted nucleus. They are probably derivatives of the finely granular type and it has been maintained by Weidenreich that their granules have been acquired by the phagocytosis of degenerated 230 THE FORMATION OF THE HEART erythrocytes. Finally, a third type is formed by the poly- morphonuclear or polynudear leukocytes (basophile cells of Ehrlich) (Fig. 136, d)j which are to be regarded as leukocytes in the process of degeneration and are characterized by their irregularly lobed or fragmented nuclei, as well as by their staining peculiarities. In the fetal haematopoietic organs and in the bone-marrow of the adult large, so-called giant-cells are found, which, although they do not enter into the general circulation, are yet associated with the development of the blood-corpuscles. These giant-cells as they occur in the bone-marrow are of two kinds which seem to be quite distinct, although both are probably formed from leukocytes. In one kind the cytoplasm contains several nuclei, whence they have been termed polycaryocyteSj and they seem to be the cells which have already been mentioned as osteoclasts (p. 160). In the other kind (Fig. 137) the nucleus is single, but it is large and irregular in shape, frequently appearing as if it were producing buds. These megacaryocytes appear to be phagocytic cells, having as their function the destruction of degenerated corpuscles and of the nuclei of the erythrocytes. The blood-platelets have recently been shown by Wright to be formed from the cytoplasm of the megacaryocytes, by the constric- tion and separation of portions of the slender processes to which they give rise in their amoeboid movements (Fig. 137). They have also been described as forming in a similar manner from leukocytes and even from the endothehal cells of the blood vessels (Jordan). The Formation of the Heart. — The heart makes its appearance while the embryo is still spread out upon the surface of the yolk sac, and arises as two separate portions which only later come into contact in the median Une. On each side of the body near the margins of the embryonic area a fold of the splanchnopleure appears, projecting into the coelomic cavity, and within this fold is a thin-walled sac, probably representing an enlargement of the primitive angioblastic network (Fig. 138, A). Each fold will produce a portion of the muscular walls (myocardium) of the heart and each sac part of its endothehum (endocardium). As the THE FORMATION OF THE HEART 231 constriction of the embryo from the yolk-sac proceeds, the two folds are gradually brought nearer together (Fig. 13^, B), until they meet in the mid-ventral Hne, when the myocardial folds and en Fig. 138. — Diagrams Illustrating the Formation of the Heart in the Guinea- pig. The mesoderm is represented in black and the endocardium by a broken line, am. Amnion; en, endoderm; h, heart; i, digestive tract. — (After Strahl and Carius.) endocardial sacs fuse together (Fig. 13^, C) to form a cylindrical heart lying in the mid-ventral line of the body, in front of the anterior surface of the yolk-sac and in what will later be the 232 THE FORMATION OF THE HEART cervical region of the body. At an early stage the various veins which have already been formed, the vitellines, umbilicals, jugu- lars and cardinals, unite together to open into a sac-like structure, the sinus venosus, and this opens into the posterior end of the heart cylinder. The anterior end of the cylinder tapers off to form the aortic bulb, which is continued forward on the ventral surface of the pharyngeal region and carries the blood away from the heart. The blood accordingly opens into the posterior end of the heart tube and flows from its anterior end. Fig. 139. — Heart of Embryo of 2.15 MM., FROM A Reconstruction. a. Atrium; ab, aortic bulb; d, dia- phragm; dc, ductus Cuvieri; /, liver; V, ventricle; vj, jugular vein; vu, um- bilical vein. — (His.) Fig. 140. — Heart of Embryo of 4.2 MM., SEEN from THE DORSAL Surface. DC, Ductus Cuvieri; lA, left atrium; rA, right atrium; vj, jugular vein; VI, left ventricle; vu, umbilical vein. — (His.) The simple cylindrical form soon changes, however, the heart tube in embryos of 2.15 mm. in length having become bent upon itself into a somewhat S-shaped curve (Fig. 139). Dorsally and to the left is the end into which the sinus venosus opens, and from this the heart tube ascends somewhat and then bends so as to pass at first ventrally and then caudally and to the right, where it again bends at first dorsally and then anteriorly to pass over into THE FORMATION OF THE HEART 233 the aortic bulb. The portion of the curve which lies dorsally and to the left is destined to give rise to both atria, the portion which passes from right to left represents the future left ventricle7 while the succeeding portion represents the right ventricle. In later stages (Fig. 140) the left ventricular portion drops down- ward in front of the atrial portion, assuming a more horizontal position, while the portion which represents the right ventricle is drawn forward so as to lie in the same plane as the left. At the same time two small out-pouchings develop from the atrial part of the heart and form the first indications of the two ^n,fJ^^ atria. As development pro- gresses, these increase in size to form large pouches opening into a common atrial canal (Fig. 141) which is directly continuous with the left ventricle, and as the enlargement of the pouches con- tinues their openings into the canal enlarge, until finally the pouches become continuous with one another, forming a single large sac, and the atrial canal becomes reduced to a short tube which is slightly invaginated into the ventricle (Fig. 142). In the meantime the sinus venosus, which was originally an oval sac and opened into the atrial canal, has elongated trans- versely until it has assumed the form of a crescent whose convexity is in contract with the walls of the atria, and its opening into the heart has verged toward the right, until it is situated entirely within the area of the right atrium. As the enlargement of the atria continues, the right horn and median portion of the crescent are gradually taken up into their walls, so that the various veins which originally opened into the sinus now open directly into the right atrium by a single opening (Fig. 143) guarded on either side by a projecting fold, these folds being continued upon the roof Fig. 141. — Heart of Embryo of 5 MM., Seen from in Front and slightly from Above. — '{His.) 234 THE FORMATION OF THE HEART of the atrium as a muscular ridge, known as the septum spurium (Fig. 42, sp). The left horn of the crescent is not taken up into the atrial wall, but remains upon its posterior surface as an elon- gated sac, forming the coronary sinus. The division of the now practically single atrial cavity into the permanent right and left atria begins with the formation of a falciform ridge running dorso-ventrally across the roof of the cavity. This is the atrial septum or septum primum (Fig. 142 Fig. 142. — Inner Surface of the Heart of an Embryo of 10 mm. al, Atrio-venticular thickening; sp, septum spurium; ss, septum prim am; sv, septum ventriculi; ve. Eustachian valve. — {His.) ss), and it rapidly increases in size and thickens upon its free margin, which reaches almost to the upper border of the short atrial canal (Fig. 144). The continuity of the two atria is thus almost dissolved, but is soon re-established by the formation in the dorsal part of the septum of an opening which soon reaches a considerable size and is known as the foramen ovale (Fig. 14^, fo). Close to the atrial septum, and parallel with it, a second ridge ap- pears in the roof and ventral wall of the right atrium. This septum secundum (Fig. 143, 5^) is of relatively slight development THE FORMATION OF THE HEART 235 Sr S2 in the human embryo, and its free edge, arching around the ventral edge and floor of the foramen ovale, becomes continuous with the left Kp of the fold which guards the opening of the sinus— venosus and with this forms the annulus of Vieussens of the adult heart. When the absorption of the sinus venosus into the wall of the right atrium has proceeded so far that the veins communicate directly with the atrium, the vena cava superior opens into it at the upper part of the dorsal wall, the vena cava inferior more laterally, and below this ^fe the smaller opening of the coronary sinus. The upper portion of the right lip of the fold which originally surrounded the opening of the sinus venosus, together with the septum spurium, gradually disappears; the lower portion persists, however, and forms (i) the Eustachian valve (Fig. 143, Ve), guarding the opening of the inferior cava and directing the blood entering by it toward the foramen ovale, and (2) the Thebesian valve, which guards the open- ing of the coronary sinus. At first no veins communicate with the left atrium, but on the development of the lungs and the establishment of their vessels, the pulmonary veins make connection with it. Two veins arise from each lung, and asthey pass toward the heart they unite in pairs, the two vessels so formed again uniting to form a single short trunk which opens into the upper part of the atrium (Fig. 144, Vep). As is the case with the right atrium and the sinus venosus, the expansion of the left atrium brings about the absorption of the short single trunk into its walls, and, the expansion continuing, the two vessels are also absorbed, so that eventaully the four pri- mary veins open independently into the atrium. While the atrial septa have been developing there has appeared Fig. 143. — Heart of Em- bryo OF 10.2 CM. FROM WHICH Half of the Right Auricle HAS BEEN Removed] /o, Foramen ovale; pa, pulmonary artery; Si septum primum; Si, septum sec- undum; Sa, systemic aorta; V, right ventricle; vci and vcs, inferior and superior venae cavae; Ve, Eustachian valve. 236 THE FORMATION OF THE HEART on the dorsal wall of the atrial canal a tubercle-like thickening of the endocardium, and a similar thickening also forms on the ventral wall. These endocardial cushions increase in size and finally unite together by their tips, forming a complete parti- tion, dividing the atrial canal into a right and left half (Fig. 144). SM En.s Bw^ Fig. 144. — Section through a Reconstruction of the Heart of a Rabbit Embryo of 10. i mm. Ad and Adi, Right and As, left atrium; Bwi and Bw2, lower ends of the ridges which divide the aortic bulb; En, endocardial cushion; En.r and En.s, thickenings of the cushion; la, interatrial and Iv, interventricular communication; Si, septum primum; Sd, right and 55, left horn of the sinus venosus; S.iv, ventricular septum; SM, opening of the sinus venosus into the atrium; Vd, right and Vs, left ventricle; Vej, jugular vein; Vep, pulmonary vein; Vvd and Vvs, right and left limbs of the valve guarding the openings of the sinus venosus. — (Born.) With the upper edge of this partition the thickened lower edge of the atrial septum unites, so that the separation of the atria would be complete were it not for the foramen ovale. While these changes have been taking place in the atrial por- THE FORMATION OF THE HEART 237 tion of the heart, the separation of the right and left ventricles has also been progressing, and in this two distinct septa take part. From the floor of the ventricular cavity along the line of junction" of the right and left portions a ridge, composed largely of muscular tissue, arises (Figs. 142 and 144), and, growing more rapidly in its dorsal than its ventral portion, it comes into contact and fuses with the dorsal part of the partition of the atrial canal. Ventrally, however, the ridge, known as the venrHcular septum, fails to reach the ventral part of the partition, so that an oval foramen, situated just below the point where the aortic bulb arises, still remains between the two ventricles. This opening is finally closed by what is termed the aortic septum. This makes its appearance in the aortic bulb just at the point where the first lateral branches which give origin to the pulmonary arteries (see p. 245) arise, and is formed by the fusion of the free edges of two endocardial ridges which develop on opposite sides of the bulb. From its point of origin it gradually extends down the bulb until it reaches the ventricle, where it fuses with the free edge of the ventricular septum and so completes the separation of the two ventricles (Fig. 145). The bulb now consists of two vessels lying side by side, and owing to the position of the partition . at its anterior end, one of these vessels, that which opens into the right ventricle, is continuous with the pulmonary arteries, while the other, which opens into the left ventricle, is continuous with the rest of the vessels which arise from the forward continuation of the bulb. As soon as the development of the partition is com- pleted, two grooves, corresponding in position to the lines of at- tachment of the partition on the inside of the bulb, make their appearance on the outside and gradually deepen until they finally meet and divide the bulb into two separate vessels, one of which is the pulmonary aorta and the other the systemic aorta. In the early stages of the heart's development the muscle bundles which compose the wall of the ventricle are very bosely arranged, so that the ventricle is a somewhat spongy mass of muscular tissue with a relatively small cavity. As development proceeds the bundles nearest the outer surface come closer to- 238 THE FORMATION OF THE HEART gether and form a compact layer, those on the inner surface, how- ever, retaining their loose arrangement for a longer time (Fig. S.Tir App T :Fa?:d Fay.s - - — Sw -Vs S.ivr Fig. 145. — Diagrams of Sections through the Heart of Embryo Rabbits TO Show the Mode of Division of the Ventricles and of the Atrio-ventricu- lar Orifice. Ao, Aorta; Ar.p, pulmonary artery; B, aortic bulb; Bw2 and *, one of the ridges which divide the bulb; Eo, and Eu, upper and lower thickenings of the margins of the atrio-ventricular orifice; F.av.c, the original atrio-ventricular orifice; F.av.d and F.av.s, right and left atrio-ventricular orifices; Oi, interventricular communication; 5. iv, ventricular septum; Vd and Vs, right and left ventricles. — {Born.) 144). The lower edge of the atrial canal becomes prolonged on the left side into one, and on the right side into two, flaps which project ' downward into the ventricular cavity, and an additional THE FORMATION OF THE HEART 239 flap arises on each side from the lower edge of the partition of the atrial canal, so that three flaps occur in the right atrio-ven- tricular opening and two in the left. To the under surfaces of these flaps the loosely arranged muscular trabeculae of the ventricle are attached, and muscular tissue also occurs in the flaps. This condition is transitory, however; the muscular tissue of the flaps degenerates to form a dense layer of connective tissue, and at the same time the muscular trabeculae undergo a condensation. Some of them separate from the flaps, which represent the atrio-ventricu- lar valves, and form muscle bundles which may fuse throughout their entire length with the more compact portions of the ventricu- PiG. 146. — Diagrams showing the Development of the Auriculo-ventricular Valves. b, Muscular trabeculae; cht, chordae tendineae; mk and mk^, valve; pm, musculus papillaris; tc, trabeculae carneae; v, ventricle. — (From Hertwig, after Gegenbaur.) lar walls, or else may be attached only by their ends, forming loops; these two varieties of muscle bundles constitute the tra- heculcB carnecB of the adult heart. Other bundles may retain a transverse direction, passing across the ventricular cavity and forming the so-called moderator hands; while others, again, re- taining their attachment to the valves, condense only at their lower ends to form the musculi papillares, their upper portions undergoing conversion into strong though slender fibrous cords, the chordm tendinece (Fig. 146). The endocardial lining of the ventricles is at first a simple sac separated by a distinct interval from the myocardium, but when the condensation of the muscle trabeculae occurs the endocardium applies itself closely to the irregular surface so formed, dipping 240 THE PORMATION OF THE HEART into all the crevices between the trabeculae carneae and wrapping itself around the musculi papillares and chordae tendinae so as to form a complete lining of the inner surface of the myocardium. In early stages the myocardial tissue of the atria is continuous with that of the ventricles throughout the entire circumference of the wall of the atrial canal, but later this wall becomes converted into connective tissue and the continuity is interrupted, except in the region behind the posterior endocardial cushion. Here a band of the original tissue persists and eventually forms the atrichventricular bundle. The aortic and pulmonary semilunar valves make their appearance, before the aortic bulb undergoes its longitudinal split- ting, as four tubercle-Uke thickenings of con- nective tissue situated on the inner wall of the bulb just where it arises from the ventricle. When the division of the bulb occurs, two of the thickenings, situated on opposite sides, are divided, so that both the pulmonary and systemic aortae recfcive three thickenings (Fig. 147). Later the thickenings become hollowed out on the surfaces directed away from the ventricles and are so converted into the pouch-like valves of the adult. Changes in the Heart after Birth. — The heart when first formed lies far forward in the neck region of the embryo, between the head and the anterior surface of the yolk-sac, and from this posi- tion it gradually recedes until it reaches its final position in the thorax. And not only does it thus change its relative position, but the direction of its axes also changes. For at an early stage the ventricles lie directly in front of {i.e., ventrad to) the atria and not below 'them as in the adult heart, and this primitive condition is retained until the diaphragm has reached its final position (see p. 325). In addition to these changes in position, which are antenatal, important changes also occur in the atrial septum after birth. Throughout the entire period of fetal life the foramen ovale Fig. 147. — Dia- grams Illustrating THE Formation of the Semilunar Valves. — (fiegenhaur.) DEVELOPMENT OF THE ARTERIAL SYSTEM 241 persists, permitting the blood returning from the placenta and entering the right atrium to pass directly across to the left atrium, thence to the left ventricle, and so out to the body through the systemic aorta (see p. 268). At birth the lungs begin to function and the placental circulation is cut off, so that the right atrium receives only venous blood and the left only arterial; a persistence of the foramen ovale beyond this period would be injurious, since it would permit of a mixtue of the arterial and venous bloods, and, consequently, it closes completely soon after birth. The closure is made possible by the fact that during the growth of the heart in size the portion of the atrial septum which is between the edge of the foramen ovale and the dorsal wall of the atrium increases in width, so that the foramen is carried further and further away from the dorsal wall of the atrium and comes to be almost com- pletely overlapped by the annulus of Vieussens (Fig. 143). This process continuing, the dorsal portion of the atrial septum finally overlaps the free edge of the annulus, and after birth the fusion of the overlapping surfaces takes place and the foramen is com- pletely closed. In a large percentage (25 to 30 per cent.) of individuals the fusion of the surfaces of the septum and annulus is not complete, so that a slit- like opening persists between the two atria. This, however, does not 'allow of any mingling of the blood in the two cavities, since when the atria contract the pressure of the blood on both sides will force the overlapping folds together and so practically close the opening. Occa- sionally the growth of the dorsal portion of the septum is imperfect or is inhibited, in which case closure of the foramen ovale is impossible. The Development of the Arterial System.— It has been seen (p. 222) that the formation of the blood-vessels begins in the extra- embryonic splanchnic mesoderm surrounding the yolk-sac and ex- tends thence toward the embryo. Furthermore, it has been seen that the vessels appear as capillary networks from which definite stems are later elaborated. This seems also to be the method of formation of the vessels developed within the body of the embryo, the arterial and venous stems being .first represented by a number of anastomosing capillaries, from which, by the enlargement of 16 242 DEVELOPMENT OF THE ARTERIAL SYSTEM some and the disappearance of the others, the definite stems are formed. The earliest known embryo that shows a blood circulation is that described by Eternod (Fig. 44). From the plexus of vessels on the yolk-sac two veins arise which unite with two other veins returning from the chorion by the belly-stalk and passing forward to the heart as the two umbihcal veins (Fig. 148, Vu). There is as yet no vitelline vein, the chorionic circulation in the human Fig. 148. — Diagram showing the Arrangement of the Blood-vessels in an Embryo 1.3 mm. in Length. Au, Umbilical artery; All, allantois; Ch, chorionic villus; dAr and dAs, right and left dorsal aortae; Vu, umbilical veins; Ys, yolk-sac. — (From Kollmann after Eternod.) embryo apparently taking precedence over the vitelline. From the heart a short arterial stem arises, which soon divides so ?s to form three branches* passing dorsally on either side of the phar- ynx. The branches of each side then unite to form a paired dorsal * Evans (Keibel-Mall, Human Embryology, Vol. n, 191 2) considers two of these branches to be probably plexus formations rather than definite stems, since there is evidence to indicate that only one such stem exists at such an early stage of development. DEVELOPMENT OF THE ARTERIAL SYSTEM 243 aorta (dAr, dAs) which extends caudally and is continued into the belly-stalk and so to the chorion as the umbiHcal arteries (Au). There is as yet no sign of vitelline arteries passing to the yolk-sac, again an indication of the subservience of the vitelline to the chorionic circulation in the human embryo. In later stages when the branchial arches have appeared the dorsally directed arteries are seen to he in these, forming what are termed the branchial arch vessels, and later also the two dorsal aortae fuse as far forward as the region of the eighth cervical segment to form a single trunk from which segmental branches arise. It will be convenient to con- sider first the history of the ves- sels which pass dorsally in the branchial arches. Altogether, six of these vessels are devel- oped, the fifth rudimentary and transitory, and when fully formed they have an arrangement which may be understood from the dia- gram (Fig. 149). This arrange- ment represents a condition which is permanent in the lower verte- brates. In the fishes the respiration is performed by means of gills developed upon the branchial arches, and the heart is an organ which receives venous blood from the body and pumps it to the gills, in which it becomes arterialized and is then collected into the dorsal aortae, which distribute it to the body. But in terrestrial animals ,' with the loss of gills and the development of the lungs as respiratory organs, the capillaries of the gills disappear and the afferent and efferent branchial vessels become continuous, the condition represented in the diagram resulting. Fig. 149. — Diagram Illustrating THE Primary Arrangement of the Branchial Arch Vessels. ■ a. Aorta; ab, aortic bulb; ec, external carotid; ic, internal carotid; sc, sub- clavian; I-VI, branchial arch vessels. 244 DEVELOPMENT OF THE ARTERIAL SYSTEM But this condition is merely temporary in the mammalia and numerous changes occur in the arrangement of the vessels before the adult plan is realized. The first change is a disappearance of the vessels of the first arch, the ventral stem from which it arose being continued forward to form the temporal arteries, giving off near the point where the branchial vessel originally arose a branch which represents the internal maxillary artery in part, and possibly also a second branch which represents the external maxillary (His). A little later the second branchial vessel also degenerates (Fig. Pig. ISO. — Arterial System of an Embryo of io mm. Ic, Internal carotid; P, pulmonary artery; Ve, vertebral artery; /// to VI, persistent branchial vessels. — (His.) 150), a branch arising from the ventral trunk near its former origin, possibly representing the future lingual artery (His), and then the portion of the dorsal trunk which intervenes between the third and fourth branchial vessels vanishes, so that the dorsal trunk anterior to the third branchial arch is cut off from its con- nection with the dorsal aorta and forms, together with the vessel of the third arch, the internal carotid, while the ventral trunk, anterior to the point of origin of the third vessel, becomes the external carotid, and the portion which intervenes between the third and fourth vessels becomes the common carotid (Fig. 151). The rudimentary fifth vessel, like the first and second, dis- DEVELOPMENT OF THE ARTERIAL SYSTEM 245 appears, but the fourth persists to form the aortic arch, there being at this stage of development two complete aortic arches. From the sixth vessel a branch arises which passes backward to unite with a network of vessels which extends downwards to the region of the lungs and is formed in cat embryos by the an- astomosis of branches from the upper six segmental branches of the dorsal aortae (Huntington). From this network the pulmonary artery eventually differen- tiates and, its connections with the segmental aortic branches dissolving, it ap- pears to be a direct down- growth from the sixth arch. The portion of the right sixth arch that intervenes between the point of origin of the pulmonary artery and the right aortic arch disap- pears, while the correspond- ing portion of the left side persists until after birth, forming the ductus arteriosus (ductus Botalli) (Fig. 151). When the longitudinal di- vision of the aortic bulb occurs (p. 237), the septum is so arranged as to place the sixth arch in communication with the right ventricle and the remain- ing vessels in connection with the left ventricle, the only direct communication between the systemic and pulmonary vessels being by way of the ductus arteriosus, whose significance will be explained later (p. 269). One other change is still necessary before the vessels acquire Fig. 151. — Diagram Illustrating the Changes in the Branchial Arch Vessels. a. Aorta; da, ductus arteriosus; ec, ex- ternal carotid; ic, internal carotid; pa, pulmonary artery; sc, subclavian; I-IV, aortic arch vessels. 246 DEVELOPMENT OF THE ARTERIAL SYSTEM the arrangement which they possess during fetal life, and this consists in the disappearance of the lower portion of the right aortic arch (Fig. 151), so that the left arch alone forms the con- nection between the heart and the dorsal aorta. The upper part of the right aortic arch persists to form the proximal part of the right subclavian artery, the por- tion of the ventral trunk which unites the arch with the aortic bulb becoming the innominate artery. From the entire length of the thoracic aorta, and in the embryo from the aortic arches, lateral -i [- ;^ \ 1] n.^ branches arise corresponding to 3 C M , /^^ ^ ^^^^ segment and accompanying the segmental nerves. The first of these branches arises just be- low the point of union of the vessel of the sixth arch with the dorsal trunk and accompanies the hypoglossal nerve (Fig. 152, /f), and that which accom- panies the seventh cervical nerve arises just above the point of union of the two aortic arches (Fig. 152, s), and extends out into the Hmb bud, forming the subclavian artery.* Further down twelve pairs of lateral branches, arising from the thoracic portion of the aorta, represent the intercostal arteries, and still lower four pairs of lumbar arteries are formed, the fifth lumbars being represented by two large branches, the common * It must be remembered that the right subclavian of the adult is more than equivalent to the left, since it represents the fourth branchial vessel -f- a portion of the dorsal longitudinal trunk -1- the lateral segmental branch (see Fig. 144). iCo. IM Fig. 152. — Diagram showing the Relations of the Lateral Branches TO the Aortic Arches. EC, External carotid; h, lateral branch accompanying the hypoglossal nerve; /C, internal carotid; ICo, inter- costal; IM, internal mammary; s, sub- clavian; V, vertebral; /to VIII, lateral cervical branches; i, 2, lateral thoracic branches. DEVELOPMENT OF THE ARTERIAL SYSTEM 247 iliacs, which seem from their size to be the continuations of the aorta rather than branches of it. The true continuation of the aorta is, however, the middle sacral artery, which represents in a" degenerated form the caudal prolongation of the aorta of other mammals, and, like this, gives off lateral branches corresponding to the sacral segments. In addition to the segmental lateral branches arising from the aorta, visceral branches, which have their origin rather from the Fig. 153. — Diagram showing the Arrangement of the Segmental Branches ARISING from the AoRTA, A. Aorta; B, lateral somatic branch; C, lateral visceral branch; D, median visceral branch; E, peritoneum. ventral surface, also occur. In embryos of 5 mm. these branches are arranged in a segmental manner in threes, a median unpaired vessel passing to the digestive tract and a pair of more lateral branches passing to the mesonephros (see p. 342), corresponding to each of the paired branches passing to the body wall (Fig. 153). As development proceeds the great majority of these visceral branches disappear, certain of the lateral ones persisting, however, to form the renal, internal spermatic, and hypogastric arteries of the adult, while the unpaired branches are represented only 248 DEVELOPMENT OF THE ARTERIAL SYSTEM by the coeliac artery and the superior and inferior mesenteries. The superior mesenteric artery is the adult representative of the vitelline artery of the embryo and arises from the aorta by two, three or more roots, v\rhich correspond to the fifth, fourth and higher thoracic segments. Later, all but the lowest of the roots disappear and the persisting one undergoes a downward migra- tion in accordance with the recession of the diaphragm and viscera (see p. 325) until in embryos of 1 7 mm. it lies opposite the first lumbar segment. Sim- ilarly the coeliac and inferior mesenteric arteries, which when first recognizable in em- bryos of 9 mm. correspond with the fourth and twelfth thoracic segments respect- ively, also undergo a second- ary downward migration, the coeHac artery in embryos of 17 mm. arising opposite the twelfth thoracic and the in- ferior mesenteric opposite the third lumbar segment. The umbilical arteries of the embryo seem at first to be the direct continuations of the dorsal aortae (Fig. 148), but as development proceeds they come to arise from the aorta opposite the third lumbar segment, where they are in line with the lateral visceral segmental branches. They pass ventral to the Wolffian duct (see p. 341) and are continued out along with the allantois to the chorionic villi. Later this original stem is joined, not far from its origin, by what appears to be the lateral somatic branch of the fifth lumbar segment, whereupon the proximal part of the original^ umbilical vessel degenerates and the umbilical comes to arise from the somatic branch which is the common iliac artery Fig. 154. — Diagram Illustrating the Development of the Umbilical Arteries. A, Aorta; CIl, common iliac; Ell, ex- ternal iliac; G, gluteal; ///, internal iliac; IP, internal pudic; IV, inferior vesical; Sc, sciatic; U, umbilical; U', primary proximal portion of the umbilical ; wd. Wolffian duct. DEVELOPMENT OF THE ARTERIAL SYSTEM 249 of adult anatomy (Fig. 154). Hence it is that this vessel in the adult gives origin both to branches such as the external iliac, the gluteal, the sciatic and the internal pudendal, which are distrib- uted to the body walls or their derivatives, and to others, such as the vesical, inferior haemorrhoidal and uterine, which are dis- tributed to the pelvic viscera. At birth the portions of the um- bilical arteries beyond the umbilicus are severed when the umbiHcal cord is cut, and their intraembryonic portions, which have been called the hypogastric arteries, quickly undergo a reduction in size. Their proximal portions remain functional as the superor vesical arteries, carrying blood to the urinary bladder, but the portions which intervene between the bladder and the umbilicus become reduced to solid cords, forming the obliterated hypogastric arteries of adult anatomy. In its general plan, accordingly, the arterial system may be regarded as consisting of a pair of longitudinal vessels which fuse together throughout the greater portion of their length to form the dorsal aorta, from which there arise segmentally arranged lateral somatic branches and ventral and lateral visceral branches. With the exception of the aortic trunks (together with their an- terior continuations, the internal carotids) and the external caro- tids, no longitudinal arteries exist primarily. In the adult, however, several longitudinal vessels, such as the vertebrals, internal mammary, and epigastric arteries, exist. The formation of these secondary longitudinal trunks is the result of a develop- ment between adjacent vessels of anastomoses, which become larger and more important blood-channels than the original vessels . At an early stage each of the lateral branches of the dorsal aorta gives off a twig which passes forward to anastomose with a back- wardly directed twig from the next anterior lateral branch, so as to form a longitudinal chain of anastomoses along each side of the neck. In the earliest stage at present known the chain starts from the lateral branch corresponding to the first cervical (suboccipital) segment and extends forward into the skull through the foramen magnum, terminating by anastomosing with the internal carotid. To this original chain other links are added from each of the sue- 250 DEVELOPMENT OF THE ARTERIAL SYSTEM ceeding cervical lateral branches as far back as the seventh (Pigs. 152 and 155). But in the meantime the recession of the heart toward the thorax has begun, with the result that the common carotid stems are elongated and the aortic arches are apparently Avcb. ISp.G. Avcv Pig. 155. — The Development of the Vertebral Artery in a Rabbit Embryo OF Twelve Days. IIIA.B to VIA.B, Branchial arch vessels; Ap, pulmonary artery. A.v.c.b and A.v.cv, cephalic and cervical portions of the vertebral artery; A.s, subclavian; C.d and C.v internal and external carotid; ISp.G, spinal ganglion. — (Hochstetter.) shortened so that the subclavian arises on the left side almost opposite the point where the aorta was joined by the sixth bran- chial vessel. As this apparent shortening proceeds, the various lateral branches which give rise to the chain of anastomoses, with the exception of the seventh, disappear in their proximal por- DEVELOPMENT OF THE ARTERIAL SYSTEM 25 1 tions and the chain becomes an independent stem, the vertebral artery, arising from the seventh lateral branch, which is the sub- clavian. The recession of the heart is continued until it lies below the level of the upper intercostal arteries, and the upper two of these, together with the last cervical branch on each side, lose their con- nection with the dorsal aorta, and, sending off anteriorly and pos- teriorly anastomosing twigs, develop a short longitudinal stem, the costo-cervical trunk, which opens into the subclavian. Fig. 156. — Embryo of 13 mm. showing the Mode of Development of the In- ternal Mammary and Deep Epigastric Arteries. — {Mall.) The intercostals and their abdominal representatives, the lumbars and ihacs, also give rise to longitudinal anastomosing twigs near their ventral ends (Fig. 156), and these increasing in size give rise to the internal mammary and inferior epigastric arteries, which together form continuous stems extending from the subclavians to the external iliacs in the ventral abdominal walls. The superficial epigastrics and other secondary longitudi- nal vessels are formed in a similar manner. 252 DEVELOPMENT OF ARTERIES OF LIMBS The Development of the Arteries of the Limbs. — The earliest stages in the development of the Umb arteries are unknown in man, but it has been found that in the mouse the primary supply of the anterior limb bud is from five branches arising from the sides of the aorta. These anastomose to form a plexus from which later a single stem, the subclavian artery, is elaborated, occupying the position of the seventh cervical segmental vessel, the remaining branches of the plexus having disappeared. The common iliac artery similarly represents the fifth lumbar segmental artery, but whether or not it also is elaborated from a plexus is as yet unknown. The later history of the limb arteries is also but imperfectly known and one must rely largely upon the facts of comparative anatomy and on the anomalies that occur in the adult for indica- tions of what the development is likely to be. The comparative evidence indicates the existence of several stages in the develop- ment of the Hmb vessels, and so far as embryological observations go they confirm the conclusions drawn from this source, although the various stages show apparently a great amount of overlapping owing to a concentration of the developmental stages. In the simplest arrangement the subclavian is continued as a single trunk along the axis of the limb as far as the carpus, where it divides into digital branches for the fingers. In its course through the fore- arm it Hes in the interval between the radius and ulna, resting on the interosseous membrane, and in this part of its course it may be termed the arteria interossea. In the second stage a new artery accompanying the median nerve appears, arising from the main stem or brachial artery a little below the elbow-joint. This may be termed the arteria mediana, and as it develops the arteria inter- ossea gradually diminishes in size, becoming finally the small volar interosseous artery of the adult (Fig. 157), and the median, uniting with its lower end, takes from it the digital branches and becomes the principal stem of the forearm. A third stage is then ushered in by the appearance of a branch from the brachial which forms the arteria ulnaris, and this, passing down the ulnar side of the forearm, unites at the wrist with the DEVELOPMENT OF ARTERIES OF LIMBS 253 median to form a superficial palmar arch from which the digital branches arise. A fourth stage is marked by the diminution of the- median artery until it finally appears to be a small branch of the interosseous, and at the same time there develops from the bra- chial, at about the middle of the upper arm, what is known as the A Fig. 157. — Diagrams showing an Early and a late Stage in the Development OF THE Arteries of the Arm. h. Brachial; i, interosseous; rw, median; r, radial; rs, superficial radial; u, ulnar. arteria radialis super ficialis (Fig. 157, rs). This extends down the radial side of the forearm, following the course of the radial nerve, and at the wrist passes upon the dorsal surface of the hand to form the dorsal digital arteries of the thumb and index finger. At first this artery takes no part in the formation of the palmar arches, but later it gives rise to the superficial volar branch, which usually unites with the superficial arch, while from its dorsal portion a 254 DEVELOPMENT OF ARTERIES OF LIMBS perforating branch develops which passes between the first and second metacarpal bones and unites with a deep branch of the ulnar to form the deep arch. The fifth or adult stage is reached by the development from the brachial below the elbow of branch (Fig. 157, r) which passes downward and outward to unite with the superficial radial, whereupon the upper portion of that artery degenerates until it is represented only by a branch to the biceps •/ ^gi e Fig. 158. — Diagram illustrating the Development of the Arteries of the Leg. For the sake of Simplicity the Femoral Rete is Omitted. (After Senior) . ci. Inferior; cm, middle; cs, superior communicating branch; dp, dorsal plexus; /, femoral; gi, inferior gluteal; I, interosseous; P.popliteus muscle; pc, perforating erural; pe, peroneal; pf, profunda femoris; po, popliteal; pp, plantar plexus; ps, superficial peroneal; pi, peforating tarsal; s, sciatic; ta, anterior tibial; tp, posterior tibial. muscle (Schwalbe), while the lower portion persists as the adult radial. The various anomalies seen in the arteries of the forearm are, as a rule, due to the more or less complete persistence of one or other of the DEVELOPMENT OF ARTERIES OF LIMBS 255 stages described above, what is described, for instance, as the high branching of the brachial being the persistence of the superficial radial^ In the leg there is a noticeable difference in the arrangement of the arteries from what occurs in the arm, in that the principal artery of the thigh, the femoral, does not accompany the principal nerve, the sciatic. This condition and the adult arrangement of the crural vessels have been found to be the result of a number of somewhat complicated changes (Senior), the more important of which are diagrammatically represented in Fig. 1 58. In the simplest stage, which is to be seen in embryos of 8.0-10.0 mm., a single artery extends down the back of the leg, passing anterior to the popliteus muscle and thence being continued down the crus on the interosseous membrane, to terminate in a plantar network, a branch (Fig. 158 ^, pt) passing through the tarsus to join a dorsal network. The upper part of this artery may be termed the sciatic, while its crural portion may be spoken of as the interrosseous. The femoral at this stage is represented by a network of vessels, the femoral reie, which extends throughout the entire length of the thigh and with which the sciatic communicates by a branch passing between the adductor magnus and the femur (Fig. 158, B, Cs), In a later stage the superficial femoral and the profunda femoris differentiate from the femoral rete, the former being continuous with the branch of the sciatic that passes through the adductor magnus. From the sciatic a branch (po), which becomes the popliteal artey of the adult, passes down over the posterior surface of the popliteus, immediately below that muscle sending a branch (cm) to communicate with the interosseous, and divides a little lower down to form two vessels, one of which represents the posterior tibial (/^), while the other may be termed the superficial peroneal (ps). From this last a communicating branch (ci), extends downwards to join the lower part of the interosseous, from whose upper part a branch (pc) passes forward through the interosseous membrane and thence down the crus as the anterior tibial (ta) to join the dorsal network. The plantar network is now connected with the interosseous, the superficial 256 DEVELOPMENT OF THE VENOUS SYSTEM peroneal and the posterior tibial, but the perforating tarsal branch which united it with the dorsal network has disappeared. This represents a condition from which the adult arrangement is formed by the disappearance of certain vessels (Fig. 158, C). Almost the whole of the sciatic vanishes, its uppermost portion persisting, however, to form the inferior gluteal (gi) and the branch of that vessel which accompanies the sciatic nerve, while a small portion of it, just where it joined the perforating crural branch, is retained to form the medial articular artery of the knee. The upper part of the interosseous also disappears, its lower part persisting as a portion of the adult peroneal (pe), the upper part of which is formed by what was the communicating branch (ci) between the interosseous and the superficial peroneal, this latter artery vanishing. The terminal lateral calcaneal portion of the peroneal is a new formation and a perforating branch from the interosseous passes forward, through the lower part of the inter- osseous membrane, to join the anterior tibial. The dorsalis pedis and its branches are differentiated from the original dorsal network, while the plantar arteries are similarly derived from the plantar network. The Development of the Venous System. — The earliest veins to develop are those which accompany the first-formed arteries, the umbilicals, but it will be more convenient to consider first the veins which carry the blood from the body of the embryo back to the heart. These make their appearance, while the heart is still in the pharyngeal region, as two pairs of longitudinal trunks, the anterior and posterior cardinal veins, into which lateral branches, arranged more or less segmentally, open. The anterior cardinals appear somewhat earlier than the posterior and form the internal jugular veins of adult anatomy. In the head each vein passes along the side of the brain as the vena capitis prima, passing medial to the root of the trigeminus but lateral to the origins of the more posterior cranial nerves and receiving aff erents from three plexuses which extend dorsally over the walls of the brain iii the substance of the dura mater (Fig. 159 and 160, A). In embryos of about 20 mm. the anterior and middle plexuses have united (Fig. 160, C) DEVELOPMENT OF THE VENOUS SYSTEM 257 and have developed a new pathway for their discharge, which passes backwards dorsal to the! ear capsule to join the posterior plexus, through which it reaclfes the jugular foramen. At the same time the posterior portion of the vena capitis prima dis- appears (Fig. 160, B and C), that portion of it, however, which passes medial to the trigeminus root persisting, since it receives an fjcl pcv Fig. 159. — Reconstruction of the Head of a Human Fmbryo of 9 mm. showing THE Cerebral Veins. acv, Anterior cerebral vein; au, auditory vesicle; cs, cavernous sinus; fa, facial nerve; mcv, middle cerebral vein; pcv, posterior cerebral vein; tr, trigeminal nerve; vcv, lateral cerebral vein. — (Mall.) from in front the opthalmic vein which has developed from the more anterior portions of the anterior plexus. This persisting portion of the vena capitis prima becomes the cavernous sinus of the adult and now drains into the trunk that passes dorsal to the ear capsule, by a vessel which represents the superior petrosal sinus of the adult. Later the superior sagittal sinus is differ- entiated from the dorsal portions of the anterior plexuses (Fig. 17 258 DEVELOPMENT OF THE VENOUS SYSTEM PLEXUS. MECXALIS PLEXUS MEStALIS B PLEXUS ANT BIN. RECTUS SIN. SAGITTALIS SUP PLEXUS ANT SIN. TRANSVERSUS SIN. SAGnTALIS SUP SIN. SAGITTALIS SUP. ^ "% SIN. RECTUS f »^ CONFLUENS SINUUM /W__ W \ SIN. TRANS ^T^""^?^ "^f^ ) .IN. cavern;^ /^ > (pars SIGMOID, S PETROSINF. / \W\ 7 Ts. PETROS SUP ji / / y i ri 1 INT SIN. SAGITTALIS E F Fig. i6o.— Six Stages in the Development of the Sinuses of the Dura Mater. {SireeUr). DEVELOPMENT OF THE VENOUS SYSTEM 250 1 60 D), while the straight and inferior sagittal sinuses are elabor- ated from those portions of the plexuses which extend down be- tween the two cerebral hemispheres in the falx cerebri; and since" the superior sagittal and straight sinuses open into the trunk which passes dorsal to the ear capsule, it is now clear that this trunk represents the transverse sinus of adult anatomy. The essential features of the adult arrangement are now completed by the formation of the inferior petrosal sinus (Fig. 160 D), this being practically a reconstitution of the posterior portion of the original vena capitis prima, and the various parts of the cerebral system of veins are brought into their adult relations by the straightening out of the nape bend and by the continued growth of the cerebral hemispheres. (Fig. 160, E and F). Passing backward from the jugular foramen the internal jugu- lar veins unite with the posterior cardinals to form on each side a common trunk, the ductus Cuvieri, which passing transversely to- ward the median Hne, opens into the side of the sinus venosus. So long as the heart retains its original position in the pharyngeal region the jugular is a short trunk receiving lateral veins only from the uppermost segments of the neck and from the occipital seg- ments, the remaining segmental veins opening into the inferior cardinals. As the heart recedes, however, the jugulars become more and more elongated and the cervical lateral veins shift their communication from the cardinals to the jugulars, until, when the subclavians have thus shifted, the jugulars become much larger than the cardinals. When the sinus venosus is absorbed into the wall of the right auricle, the course of the left Cuvierian duct be- comes a little longer than that of the right, and from the left jugu- lar, at the point where it is joined by the left subclavian, a branch arises which extends obliquely across to join the right jugular, forming the left innominate vein. When this is established, the connection between the left jugular and Cuvierian duct is dis- solved, the blood from the left side of the head and neck and from the left subclavian vein passing over to empty into the right jugular whose lower end, together with the right Cuvierian duct, thus be- comes the superior vena cava. The left Cuvierian duct persists 26o DEVELOPMENT OF THE VENOUS SYSTEM forming with the left horn of the sinus venosus the coronary sinus (Fig. i6i). The external jugular vein develops somewhat later than the internal. The facial vein, which primarily forms the principal affluent of this stem, passes at first into the skull along with the fifth nerve and communicates with the internal jugular system, but later this original communication is broken and the facial vein, uniting with other superficial veins, passes over the jaw and ex- tends down the neck as the external jugular. Later still the facial Fig. i6i, — Diagrams showing the Development of the Superior Vena Cava. a, Azygos vein; cs, coronary sinus; ej, external jugular; h, hepatic vein, ij, internal jugular; inr and inl, right and left innominate veins; s, subclavian; vci and vcs, in- ferior and superior venae cavae. anastomoses with the ophthalmic at the inner angle of the eye and also makes connections with the internal jugular just after it has crossed the jaw, and so the adult condition is acquired. It is interesting to note that in many of the lower mammals the external jugular becomes of much greater importance than the internal, the latter in some forms, indeed, eventually disappearing and the blood from the interior of the skull emptying by means of anastomoses which have developed into the external jugular system. In man the primi- tive condition is retained, but indications of a transference of the intracranial blood to the external jugular are seen in the emissary veins. The posterior cardinal veins, or, as they may more simply be termed, the cardinals, extend backward from their union with the DEVELOPMENT OF THE VENOUS SYSTEM 261 jugulars along the sides of the vertebral column, receiving veins from the mesentery and also from the various lateral segmental veins of the neck and trunk regions, with the exception of that or the first cervical segment which opens into the jugular. Later, however, as already described (p. 259), the cervical veins shift to the jugulars, as do also the first and second thoracic (intercostal) veins, but the remaining intercostals, together with the lumbars and sacrals, continue to open into the cardinals. In addition, the cardinals receive in early stages the veins from the primitive kid- neys (mesonephros), which are exceptionally large in the human embryo, but as they become replaced later on by the permanent kidneys (metanephros) their afferent veins undergo a reduction in number and size, and this, together with the shifting of the upper lateral veins, produces a marked diminution in the size of the car- dinals. The changes by which they acquire their final arrange- ment are, however, so intimately associated with the development of the inferior vena cava that their description may be conven- iently postponed until the history of the vitelline and umbilical veins has been presented. The vitelline veins are two in number, a right and a left, and pass in along the yolk-stalk until they reach the embryonic intestine, along the sides of which they pass forward to unite with the corre- sponding umbilical veins. These are represented in the belly- stalk by a single venous trunk which, when it reaches the body of the embryo, divides into two stems which pass forward, one on each side of the umbilicus, and thence on each side of the median line of the ventral abdominal wall, to form with the corresponding vitelline veins common trunks which open into the ductus Cuvieri. As the liver develops it comes into intimate relation with the vitel- line veins, which receive numerous branches from its substance and, indeed, seem to break up into a network (Fig. 162, A) tra- versing the liver substance and uniting again to form two stems which represent the original continuations of the vitellines. From the point where the common trunk formed by the right vitel- line and umbilical veins opens into the Cuverian duct a new vein develops, passing downward and to the left to unite with the left 262 DEVELOPMENT OF THE VENOUS SYSTEM vitelline; this s the ductus venosus (Fig. 162, B, D.V.A.). In the meantime three cross-connections have developed between the two vitelline veins, two of which pass ventral and the other dorsal to the intestine, so that the latter is surrounded by two venous loops (Fig. 163, ^), and a connection is developed between each umbilical vein and the corresponding vitelline (Fig. 162, B), that of the left side being the larger and uniting with the vitelHne just where it is joined by the ductus venosus, so as to seem to be the continua- tion of this vessel (Fig. 162, C)./^When these connections are jDC, DC Vus. Vo.m.s DC ~2?.KA PTus U^v^ Vud VoTTl^d. VOTJVS. Fig. 162. — Diagrams Illustrating the Transformations of the Vitelline AND Umbilical Veins. D.5, Ductus Cuvieri; D.V.A, ductus venosus; V .o.m.d and V .o.m.s, right and left vitelline veins; V .u.d and V .u.s, right and left umbilical veins. — (Hochstetter.) complete, the upper portions of the umbilical veins degenerate (Fig. 163), and now the right side of the lower of the two vitelline loops which surround the intestine disappears, as does also that portion of the left side of the upper loop which intervenes between the middle cross-connection and the ductus venosus, and so there is formed from the vitelline veins the vena portce. While these changes have been progressing the right umbilical vein, originally the larger of the two (Fig. 162, A and B, V.u.d.), has become very much reduced in size and, losing its connection with the left vein at the umbilicus, forms a vein of the ventral ab- DEVELOPMENT OF THE VENOUS SYSTEM 263 dominal wall in which the blood now flows from above downward. The left umbilical now forms the only route for the return of blood from the placenta, and appears to be the direct continuation of the ductus venosus (Fig. 163, C), into which open the hepatic veins ^ re- turning the blood distributed by the portal vein to the substance of the liver. Returning now to the posterior cardinal veins, it has been found that in the rabbit the branches which come to them from the mesentery anastomose longitudinally to form a vessel lying parallel Fig. 163. — A, the Venous Trunks of an Embryo of 5 mm. seen from the Ventral Surface; B, Diagram Illustrating the Transformation to the Adult Cono tion. Vcd and Vcs, Right and left superior venae cavas; Vj, jugular vein; V.om, vitelline vein; Vp, vena portae; Vu, umbilical vein (lower part); Vu', umbilical vein (upper part); Vud and Vus, right and left umbilical veins (lower parts). — (His.) and slightly ventral to each cardinal. These may be termed the subcardinal veins (Lewis), and in their earliest condition they open at either end-4nto the corresponding cardinal, with which they are also united by numerous cross-branches. Later, in rabbits of 8.8 mm., these cross-branches begin to disappear and give place to a large cross-branch situated immediately below the origin of the superior mesenteric artery, and at the same point a cross branch between the two subcardinals also develops. The portion of the 264 DEVELOPMENT OF THE VENOUS SYSTEM right subcardinal which is anterior to the cross-connection now rapidly enlarges and unites with the ductus venosus about where the hepatic veins open into that vessel (Fig. 164 A), and the por- tion of each posterior cardinal immediately above the entrance of the renal veins degenerates, so that all the blood received by the posterior portions of the cardinals is returned to the heart by way of the right subcardinal, its cross-connections, and the upper part of the ductus venosus. Fig. 164. — Diagrams Illustrating the Development of the Inferior Vena Cava. The cardinal veins and ductus venosus are black, the subcardinal system blue, and the supracardinal yellow, cs, coronary sinus; dv, ductus venosus; il, iliac vein; r, renal; s, internal spermatic; scl, subclavian; sr, suprarenal; va, azygos;vha, hemi- azygos; vi, innominate; vj, internal jugular. When this is accomplished the lower portions of the subcardi- nals disappear, while the portions above the large cross-connec- tion persist, greatly diminished in size, as the suprarenal veins (Fig. 164, B). In the early stages the veins which drain the posterior abdomi- nal walls empty into the posterior cardinals, and later they form, in DEVFXOPMENT OF THE VENOUS SYSTEM 265 the region of the kidney on each side, a longitudinal anastomosis which opens at either extremity into the posterior cardinal. The_ ureter thus becomes surrounded by a venous ring, the dorsal limb of which is formed by the new longitudinal anastomosis, which has been termed the supracardinal vein (McClure and Huntington) while the ventral Kmb is formed by a portion of the posterior cardinal (Fig. 164, B). Still later the ventral limb of the loop disappears and the dorsal supracardinal Hmb replaces a portion of the more primitive posterior cardinal. An anastomosis now develops between the right and left cardinals at the point where the iliac veins open into them (Fig. 163, -B), and the portion of the left cardinal which intervenes between this anastomosis and the entrance of the internal spermatic vein disappears, the remainder of it, as far forward as the renal vein, persisting as the upper part of the left internal spermatic vein, which thus comes to open into the renal vein instead of into the vena cava as does the corre- sponding vein of the right side of the body (Fig. 164, C,j). The renal veins originally open into the cardinals at the point where these are joined by the large cross-connection, and when the lower part of the left cardinal disappears, this cross-connection forms the proximal part of the left renal vein, which consequently receives the left suprarenal (Fig. 164, C). The observations upon which the above description is based have been made chiefly upon the rabbit and pig, but it seems pro- bable from the partial observations that have been made that sim- lar changes occur also in the human embryo. It will be noted from what has been said that the inferior vena cava is a composite vessel, consisting of at least four elements: (i) the proximal part of the ductus venosus; (2) the anterior part of the right sub- cardinal; (3) the right supracardinal; and (4) the posterior part of the right cardinal. The complicated development of the inferior vena cava naturally gives rise to numerous anomalies of the vein due to inhibitions of its development. These anomalies affect especially the post-renal portion a persistence of both cardinals (interpreting the conditions in the terms of what occurs in the rabbit) giving rise to a double post-renal 266 DEVELOPMENT OF THE VENOUS SYSTEM cava, or a persistence of the left cardinal and the disappearance of the right to a vena cava situated on the left side of the vertebral column and crossing to the right by way of the left renal vein. So, too the occurrence of accessory renal veins passing dorsal to the ureter is ex- plicable on the supposition that they represent portions of the supra- cardinal system of veins. It has already been noted that the portions of the posterior cardinals immediately anterior to the entrance of the renal veins disappear. The thoracic portion of the right vein persists, how- ever, and becomes the vena azygos of the adult, while the upper portion of the left vein sends a cross-branch over to unite with the azygos and then separates from the coronary sinus to form the vena hemiazygos. At least this is what is described as occur- ring in the rabbit. In the cat, however, only the very uppermost portion of the right posterior cardinal persists and the greater portion of the azygos and perhaps the entire hemizaygos vein is formed from the prerenal portions of the supracardinal veins, the right one joining on to the small persisting upper portion of the right posterior cardinal, while the cross-connection between the hemiazygos and azygos represents one of the originally numerous cross-connections between the supracardinals. The ascending lumbar veins, frequently described as the commence- ments of the azygos veins, are in reality secondary formations de- veloped by the anastomoses of anteriorly and posteriorly directed branches of the lumbar veins. The Development of the Veins of the Limbs. — The development of the limb veins of the human embryos requires further investiga- tion, but from a comparison of what is known with what has been observed in rabbit embryos it may be presumed that the changes which take place are somewhat as follows: In the anterior ex- tremity the blood brought to the limb is collected by a vein which passes distally along the radial border of the limb bud, around its distal border, and proximally along its ulnar border to open into the anterior cardinal vein; this is the primary ulnar vein. Later a second vein grows out from the external jugular along the radial border of the limb, representing the cephalic vein of the adult, and on its appearance the digital veins, which were formed from the THE FETAL CIRCULATION 267 primary ulnar vein, becomes connected with it, and the distal portion of the primary ulnar vein disappears. Its proximal por- tion persists, however, to form the basilic vein, from which the brachial vein and its continuation, the ulnar vein, are developed, while the radial vein develops as an outgrowth from the cephalic, which at an early stage secures an opening into the axillary vein, its original communication with the external jugular forming the jugulo-cephalic vein. In the lower limb a primary fibular vein, exactly comparable to the primary ulnar of the arm, surrounds the distal border of the limb-bud and passes up its fibular border to open with the poste- rior cardinal vein. The further development in the lower limb dif- fers considerably, however, from that of the upper limb. From the primary fibular vein an anterior tibial vein grows out, which re- ceives the digital branches from the toes, and from the posterior cardinal, anterior to the point where the primary fibular opens into it, a vein grows down the tibial side of the leg, forming the long saphenous vein. From this the femoral vein is formed and from it the posterior tibial vein is continued down the leg. An anastomo- sis is formed between the femoral and the primary fibular veins at the level of the knee and the proximal portion of the latter vein then becomes greatly reduced, while its distal portion possibly persists as the small saphenous vein (Hochstetter). The Pulmonary Veins. — The development of the pulmonary veins has already been described in connection with the develop- ment of the heart (see p. 235). The Fetal Circulation. — During fetal life while the placenta is the sole organ in which occur the changes in the blood on which the nutrition of the embryo depends, the course of the blood is neces- sarily somewhat different from what obtains in the child after birth. Taking the placenta as the starting-point, the blood passes along the umbiHcal vein to enter the body of the fetus at the umbili- cus, whence it passes forward in the free edge of the ventral mesen- tery (see p. 324) until it reaches the liver. Here, owing to the anastomoses between the umbiHcal and vitelHne veins, a portion of the blood traverses the substance of the liver to open by the hepat- 268 THE FETAL CIRCULATION ic veins into the inferior vena cava, while the remainder passes on through the ductus venosus to the cava, the united streams open- ing into the right atrium. This blood, whose purity is only slightly reduced by mixture with the blood returning from the in- -vJ; Fig. 165. — The Fetal Circulation. ao, Aorta; a.pu., pulmonary artery; au, umbilical artery; da, ductus arteriosus; dv, ductus venosus; int, intestine; vci and vsc, inferior and superior vena cava; vh, hepatic vein; vp, vena portae; v.pu, pulmonary vein; vu, umbilical vein. — (From Kollmann.) f erior vena cava, is prevented from passing into the right ventricle by the Eustachian valve, which directs it to the foramen ovale, and through this it passes into the left atrium, thence to the left ventricle, and so out by the systemic aorta. THE FETAL CIRCULATION 269 The blood which has been sent to the head, neck, and upper extremities is returned by the superior vena cava also into the right atrium, but this descending stream opens into the atrium to right of the annulus of Vieussens (see Fig. 143) and passes directly to the right ventricle without mingling to any great extent with the blood returning by way of the inferior cava. From the right ven- tricle this blood passes out by the pulmonary artery; but the lungs at this period are collapsed and in no condition to receive any great amount of blood, and so the stream passes by way of the ductus arteriosus into the systemic aorta, meeting there the placental blood just below the point where the left subclavian artery is given off. From this point onward the aorta contains only mixed blood, and this is distributed to the walls of the thorax and ab- domen and to the lungs and abdominal viscera, the greater part of it, however, passing off in the hypogastric arteries and so out again to the placenta. This is the generally accepted account of the fetal circulation and it is based upon the idea that the foramen ovale is practically a con- nection between the inferior vena cava and the left atrium. If it be correct the right ventricle receives only the blood returning to the heart by the vena cava superior, while the left receives all that returns by the inferior vena cava together with what returns by the pulmonary veins. One would, therefore, expect that the capacity and pressure of the right ventricle would in the fetus be less than those of the left. Pohlman, who has recently investigated the question in embryo pigs, finds, on the contrary, that the capacities and pressures of the two ventricles are equal and maintains that the foramen ovale is actually a connection between the two atria. That is to say, he holds that there is an actual mingling of the blood from the two venae cavae in the right atrium, whence the mixed blood passes to the right ventricle, a certain amount of it, however, passing through the foramen ovale and so to the left ventricle to equalize the deficiency that would otherwise exist in that chamber owing to the small amount of blood returning by the pulmonary veins. According to this view there would be no difference in the quality of the blood distributed to different portions of the body, such as is provided for by the current theory; all the blood leaving the heart would be mixed blood and in favor of this view is the fact that starch granules injected into either the superior or the inferior vena cava in living pig embryos were in all cases re- covered from both sides of the heart. . 270 DEVELOPMENT OF THE LYMPHATIC SYSTEM At birth the lungs at once assume their functions, and on the cutting of the umbilical cord all communication with the placenta ceases. Shortly after birth the foramen ovale closes more or less perfectly, and the ductus arteriosus diminishes in size as the pul- monary arteries increase and becomes eventually converted into a fibrous cord. The hypogastric arteries diminish greatly, and after they have passed the bladder are also reduced to fibrous cords, a fate likewise shared by the umbilical vein, which becomes con- verted into the round ligament of the liver. The Development of the Lymphatic System. — The lymphatic system is associated with the blood-vascular system both in its adult condition and in its development. Indeed, at one stage it is virtually a part of the blood-vascular system, being represented by capillary networks hardly distinguishable from adjacent blood capillaries, containing blood like these and being connected with neighboring venous trunks. These networks are developed in definite regions of the body, one being formed in relation with the proximal portion of each anterior cardinal (internal jugular) vein, another pair appearing along the lines of the iliac veins, while another, unpaired, develops in the root of the mesentery along the line of the median vein draining the mesonephros (see p. 342). In later stages the vessels forming these networks dilate and unite together to form sac-like structures, termed lymph sacs, which are accordingly five in number, i.e., two jugular (Fig. 166, ALH), two iliac (Fig. 166, PLH) and one retroperitoneal (Fig. 167 Isr). At first these lymph sacs still contain blood and are con- nected with the neighboring venous trunks, but later they evacuate their blood contents and separate from the veins, forming inde- pendent sacs lined by endothelium. In relation with these as centers the remaining portions of the lymphatic system, the tho- racic duct and the peripheral vessels, develop, the sacs themselves eventually becoming transformed into groups of lymphatic nodes, the jugular ones, however, re-establishing connections between the lymphatic and venous systems by uniting with the junctions of the jugular and subclavian veins. With regard to the development of the thoracic duct and per- DEVELOPMENT OF THE LYMPHATIC SYSTEM 271 ipheral vessels, as well as with regard to the first formation of the primary networks from which the lymph sacs develop, two dis-_ cordant views exist. According to one (Sabin, Lewis) the net- works are formed by the union of a number of outgrowths from Fig. 166. — Diagrams showing the Arrangement of the Lymphatic Vessels in Pig Embryos of (A) 20 mm. and (B) 40 mm. ACV, Jugular vein; ADR, suprarenal body; ALH, jugular lymph sac; Ao, aorta? Arm D, deep lymphatics to the arm; D, diaphragm; Du, branches to duodenum; FV, femoral vein; H, branches to heart; K, kidney; Leg D, deep lymphatics to leg; Lu, branches to lung; MP, branches to mesenteric plexus; CE, branch to oesophagus; PCV, cardinal vein; PLH, posterior lymph sac; RC, cisterna chyli; RLD, right lymphatic duct; ScV, subclavian vein; SV, sciatic vein; St, branches to stomach; TD, thoracic duct; WB, Wolffian body. — (Sabin.) the veins and the peripheral vessels are formed by a process of budding from the lymph sacs, outgrowths of the endothelium of 272 DEVELOPMENT OF THE LYMPHATIC SYSTEM these radiating into the surrounding mesenchyme. From the jugular sacs are formed the vessels which drain the upper half of each side of the body and the arms, from the iliac sacs those drain- ing the walls of the lower half of each side of the body, the perma- nent kidneys and the legs, and from the retroperitoneal sac the vessels draining the remaining abdominal and pelvic viscera. The Fig. 167. — Diagram of the Posterior Portion of the Body of a Human Embryo of 23 mm., showing the Relations of the Retroperitoneal Lymph Sac and the Cisterna Chyli to the Veins. Am, Superior mesenteric artery; Ao, aorta; Cc, cisterna chyli; /5^, retroperitoneal lymph sac; S, suprarenal body; Va, vena azygos; Vci, vena cava inferior; vh, first lumbar vertebra; vsu first sacral vertebra. — (After Sabin.) thoracic duct is formed by the union of two originally distinct portions, one, a downward growth from the left jugular sac and the other a network formed from outgrowths from the retroperi- toneal sac. This network lies behind the aorta and gives rise to the cisterna chyli and the greater portion of the thoracic duct, the frequent duplication of this structure, especially in its| lower por- tion, being thus readily understood from its mode of development. DEVELOPMENT OF THE LYMPHATIC SYSTEM 273 According to this view the endothelium lining the lymphatic vessels is derived directly from that lining the blood-vessels and- the development of the peripheral lymphatics is by a centrifugal growth from the lymph sacs. According to the opposing view (Huntington, McClure) the lymphatics in their initial stage are independent of the blood-vessels, appearing as a number of inter- cellular clefts in the mesenchyme along the line of venous trunks. These clefts become lined by an endo- thelium, blood corpuscles from adjacent blood-islands make their way into them and gradually the clefts unite together to form a capillary network which makes connections with the neighboring vein. In this way are formed the pri- mary networks from which the lymph sacs develop, and the same process leads to the formation of the thoracic duct and the peripheral lymphatics, the duct, for example, arising by the union of a series of clefts in the mesenchyme along the line of the left posterior cardinal vein, the canal so formed eventually uniting with the left jugular lymph sac. On this view the primary lymphatic net- works serve to convey to the main venous trunks the blood which is being formed in isolated blood-islands through- out the mesenchyme, and it is only secondarily, on the cessation of the haematopoietic function of the mesenchyme, that they take on the lymphatic function. Their endothelium arises quite inde- pendently of that of the blood-vascular system and the mode of growth of the vessels is, in a sense, centripetal toward the lymph sacs. Lymph nodes have not been observed in human embryos until toward the end of the third month of development, but they appear in pig embryos of 3 cm. Their unit of structure is a Fig. 168. — Diagram of a Primary Lymph Node of an Embryo Pig of 8 cm. a. Artery; aid, afferent lymph duct; eld, efferent lymph duct; /, follicle. — iSahin.) 18 274 DEVELOPMENT OF THE LYMPHATIC SYSTEM blood-vessel, breaking up at its termination into a leash of capil- laries, around which a condensation of lymphocytes occurs in the mesenchyme. A structure of this kind forms what is termed a lymphoid follicle and may exist, even in this simple condition, in the adult. More frequently, however, there are associated with the follicle lymphatic vessels, or rather the follicle develops in a network of lymphatic vessels, which become an investment of the Fig. 169. — Developing H^molymph Node. be, central blood-vessel; hh, blood-vessel at hilus; ps, peripheral blood sinus. from Morris' Human Anatomy.) -(Siibin follicle and form with it a simple lymph node (Fig. 168). This condition is, however, in many cases but transitory, the artery branching and collections of lymphoid tissue forming around each of the branches, so that a series of follicles is formed, which, together with the surrounding lymphatic vessels, becomes enclosed by a connective- tissue capsule to form a compound lymph node. Later trabeculae of connective tissue extend from the capsule DEVELOPMENT OF THE SPLEEN 275 toward the center of the node, between the folHcles, the lymphatic network gives rise to peripheral and central lymph sinuses, and- the follicles, each with its arterial branch, constitute the peripheral nodules and the medullary cords, the portions of these immediately surrounding the leash of capillaries into which the artery dissolves, constituting the so-called germ centers in which multiplication of the lymphocytes occurs. In various portions of the body, but especially along the root of the mesentery, what are termed hcemolymph nodes occur. In these the lymph sinus is replaced by a blood sinus, but with this ex- ception their structure resembles that of an ordinary lymph node, a simple one consisting of a follicle, composed of adenoid tissue with a central blood-vessel, and a peripheral blood sinus (Fig. 169). The Development of the Spleen.— Recent studies (Mall) have shown that the spleen may well be regarded as possessing a struc- ture comparable to that of the lymph nodes, the pulp being more or less distinctly divided by trabeculae into areas termed pulp cords, the axis of each of which is occupied by a twig of the splenic artery, while the Malpighian corpuscles may be regarded as lymph follicles. The spleen, therefore, seems to fall into the same category of or- gans as the lymph and haemolymph nodes, differing from these chiefly in the absence of sinuses. It has generally been regarded as a development of the mesenchyme situated between the two layers of the mesogastrium. To this view, however, recent ob- servers have taken exception, holding that the ultimate origin of the organ is in part or entirely from the coelomic epithelium of the left layer of the mesogastrium. The first indication of the spleen has been observed in embryos of the fifth week as a sHght elevation on the left (dorsal) surface of the mesogastrium, due to a local thickening and vascularization of the mesenchyme, accompanied by a thickening of the coelomic epithelium which covers the ele- vation. The mesenchyme thickening presents no differences from the neighboring mesenchyme, but the epithelium is not distinctly separated from it over its entire surface, as it is elsewhere in the mesentery. In later stages, which have been observed in detail 276 DEVELOPMENT OF THE SPLEEN in pig and other amnio te embryos, cells separate from the deeper layers of the epithelium (Fig. 1 70) and pass into the mesenchyme thickening, whose tissue soon assumes a different appearance from the surrounding mesenchyme by its cells being much crowded. This migration soon ceases, however, and in embryos of forty- two days the coelomic epitheHum covering the thickening is ^reduced to a simple layer of cells. The later stages of development consist of an enlargement of the thickening and its gradual constriction from the surface of the W Fig. 170. — Section through the Left Layer of the Mesogastrium of a Chick Embryo of Ninety-three Hours, Showing the Origin of the Spleen, ep, Coelomic epithelium; ms, mesenchyme. — (Tonkoff.) mesogastrium, until it is finally united to it only by a narrow band through which the large splenic vessels gain access to the organ. The cells differentiate themselves into trabeculae and pulp cords special collections of lymphoid cells around the branches of the splenic artery forming the Malphigian corpuscles. It has already been pointed out (p. 227) that during embryonic life the spleen is an important haematopoietic organ, both red and white corpuscles undergoing active formation within its substance. The Malpighian corpuscles are collections of lymphocytes in which multipli- cation takes place, and while nothing is as yet known as to the fate of the cells which are contributed to the spleen from the coelomic epithelium, since they quickly come to resemble the mesenchyme cells with which they are associated, yet the growing number of observations indicating an epithelial origin for lymphocytes suggests the possibility that the cells in question may be responsible for the first leukocytes of the spleen. The Coccygeal or Luschka's Ganglion. — In embryos of about 15 cm. there is to be found on the ventral surface of the apex of the LITERATURE 277 coccyx a small oval group of polygonal cells, clearly separated from the surrounding tissue by a mesenchymal capsule. Later- connective- tissue trabecular make their way into the mass, which thus becomes divided into lobules, and, at the same time, a rich vascular supply, derived principally from brandies of the middle sacral artery, penetrates the body, which thus assumes the adult condition in which it presents a general resemblance to a group of lymph follicles. It has generally been supposed that the coccygeal ganglion was in part derived from the sympathetic nervous system and belonged to the same group of organs as the suprarenal bodies. The most recent work on its development (Stoerk) tends, however, to dis- prove this view, and the ganglion seems accordingly to find its place among the lymphoid organs. LITERATURE W. A. Baetjer: *0n the Origin of the Mesenteric Sac and the Thoracic Duct in the Embryo Pig, ' Amer. Journ, Anat., l, 1908. E. VAN Beneden and C. Julin: "Recherches sur la formation des annexes foetales chez les mammiferes," Archiv. de Biolog., v, 1884. A. C. Bernays: " Entwicklungsgeschichte der Atrioventricularklappen," Morphol. Jahrbuch, 11, 1876. G. Born: "Beitrage zur Entwicklungsgeschichte des Saugethierherzens," Archif fiir mikrosk. Anat., xxxiii, 1889. J. L. Bremer: "On the Origin of the Pulmonary Arteries in Mammals," Anat Record, iii, 1909. I. Broman: "Ueber die Entwicklung, Wanderung und Variation der Bauchaorten- zweige bei den Wirbeltiere," Ergeb. Anat. und Entwick.,xvi, 1906. I. Broman: "Ueber die Entwicklung und "Wanderung" der Zweige der aorta ab- dominalis beim Menschen," Anat. Hefte,xxxyi, 1908. E. E. Butterfield: "Ueber die ungranulierte Vorstufen der Myelocyten und ihre Bildung in Milz, Leber und Lymphdriisen," Deutsch. Arch. J. klin. Med., xcii, 1908. E. R. Clark: "Observations on Living Growing Lymphatics in the Tail of the Frog Larva," Anat. Record, in, 1909. C. B. Coulter: "The Early Development of the Aortic Arches of the Cat, with Especial Reference to the Presence of a Fifth Arch," Anat. Record, ni, 1909. Vera Danchakoff: "Origin of the blood cells. Development of the haematopoi- etic organs and regeneration of blood cells from the standpoint of the monophy- letic school," Anat. Rec.,x, 1916. D. M. Davis: "Studies on the chief veins in early pig embryos and the origin of the vena cava inferior," Amer. Journ. Anat., x, 1910. 278 LITERATURE J. Disse: "Die Entstehung des Blutes und der ersten Gefasse im Huhnerei," Archiv fur mikrosk. Anat., xvi, 1879. A. C. F. Eternod: "Premiers stades de la circulation sanguine dans I'ceuf et I'em- bryon humain," Anat. Anzeiger, xv, 1899. H. M. Evans: "On the Development of the Aortae, Cardinal and Umbilical Veins, and the other Blood-vessels of Vertebrate Embryos from Capillaries," Anat. Record, iii, 1909. V. Federow: "Ueber die Entwicklung der Lungenvene," Anat.. Hefte, xl, 1910. W. Felix: "Zur Entwicklungsgeschichte der Rumpfarterien des menschlichen Embryo," Morphol. Jahrh., xli, 1910. G. J. Heuer: "The Development of the Lymphatics in the Small Intestine of the Pig," Amer. Journ. Anat., rx, 1909. W. His: "Anatomic menschlicher Embryonen," Leipzig, 1880-1882. F. Hochstetter: "Ueber die ursprungliche Hauptschlagader der hinteren Glied- masse des Menschen und der Saugethiere, nebst Bemerkungen iiber die Ent- wicklung der Endaste der Aorta abdominalis," Morphol. J ahrbuch,xvi, 1890. F. Hochstetter: "Ueber die Entwicklung der A. vertebralis beim Kaninchen, nebst Bemerkungen iiber die Entstehung der Ansa Vieusseni," Morphol. Jahrhuch, XVI, 1890. F. Hochstetter: "Beitrage zur Entwicklungsgeschichte des Venensystems der Amnioten," Morphol. Jahrhuch, xx, 1893. W. H. Howell: " The Life-history of the Formed Elements of the Blood, Especially the Red Blood-corpuscles," /owm. of Morphol., rv, 1890. W. H. Howell: "Observations on the Occurrence, Structure, and Function of the Giant-cells of the Marrow," Journ. of Morph., iv, 1890. G. S. Huntington: "The Genetic Principles of the Development of the Systemic Lymphatic Vessels in the Mammalian Embryo," Anat. Record, rv, 1910. G. S. Huntington: "The Anatomy and Development of the Systemic Lymphatic Vessels of the Domestic Cat," Memoirs of Wistar Institute, i, 191 2. G. S. Huntington: "The Development of the Mammalian Jugular Lymph Sac, Etc.," Amer. Journ. Anat., xvi, 1914. G. S. Huntington. The Morphology of the Pulmonary Artery in the Mammalia," Anat. Record, vii, 19 19. G. S. Huntington and C. F. W. McClure: "Development of Post-cava and Tribu- taries in the Domestic Cat," Amer. Journ. Anat., vi, 1907. G. S. Huntington and C. F. W. McClure: "The Development of the Main Lymph Channels of the Cat in their Relations to the Venous System," Amer. Journ. Anat., VI, 1907. G. S. Huntington and C. F. W. McClure: "The Anatomy and Development of the Jugular Lymph Sacs in the Domestic Cat," Amer. Journ. Anat., x, 1910. H. E. Jordan: "A Microscopical Study of the Umbilical Vesicle of a 13 mm. Human Embryo, with Special Reference to the Entodermal Tubules and the Blood Islands," Anat. Anzeiger, xxxvii, 1910. O. F. Kampmeier: "The development of the thoracic duct in the pig," Amer. Journ. Anat., XIII, 191 2. C. A. Kling: "Studien uber die Entwicklung der Lymphdriisen beim Menschen," Archiv. fiir mikrosk. Anat., lxiii, 1904. LITERATURE 279 H. Lehmann: "On the Embryonic History of the Aortic Arches in Mammals," Anat. Anzeiger, xxvt, 1905. _ F. T. Lewis: ''The Development of the Vena Cava Inferior," Amer. Journ. of Anat., I, 1902. F. T, Lewis: "The Development of the Veins in the Limbs of Rabbit Embryos," Amer. Journ. Anat., v, 1906. F.T. Lewis: "The Development of the Lymphatic System in Rabbits," Amer. Journ. Anat., V, 1906. F. T. Lewis: "On the Cervical Veins and Lymphatics in Four Human Embryos," Amer. Journ. Anat., rx, 1909. F. T. Lewis: "The First Lymph Glands in Rabbit and Human Embryos," Anat. Record, in, 1909. W. A. Locy: "The Fifth and Sixth Aortic Arches in Chick Embryos, with Comments on the Condition of the same Vessels in other Vertebrates," Anat. Anzeiger xxrx, 1906. F. P. Mall: "Development of the Internal Mammary and Deep Epigastric Arteries in Man," Johns Hopkins Hospital Bulletin, 1898. F. P. Mall: "On the Development of the Blood-vessels of the Brain in the Human Embryo," Amer. Journ. Anat., rv, 1905. F. P. Mall: "On the Development of the Human Heart," Amer. Journ. Anat., XIII, 1912. A. Maximow: " Untersuchungen iiber Blut und Bindegewebe," Arch, fur mikr. Anat., Lxxiii, 1909; lxxiv, 1909; lxxvi, 19 id. C.F.W. McClure: "The Development of the Thoracic and Right Lymphatic Ducts in the Domestic Cat (Felis Domestica)," Anat. Anzeiger, xxxii, 1908. C. F. W. McClure: "The Extra-intimal Theory of the Development of the Mesen- teric Lymphatics in the Domestic Cat," Verhandl. Anat. Gesellsch., xxiv, 1910. C. F. W. McClure: "The Development of the Lymphatic System in the Light of the More Recent Investigations in the Field of Vasculogenesis," Anat. Rec, IX, 1915. C. S. Minot: '^On a Hitherto Unrecognized Form of Blood Circulation without Capillaries in the Organs of Vertebrata," Froc. Boston Soc. Nat. Hist., xxix, 1900. S. Mollier: "Die Blutbildung in der Embryonalen Leber des Menschen und der Saiigetiere," Arch, fur mikrosk. Anat., lxxiv, 1909. C. V. Morill: "On the Development of the Atrial Septum and the Valvular Apparatus in the Right Atrium of the Pig Embryo," Amer. Journ. Anat., xx, 1916. A. G. Pohlman: "The Course of the Blood through the Fetal Mammalian Heart," Anat. Record, 11, 1908. F. Reagan: "The Fifth Aortic Arch of Mammalian Embryos," Amer. Journ. Anat., XII, 1912. F. P. Reagan: "Experimental Studies on the Origin of Vascular Endothelium and of Erythrocytes," Amer. Journ. Anat., xxi, 191 7. E. Retterer: "Sur la part que prend I'epithelium a la formation de la bourse de Fabricius, des amygdales et des plaques de Peyer," Journ. de I' Anat. et de la Physiol., XXIX, 1893. 28o LITERATURE R. Retzer: "Some Results of Recent Investigations on the Mammalian Heart," Anat. Record^ ii, 1908. C. Rose: "Zur Entwicklungsgeschichte des Saugethierherzens," Morphol. Jahrbuch, XV, 1889. Florence R. Sabin: "On the Origin of the Lymphatic System from the Veins and the Development of the Lymph Hearts and Thoracic Duct in the Pig," Amer. Journ. of Anat., i, 1902. Florence R. Sabin: "The Development of the Lymphatic Nodes in the Pig and their Relation to the Lymph Hearts," Amer. Journ. Anat., rv, 1905. Florence R. Sabin: "Further Evidence on the Origin of the Lymphatic Endothe- lium from the Endothelium of the Blood Vascular System," Anat. Record, 11, 1908. Florence R. Sabin: "On the Development of the Lymphatic System in Human Embryos with a Consideration of the Morphology of the System as a Whole/' Amer. Journ. Anat., rx, 1909. Florence R. Sabin: "A Critical Study of the Evidence Presented in Several Recent Articles on the Development of the Lymphatic System," Anat. Record, v, 1911. Florence R. Sabin: "Der Ursprung und die Entwicklung des Lymphgefass- systems," Ergh. Anat. u. Entw., xxi, 1913. Florence R. Sabin: "On the Fate of the Posterior Cardinal Veins, etc., in the Embryo Pig," Carnegie Inst. Puh. Contrih. to EmbryoL, in, 1915. Florence R. Sabin: "Preliminary Note on the Differentiation of Angioblasts and the Method by which they Produce Blood-vessels, Blood plasma and Red Blood-cells as Seen in the Living Chick," Anat. Rec, xiii, 191 7. F. Saxer: "Ueber die Entwicklung und der Bau normaler Lymphdriisen und die Entstehung der roten und weissen BlutkSrperchen," Anat. Hefte, vi, 1896. R. E. ScAMMON AND E. H. NoRRis: "On the Time of the Post-natal Obliteration of the Fetal Blood-passages (Foramen Ovale, Ductus Arteriosus, Ductus Venosus), Anat. Rec. xv, 191 8. H. Schridde: "Die Entstehung der ersten embryonalen Blutzellen des Menschen," Folia hoematol, iv, 1907. H. VON W. Schulte: "Early Stages of Vasculogenesis in the Cat (Felis Domestics), with Especial Reference to the Mesenchymal Origin of Endothelium, Mem. Wistar Inst., No. 3, 1914. H. VON W. Schulte: "The Fusion of the Cardiac Anlages and the Formation of the Cardiac Loop in the Cat (Felis Domestica)," Amer. Journ. Anat., xx, 1916. H. D. Senior: "The Development of the Arteries of the Human Lower Extremity, Amer. Journ. Anal , xxv, 1919. See also Anat. Record, xvii, 1920. H. D. Senior: "An Interpretation of the Recorded Arterial Anomalies of the Human Leg and Foot," Journ. Anat., liii, 1919. L. Stienon: "Sur la Fermature du Canal de Botal," Arch, de Biol., xxvii, 1912. C. R. Stockard: "The Origin of Blood and Vascular Endothelium in Embryos without a Circulation of the Blood and in the .Normal Embryo," Amer. Journ. Anat., xviii, 1915. P. Stohr: "Ueber die Entwicklung der Darmlymphknotchen und uber die Riick- bildung von Darmdriisen." Archiv fiir mikrosk. Anat., li, 1898. LITERATURE 28 1 O. Stoerk: "Ueber die Chromreaktion der Glandula coccygea lind die Beziehung, dieser Driise zum Nervus sympathicus," Arch, fur mikroskop. Anai., Lxrx, 1906. G. L. Streeter: "The Development of the Venous Sinuses of the Dura Mater in the Human Embryo," Amer. Journ. Anat.,xvin, 1915. G. L. Streeter: "The Developmental Alterations in the Vascular System of the Brain of the Human Embryo," Carnegie Inst. Publ. 271, Contrih. to Embryol. No. 24, 1919. O. VAN DER Stricht: "Nouvelles recherches sur la genese des globules rouges et des globules blancs du sang," Archives de Biolog., xii, 1892. O. VAN DER Stricht: " De la premiere origine du sang et des capillaires sanguins dans I'aire vasculaire du Lapin," Comptes Rendus de la Soc. de Biolog. Paris, S6r. 10, II, 1895. J. Tandler: "Zur Entwicklungsgeschichte der Kopfarterien bei den Mammalia," Morphol. Jahrhuch, xxx, 1902. J. Tandler: "Zur Entwickelungsgeschichte der menschlichen Darmarterien," Anat. Hefie, XKiii, igo^. J. Tandler: "Ueber die Varietaten der arteria coeliaca und deren Entwicklung," Anat. Hefte, xxv, 1904. J. Tandler: "Ueber die Entwicklung des fiinften Aortenbogens und der fiinften Schlundtasche beim Menschen," Anat. Hefte, xxxviii, 1909. W. Tonkoff: "Die Entwickelung der Milz bei den Amnioten," Arch. fUr mikrosk. Anat., lvi, 1900. Bertha de Vriese: "Recherches sur revolution des vaissaux sanguins des membres chez I'homme," Archiv de Biolog., xvin, 1902. F. Weidenreich: "Die roten Blutkorperchen," Ergb. Anat. und Entwick., xm, 1903, xrv, 1904. F. Weidenreich: "Die Leucocyten und verwandte Zellformen," Ergeb. Anat. und Entwick., XVI, 191 1. J. H. Wright: "The Histogenesis of the Blood Platelets," Journ. of Morph., xxi, 1910, CHAPTER X THE DEVELOPMENT OF THE DIGESTIVE TRACT AND GLANDS The greatest portion of the digestive tract is formed by the constriction off of the dorsal portion of the yolk-sac, as shown in Fig. 53, the result being the formation of a cylinder, closed at either end and composed of a layer of splanchnic mesoderm lined on its inner surface by endoderm. This cylinder is termed the archen- teron and has connected with it the yolk-stalk and the allantois, the latter communicating with its somewhat dilated terminal portion, which also receives the ducts of the primitive kidneys and is known as the cloaca (Fig. 172). At a very early stage of development the anterior end of the embryo begins to project slightly in front of the yolk-sac, so that a shallow depression is formed between the two structures. As the constriction of the embryo from the sac proceeds, the anterior portion of the brain becomes bent ventrally and the heart makes its appearance immediately in front of the anterior surface of the yolk-sac, and so the depression mentioned above becomes deep- ened (Fig. 171) to form the oral sinus. The floor of this, lined by ectoderm, is immediately opposite the anterior end of the archen- teron, and, since mesoderm does not develop in this region, the ectoderm of the sinus and the endoderm of the archenteron are directly in contact, forming a thin pharyngeal membrane separating the two cavities (Fig. 171, pm). In embryos of 2.15 mm. this membrane is still existent, but soon after it becomes perforated and finally disappears, so that the archenteron and oral sinus become continuous. Toward its posterior end the archenteron comes into somewhat similar relations with the ectoderm, though a marked difference is 282 DEVELOPMENT OF THE DIGESTIVE TRACT 283 noticeable in that the area over which the cloacal endoderm is in contact with the ectoderm to form the cloacal membrane (Figr 172, cm) lies a little in front of the actual end of the archenteric cylinder, the portion of the latter which lies posterior to the mem- brane forming what has been termed the postanal gut {p. an). This diminishes in size during development and early disappears altogether, and the pouch-like fold seen in Fig. 172 between the intestinal portion of the archeiiteron and the allantoic stalk {at) deepening until its floor comes into contact with the cloacal membrane, the cloaca becomes divided into a ventral portion, with which the allantois and the primitive excretory ducts {w) are connected, and a dorsal portion which becomes the lower end of the rectum. This latter abuts upon the dorsal portion of the cloacal membrane, and this eventually ruptures, so that the posterior communi- cation of the archenteron with the exterior becomes estab- lished. This rupture, however, does not occur until a com- paratively late period of development, until after the embryo has reached the fetal stage; nor does the position of the membrane correspond with the adult anus, since later there is a considerable development of mesoderm around the mouth of the cloaca, bulg- ing out, as it were, the surrounding ectoderm, more especially anteriorly where it forms the large genital tubercle (see Chapter XIII), and posteriorly where it produces the anal tubercle. This appears as a rounded elevation on each side of the median line, immediately behind the cloacal membrane and separated from the root. of the caudal projection by a depression, the precaudal recess. Later the two elevations unite across the median line to form a Fig. 171. — Reconstruction of the Anterior Portion of an Embryo of 2.15 MM. ah. Aortic bulb; h, heart; o, auditory capsule; op, optic evagination; pm, pharyngeal membrane. — (His.) \7^ 284 DIGESTIVE TRACT AND GLANDS transverse ridge, the ends of which curve forward and eventually meet in front of the original and orifice. From the mesoderm of the circular elevation thus produced the external sphincter ani muscle is formed, and it would seem that so much of the lower end of the rectum as corresponds to this muscle is formed by the inner surface of the elevation and is therefore ectodermal. The definite anus being at the end of this terminal portion of the gut is there- fore some distance away from the position of the original cloacal membrane. -nc Fig. 172. — Reconstruction of the Hind End of an Embryo 6.5 mm. Long. al, Allantois; &, belly-stalk; cl, cloaca; cm, cloacal membrane; i, intestine; n. spinal cord; nc, notochord; p.an, postanal gut; ur, outgrowth to form; ureter and metanephros; w. Wolffian duct. — (Keibel.) It will be noticed that the digestive tract thus formed consists of three distinct portions, an anterior, short, ectodermal portion, an endodermal portion representing the original archenteron, and a posterior short portion which is also ectodermal. The differen- tiation of the tract into its various regions and the formation of the various organs found in relation with these may now be con- sidered. DEVELOPMENT OF THE MOUTH REGION 285 The Development of the Mouth Region. — The deepening of the oral sinus by the development of the first branchial arch an^ its separation into the oral and nasal cavities by the development of the palate have already been described (p. 102), but, for the sake of continuity in description, the latter process may be briefly recalled. At first the nasal pits communicate with the oral sinus by grooves lying one on each side of the fronto-nasal process, but by the union of the latter, through its processus globulares, with the maxillary processes these communications are interrupted and the floors of the nasal pits are separated from the oral cavity by thin hucco-nasal membranes, formed of the nasal epithelium in contact with that of the oral cavity. In embryos of about 15 mm. these membranes break through and disappear, and the nasal and oral cavities are again in communication, but the communications are now behind the maxillary processes and constitute what are termed the primitive choance. The oral cavity at this stage does not, however, correspond with the adult mouth cavity, since there is as yet no palate, the roof of the oral cavity being the base of the skull. From the maxillopalatine portions of the upper jaw, shelf-like ridges begin to grow, being at first directed downward so that their surfaces are parallel with the sides of the tongue, which projects up between them. Later, however, they become bent upward to a horizontal position (Fig. 173) and eventually meet in the median line to form the palate, separating the nasal cavities from the mouth cavity. All that portion of the original oral cavity which Hes behind the posterior edge of the palatal shelf is now known as the pharynx, the boundary between this and the mouth cavity being emphasized by the prolongation backward and downward of the posterior angles of the palatal shelf as ridges, which form the pharyngo-palatine arches (posterior pillars of the fauces) . The nasal cavities now communicate with the upper part of the pharynx (naso-pharynx) by the posterior choanae. The palatal processes are entirely derived from the maxillary processes, the premaxillary portion of the upper jaw which is a derivative of the fronto-nasal process, not taking part in their formation. Consequently a gap exists between the palatal 286 DEVELOPMENT OF THE MOUTH REGION shelves and the premaxillae for a time, by which the nasal and mouth cavities communicate; it places the organ of Jacobson (see p. 434) in communication with the mouth cavity and may persist until after birth. Later it becomes closed over by mucous membrane, but may be recognized in the dried skull as the fora- men incisivum (anterior palatine canal). Occasionally there is a failure of the union of the palatal plates, the condition known as cleft palate resulting. The inhibition of develop- ment which brings about this condition may take place at different stages, but frequently it occurs while the plates still have an almost vertical direction. Typically cleft palate is a deficiency in the median Fig. 173. — View of iiu: Roof of the Oral Fossa of Embryo showing the Lip- Groove AND the Formation of the Palate. — {His.) line of the roof of the mouth, not affecting the upper jaw, but very frequently it is combined with the defect which produced hare-lip (see p. 98), in which case the cleft may be continued through the upper jaw between its maxillary and premaxillary portions on either or both sides, according to the extent of the defect. At about the fifth week of development a downgrowth of epi- thelium into the substance of both the maxillary and fronto-nasal processes above and the mandibular process below takes place, and the surface of the downgrowth becomes marked by a deepen- ing groove (Fig. 173), which separates an anterior fold, the lip, from the jaw proper (Fig. 174). Mention should also be made of the fact that at an early stage of development a pouch is formed in the median line of the roof of the oral sinus, just in front of the pharyngeal membrane, by an outgrowth of the epithelium. This DEVELOPMENT OF THE TEETH 287 pouch, known as Rathke^s pouch, comes in contact above with a downgrowth from the floor of the brain and forms with it the- pituitary body (see p. 403). The Development of the Teeth. — When the epithelial down- growth which gives rise to the lip groove is formed, a horizontal outgrowth develops from it which extends backward into the sub- stance of the jaw, forming what is termed the dental shelf (Fig. 174 A). This at first is situated on the anterior surface of the jaw, but with the continued development of the lip fold it is gradually shifted until it comes to lie upon the free surface (Fig. 174,5), where its superficial edge is marked by a distinct groove, the dental groove (Fig. 173). At first the dental shelf of each jaw is a con- tinuous plate of cells, uniform in thickness throughout its entire width, but later ten thickenings develop upon its deep edge, and beneath each of these the mesoderm condenses to form a dental papilla, over the surface of which the thickening moulds itself to form a cap, termed the enamel organ (Fig. 174, B). These ten papillae in each jaw, with their enamel caps, represent the teeth of the first dentition. The papillae do not, however, project into the very edge of the dental shelf, but obliquely into what, in the lower jaw, was origi- nally its under surface (Fig. 174, B), so that the edge of the shelf is free to grow still deeper into the substance of the jaw. This it does, and upon the extension so formed there is developed in each jaw a second set of thickenings, beneath each of which a dental papilla again appears. These tooth-germs represent the incisors canines, and premolars of the permanent dentition. The lateral edges of the dental shelf being continued outward toward the arti- culations of the jaws as prolongations which are not connected with the surface epithelium, opportunity is afforded for the develop- ment of three additional thickenings on each side in each jaw, and, papillae developing beneath these, twelve additional tooth-germs are formed. These represent the permanent molars; their forma- tion is much later than that of the other teeth, the germ of ^the second molar not appearing until about the sixth week after birth, while that of the third is delayed until about the fifth year. 288 DEVELOPMENT OF THE TEETH As the tooth-germs increase in size, they approach nearer and nearer to the surface of the jaw, and at the same time the enamel organs separate from the dental shelf until their connection with it is a mere neck of epithelial cells. In the meantime the dental shelf itself has been undergoing degeneration and is reduced to a reticulum which eventually completely disappears, though frag- ments of it may occasionally persist and give rise to various mal- formations. With the disappearance of the last remains of the Fig. 174. — Transverse Sections through the Lower Jaw showing the Formation of the Dental Shelf in Embryos of (A) 17 mm. and (J3) 40 mm. — {Rose.) shelf, the various tooth-germs naturally lose all connection with one another. It will be seen, from what has been said, that each tooth-germ consists of two portions, one of which, the enamel organ, is de- rived from the ectoderm, while the other, the dental papilla, is mesenchymatous. Each of these gives rise to a definite portion of the fully formed tooth, the enamel organ, as its name indicates, DEVELOPMENT OF THE TEETH 289 producing the enamel, while from the dental papilla the dentine and pulp are formed. — The cells of the enamel organ which are in contact with the sur- face of the papilla, at an early stage assume a cylindrical form and od. Fig. 175. — Section through the First Molar Tooth of a Rat, Twelve Days Old. Ap, Periosteum; R, dentine; Rp, epidermis; Od, odontoblasts; S, enamel; SRa and SRi, outer and inner layers of the enamel organ; SR, portion of the enamel organ which does not produce enamel, — {von Brunn.) become arranged in a definite layer, the enamel membrane (Fig. 175, SEi), while the remaining cells (SEa) apparently degenerate eventually, though they persist for a time to form what has been termed the enamel pulp. The formation of the enamel seems to be 19 290 DEVELOPMENT OF THE TEETH due to the direct transformation of the enamel cells, the process be- ginning at the basal portion of each cell, and as a result, the enamel consists of a series of prisms, each of which represents one of the cells of the enamel membrane. The transformation proceeds until the cells have become completely converted into enamel prisms, except at their very tips, which form a thin membrane, the enamel cuticle, which is shed soon after the eruption of the teeth. The dental papillae are at first composed of a closely packed mass of mesenchyme cells, which later become differentiated into connective tissue into which blood-vessels and nerves penetrate. The superficial cells form a more or less definite layer (Fig. 175,0^), and are termed odontoblasts, having the function of manufacturing the dentine. This they accomplish in the same manner as that in which the periosteal osteoblasts produce bone, depositing the den- tine between their surfaces and the adjacent surface of the enamel. The outer surface of each odontoblast is drawn out into a number of exceedingly fine processes which extend into the dentine to oc- cupy the minute dentinal tubules, just as processes of the osteo- blasts occupy the canaHculi of bone. At an early stage the enamel membrane forms an almost com- plete investment for the dental papilla (Fig. 175), but as the ossifi- cation of the tooth proceeds, it recedes from the lower part, until finally it is confined entirely to the crown. The dentine forming the roots of the tooth then becomes enclosed in a layer of cement, which is true bone and serves to unite the tooth firmly to the walls of its socket. As the tooth increases in size, its extremity is brought nearer to the surface of the gum and eventually breaks through, the eruption of the first teeth usually taking place during the last half of the first year after birth. The growth of the per- manent teeth proceeds slowly at first, but later it becomes more rapid and produces pressure upon the roots of the primary teeth. These roots then undergo partial absorption, and the teeth are thus loosened in their sockets and are readily pushed out by the further growth of the permanent teeth. The dates and order of the eruption of the teeth are subject to con- siderable variation, but the usual sequence is somewhat as follows: DEVELOPMENT OF THE TONGUE 29 T - Primary Dentition. Median incisors 6th to 8th month. Lateral incisors 8th to 12th month. First molars Beginning of 2d year. Canines 1 3'^ years. Second molars 3 to 3 3^ years. Permanent Dentition First molars 7th year. Middle incisors 8th year. Lateral incisors gth year. First premolars loth year. Second premolars nth year. Canines 1 4.1, 4. 4.u Second molars I 13th to 14* years. Third molars 1 7th to 40th years. In a considerable percentage of individuals the third molars (wisdom teeth) never break through the gums, and frequently when they do so they fail to reach the level of the other teeth, and so are only partly functional. These and other peculiarities of a structural nature shown by these teeth indicate that they are undergoing a retrogressive evolution. The Development of the Tongue. — Strictly speaking, the tongue is largely a development of the pharyngeal region of the digestive tract and only secondarily grows forward into the floor of the mouth. In embryos of about 3 mm. there may be seen in the median line of the floor of the mouth, between the ventral ends of the first and second branchial arches, a small rounded elevation which has been termed the tuherculum impar (Fig. 176, Ti). It was at one time believed that this gave rise to the anterior portion of the tongue, but recent observations seem to show that it reaches its greatest development in embryos of about 8 mm., after which it becomes less prominent and finally unrecognizable. But before this occurs a swelling appears in the anterior part of the mouth on each side of the median line (Fig. 176, /), and these gradually increase in size and eventually unite in the median line to form the main mass of the body of the tongue. They are separated from the neighboring portions of the first branchial arch by a deep groove, the alveolo-lingual groove, and posteriorly are separated 292 DEVELOPMENT OF THE TONGUE from the second arch by a groove which later becomes distinctly V-shaped (Fig. 177), a deep depression, which gives rise to the r< i -Cop Fig. 176. — Floor of the Mouth and Pharynx of an Embryo of 7.5 mm., from A Reconstruction. Cop. Copula; /, furcula; t, swelling that gives rise to the body of the tongue; Ti, tuberculum impar; I-III, branchial arches, thyreoid body, lying at the apex of the V. Behind the thyreoid pouch .the ventral ends of the second and third branchial arches unite to form an elevation, the copula (Fig. 176, Cop), and from ^^ / ^[^fcfer^f this and the adjacent portions of the second and third arches the posterior portion of the tongue develops. The tongue then consists of two distinct portions, which eventually fuse together, but the groove which Fig. 177.— The Floor of the originally separated them remains Pharynx of an Embryo of about j^ore or less clearly distinguishable 20 MM. -^ *=» «^, Epiglottis; /c, foramen caecum; t^ and f 2 median and lateral portions of the tongue. — {His.) f( (Fig. 177), the vallate papillae (see p. 435) developing immediately an- terior to it. The tongue is essentially a muscular .organ, being formed of a central mass of muscular tissue, enclosed at the sides and dorsally by mucous membrane derived from the floor of the mouth and pharynx. THE SALIVARY GLANDS 293 The muscular tissue consists partly of fibers limited to the substance of the tongue and forming the m. lingualis, and also of a number of ex- trinsic muscles, the hyoglossi, genioglossi, styloglossi, glossopalatini and chondroglossi. The last two muscles are innervated by the vagus nerve, and the remaining extrinsic muscles receive fibers from the hypoglossal, while the lingualis is supplied partly by the hypoglossal and partly, apparently, by the facial through the chorda tympani. That the facial should take part in the supply is what might be ex- pected from the mode of development of the tongue, but the hypo- glossal has been seen to correspond to certain primarily postcranial metameres (p. 172), and its relation to structures taking part in the formation of an organ belonging to the anterior part of the pharynx seems somewhat anomalous. It may be supposed that in the evolu- tion of the tongue the extrinsic muscles, together with a certain amount of the lingualis, have grown into the tongue thickenings from regions situated much further back, for the most part from behind the last branchial arch. Such an invasion of the tongue by muscles from posterior segments would explain the distribution of its sensory nerves (Fig. 178). The anterior portion, from its position, would naturally be supplied by branches from the fifth and seventh nerves, while the posterior portion might be expected to be supplied by the seventh. There seems, how- ever, to have been a dislocation forward, if it may be so expressed, of the mucous membrane, the sensory distribution of the ninth nerve extend- ing forward upon the posterior part of the anterior portion of the tongue, while a considerable amount of the posterior portion is supplied by the tenth nerve. The distribution of the sensory fibers of the facial is probably confined entirely to the anterior portion, though further in- formation is needed to determine the exact distribution of both the motor and sensory fibers of this nerve in the tongue. The Development of the Salivary Glands. — In en^bryos of about 8 mra. a slight furrow may be observed in the floor of the groove which connects the lip grooves of the upper and lower jaws at the angle of the mouth and may be known as the cheek groove. In later stages this furrow deepens and eventually becomes closed in to form a hollow tubular structure, which in embryos of 17 mm. has separated from the epithelium of the floor of .the cheek groove except at its anterior end and has become embedded in the con- nective tissue of the cheek. This tube is readily recognizable as the parotid gland and duct, and from the latter as it passes across the masseter muscle a pouch-like outgrowth is early formed which probably represents the socia parotidis. 294 THE SALIVARY GLANDS The submaxillary gland and duct appear in embryos of about 13 mm. as a longitudinal ridge-like thickening of the epithelium of the floor of the alveolo-lingual groove (see p. 291). This ridge gradually separates from behind forward from the floor of the groove and sinks into the subjacent connective tissue, retaining, however, its connection with the epithelium at its anterior end. Fig. 1 78. — Diagram of the Distribution of the Sensory nerves of the Tongue. The area supplied by the fifth (and seventh) nerve is indicated by the transverse lines; that of the ninth by the oblique lines; and that of the tenth by the small circles. — (Zander.) which indicates the position of the opening of the duct. In the vicinity of this there appear in embryos of 24.4 mm. five small bud-like downgrowths of the epithelium (Fig. 179, SL), which later increase considerably in number as well as in size, and constitute a THE SALIVARY GLANDS 295 group of glands which are generally spoken of as the sublingual gland. As these representatives of the various glands increase in length, they become lobed at their deeper ends, and the lobes later give rise to secondary outgrowths which branch repeatedly, the terminal branches becoming the alveoli of the glands. A lumen early appears in the duct portions of the structures, the alveoli remaining solid for a longer time, although they eventually also become hollow. j:ai Mart. Pig. 179. — Transverse Section of the Lower Jaw and Tongue of an Embryo of about 20 mm. D, Digastric muscle; GGl., genioglossus, GH.\ geniohyoid; I.Al, inferior alveolar nerve; Man, mandible; MK. Meckel's cartilage; My, mylohyoid; SL, sublingual gland; S.Mx, submaxillary duct; T, tongue. It is to be noted that each parotid and submaxillary consists of a single primary outgrowth, and is therefore a single structure and not a union of a number of originally separate parts. The sublingual glands of adult anatomy are usually described as opening upon the floor of the mouth by a number of separate ducts. This arises from the fact that the majority of the glands which form in the vicinity of the opening of Wharton's duct remain quite small, only one of them on each side giving rise to the sublingual gland proper. The small glands have been termed the alveolo-lingual glands, and each one of them is equivalent to a parotid or submaxillary gland. In other words, there are in reality not three pairs of salivary glands, but from fourteen to sixteen pairs, there being usually from eleven to thirteen alveolo-lingual glands on each side. 296 THE PHARYNX The Development of the Pharynx. — The pharynx represents the most anterior part of the archenteron, that portion in which the branchial arches develop, and in the embryo it is relatively much longer than in the adult, the diminution being brought abou t by the folding in of the posterior arches and the formation of the sinus praecervicahs already described (p. 100). Between the vari- ous branchial arches, grooves occur, representing the endodermal portions of the grooves which separate the arches. During devel- opment the first of these becomes converted into the tympanic cavity of the ear and the Eustachian tube (see Chapter XV) ; the second disappears in its upper part, the lower persisting as the fossa in which the tonsil is situated; while the lower parts of the remaining two are represented by the sinus piriformis of the larynx (His), and also leave traces of their existence in detached portions of their epithelium which form what are termed the branchial epithelial bodies, and take part in the formation of the thyreoid and thymus glands. In the floor of the pharynx behind the thickenings which pro- duce the tongue there is to be found in early stages a pair of thick- enings passing horizontally backward and uniting in front so that they resemble an inverted U (Fig. 180, /). These ridges, which form what is termed thefurcula (His), are concerned in the forma- tion of parts of the larynx (see p. 357). In the part of the roof of the pharynx which comes to lie between the openings of the Eusta- chian tubes, a collection of lymphatic tissue takes place beneath the mucous membrane, forming the pharyngeal tonsil, and imme- diately behind this there is formed in the median line an upwardly projecting pouch, the pharyngeal bursa, first certainly noticeable in embryos 6.5 mm. in length. This bursa has very generally been regarded as the persistent re- mains of Rathke's pouch (p. 287), especially since it is much more pronounced in fetal than in adult life. It has been shown, however, that it is formed quite independently of and posterior to the true Rathke's pouch (Killian), and Huber's observations show that in man it represents a region of the pharyngeal epithelium with which the noto- chord retains connection after it has elsewhere separated from the endo- derm. The epithelium becomes thickened at the point of contact with THE BRAJTCHIAL EPITHELIAL BODIES 297 the notochord and is later drawn out into a pouch or bursa, which usually disappears after birth, but may result in the formation of a cyst in the roof of the pharynx. Structures that have been identified witlT the pharyngeal bursa in the embryos of other mammals, such as the pig, are, however, formed independently of any contact of the notochord with the pharyngeal epithelium. The tonsils are formed from the epithelium of the second bran- chial groove. At about the fourth month solid buds begin to grow from the epithelium into the subjacent mesenchyme, and depressions appear on the surface of this region. Later the buds become hollow by a cornification of their central cells, and open upon the floor of the depressions which represent the crypts of the tonsil. In the meantime lymphocytes, concerning whose origin there is a difference of opinion, collect in the subjacent mesenchyme and eventually aggregate to form lymphatic folli- cles in close relation with the buds. Whether the lymphocytes wander out from the blood into the mesenchyme or are derived directly from the epithelium or the mes- enchyme cells is the question at issue. The tonsil may grow to a size sufficient to fill up completely the groove in which it forms, but not infrequently a marked depression, the fossa supratonsillaris, ex- ists above it and represents a portion of the original second branchial furrow. The groove of Rosenmuller, which was at one time thought to be also a remnant of the second furrow, is a secondary de- fig. i so.— The Floor pression which appears in embryos of 11.5 ZJZ o^a'^rMM."' '" cm. behind the opening of the Eustachian f^ Furcuia; /. tubercuium tube, in about the region of the third impar— (His.) branchial furrow. The Development of the Branchial Epithelial Bodies. — These are structures which arise either as thickenings or as outpouchings of the epithelium lining the lower portions of the inner branchial furrows. Five pairs of these structures are developed and, in addition, there is a single unpaired median body. This last makes 298 THE BRANCHIAL EPITHELIAL BODIES its appearance in embryos of about- 3 mm., and gives rise to the major portion of the thyreoid body. It is situated immediately behind the anterior portion of the tongue, at the apex of the groove between this and the posterior portion, and is first a sUght pouch- like depression. As it deepens, its extremity becomes bilobed, and after the embryo has reached a length of 7 mm. it becomes com- pletely separated from the floor of the pharynx. The point of its original origin is, however, permanently marked by a circular depression, the foramen ccecum (Fig. 177, /c). Later the bilobed body migrates down the neck and becomes a solid transversely elongated mass (Fig. 181, th), into the substance of which tra- FiG. 181. — Reconstructions of the Branchial Epithelial Bodies of Embryos. OF (A) 14 MM. AND (B) 26 MM. ao. Aorta; Ith, lateral thyreoid; ph, pharynx; pth^ and pth^, parathyreoids; //?, thyreoid; thy, thymus; vc, vena cava superior. — (Tourneux and Verdun.) beculae of connective tissue extend, dividing it into a network of anastomosing cords which later divide transversely to form follicles. When the embryo has reached a length of 2.6 cm., a cylindrical outgrowth arises from the anterior surface of the mass, usually a Httle to the left of the median line, and extends up the neck a varying distance, forming, when it persists until adult life, the so-called pyramid of the thyreoid body. This account of the pyramid follows the statements made by recent workers on the question (Tourneux and Verdun); His has claimed that it is the remains of the stalk connecting the thyreoid with the floor of the pharynx, and which he terms the thyreo-glossal duct. Two other pairs of bodies enter into the intimate relations with THE BRANCHIAL EPITHELIAL BODIES 299 pthmlV ihmlV pthm III the thyreoid, forming what have been termed the parathyreoid bodies (Fig. 181, pth^ and pth"^). One of these pairs arises as^ thickening of the dorsal portion of the fourth branchial groove and the other comes from the corresponding portion of the third groove. The members of the former pair, after separating from their points of origin, come to lie on the dorsal surface of the lateral portions of the thyreoid body (Fig. 182, pthm IV) in close proximity to the lateral thy- reoids, while those of the other pair, passing further back- ward, come to rest behind the lower border of the thyreoid (Fig. 182, pthm III). The cells of these bodies do not become divided into cords by the ingrowth of connective tissue to the same extent as those of the thyreoids, nor do they become separated into follicles, so that the bodies are readily distinguishable by their structure from the thyreoid. From the ventral portion of the third branchial groove a pair of evaginations de- velop, similar to those which produce the lateral thyreoids. These elongate greatly, and growing downward ventrally to the thyreoid and separating from their points of origin, come to lie below the thyreoids, forming the thymus gland (Fig. 181, thy). As development proceeds they pass further backward and come eventually to rest upon the anterior surface of the pericardium. The cavity which they at first contain is early thmlli Fig. 182. — Thyreoid, Thymus and Epi- thelial Bodies of a New-born Child. pthm III and pthm IV, Parathyreoids ; sd, thyreoid; thm III, thymus; thm IV, lateral thyreoid. — (Groschuff.) 300 THE BRANCHIAL EPITHELIAL BODIES obliterated and the glands assume a lobed appearance and become traversed by trabeculae of connective tissue. Lymphocytes, de- rived, according to some recent observations, directly from the epithelium of the glands, make their appearance and gradually increase in number until the original epithelial cells are represented only by a number of peculiar spherical structures, consisting of cells arranged in concentric layers and known as HassaWs cor- puscles. Pig. 183. — Diagram showing the Origin of the Various Branchial Epithelial Bodies. Ith, Lateral thyreoids; pp, ultimobranchial bodies; pht^ and phi^, pjarathyreoids; //j, median thyreoid; thy, thymus; I to IV, branchial grooves. — (Kohn.) The glands increase in size until about the fifteenth year, after which they gradually undergo degeneration into a mass of fibrous and adipose tissue. A pair of evaginations very similar to those that give rise to the thymus are also formed from the ventral portion of the fourth branchial groove (Figs. 181, ^ and 183, Ith). As a rule they com- pletely disappear in later stages of development, but occasionally they undergo differentiation into small masses of thymus-like tissue, which remain associated with the parathyreoids from the THE CESOPHAGUS 3OI same arch (Fig. 182, thm IV). They have been termed lateral thyreoids, but the term is a misnomer, since they take no essential part in the formation of the thyreoid body. Finally, a pair of outgrowths arise from the floor of the pharynx just behind the fifth branchial arch, in the region where the fifth groove, if developed, would occur. These ultimo-branchial bodies, as they have been called, usually undergo degeneration at an early stage and disappear completely, though occasionally they persist as cystic structures embedded in the substance of the thyreoid. The relation of these various structures to the branchial grooves is shown by the annexed diagram (Fig. 183), and from it, it will be seen that the bodies derived from the third and fourth grooves are serially equivalent. Comparative embryology makes this fact still more evident, since, in the lower vertebrates, each branchial groove contrib- utes to the formation of the thymus gland. The terminology used above for the various bodies is that generally applied to the mammalian organs, but it would be better, for the sake of comparison with other vertebrates, to adopt the nomenclature proposed by Groschuff, who terms each lateral thyreoid a thymus IV, while each thymus lobe is a thymus III. Similarly the para thyreoids are termed para thymus and III and IV, the term thyreoid being limited to the median thryeoid. The Musculature of the Pharynx. — The pharynx differs frohi other portions of the archenteron in the fact that its walls are fur- nished with voluntary muscles, the principal of which are the con- strictors and the stylo-pharyngeus. This pecuHarity arises from the relations of the pharynx to the branchial arches. It has been seen that in the higher mammalia the dorsal ends of the third, fourth, and fifth branchial cartilages disappear; the muscles origi- nally associated with these structures persist, however, and give rise to the muscles of the pharynx, which consequently are innervated by the ninth and tenth nerves. The Development of the (Esophagus.— ^From the ventral side of the lower portion of the pharynx an evagination develops at an early stage, which is destined to give rise to the organs of respi- ration; the development of this may, however, be conveniently postponed to a later chapter (Chapter XII). The oesophagus is at first a very short portion of the archen- teron (Fig. 184, A), but as the heart and diaphragm recede into 302 THE STOMACH the thorax, it elongates (Fig. 184, B) until it eventually forms a considerable portion of the digestive tract. Its endodermal lining like that of the rest of the digestive tract except the pharynx, is surrounded by splanchnic mesoderm whose cells become converted into non-striated muscular tissue, which, by the fourth month, has separated into an inner circular and an outer longitudinal layer. The Development of the Stomach and Intestines. — By the time the embryo has reached a length of about 5 mm. its constric- FiG. 184. — Reconstruction of the Digestive Tract of Embryos of (A) 4.2 mm. AND (B) 5 MM. all, Allantois; cl, cloaca; I, lung; It, liver; Rp, Rathke's pouch; S, stomach; /, tongue; th, thyreoid body; Wd, Wolffian duct; y, yolk-stalk. — (His.) tion from the yolk-sac has proceeded so far that a portion of the digestive tract anterior to the yolk-sac can be recognized as the stomach and a portion posterior as the intestine. As first the stomach is a simple, spindle-shaped enlargement (Fig. 184) and the intestine a tube without any coils or bends, but since in later THE INTESTINE 3O3 stages the digestive tract grows much more rapidly in length than the abdominal cavity, a coiling of the intestine becomes necessary. The elongation of the stomach early produces changes in its position, its lower end bending over toward the right, while its up- per end, owing to the development of the liver, is forced somewhat toward the left. At the same time the entire organ undergoes a rotation about its longitudinal axis through nearly ninety degrees, so that, as the result of the combination of these two changes, what was originally its ventral border becomes its lesser curvature and what was originally its left surface becomes its ventral surface. Hence it is that the left vagus nerve passes over the ventral and the right over the dorsal surface of the stomach in the adult. Fig. 185. — The Gastric Epithelium from an Embryo of 10 mm. From a Re- construction. D.ch, Common bile duct; D.p.d, duct of dorsal pancreas; I.ang, angular notch be- tween cardiac and pyloric portions; Oe, oesophagus. — (F. T. Lewis.) In the meantime the elongation of the oesophagus has carried the stomach further away from the lower end of the pharynx, *and from being spindle-shaped it has become more pyriform, the fundus having appeared as an outpouching of the wall. At first the py- loric portion is almost half the length of the entire organ (Fig. 185), but later it becomes relatively shorter and the region of the pylorus becomes marked as a slight dilation. It is worthy of note that two folds of mucous membrane are early to be seen extending from the opening of the oesophagus along the lesser curvature to the com- mencement of the pyloric portion. They form the walls of a 304 THE INTESTINE groove (Fig. 185), which may be recognized in the adult stomach and to which the term gastric canal has been apphed (F. T. Lewis) . The growth of the intestine results in its being thrown into a loop opposite the point where the yolk-stalk is still connected with it, the loop projecting ventrally into the portioA of the coelomic cavity which is contained within the umbilical cord, and being placed so that its upper Hmb lies to the right of the lower one. Up- on the latter a slight pouch-like lateral outgrowth appears which Pig. 186. — Reconstruction of Embryo of 20 mm. C, Caecum; K, kidney; L, liver; S, stomach; SC, suprarenal bodies; W, mesonephros. (Mall.) is the beginning of the ccBcum and marks the line of union of the future small and large intestine. The small intestine, continuing to lengthen more rapidly than the large, assumes a sinuous course (Fig. 186), in which it is possible to recognize six primary coils which continue to be recognizable until advanced stages of develop- ment and even in the adult (Mall). The first of these is at first indistinguishable from the pyloric portion of the stomach and can THE INTESTINE 305 be recognized as the duodenum only by the fact that it has con- nected with it the ducts of the Hver and pancreas; as development proceeds, however, its caliber diminishes and it assumes the ap- pearance of a portion of the intestine. The remaining coils elongate rapidly and are thrown into numerous secondary coils, all of which are still contained within the coelom of the umbilical cord (Fig. 187) . When the embryo has reached a length of about 40 mm. the coils rather suddenly return to the abdominal cavity, and now the caecum is thrown over to- ward the right, so that it comes to lie immediately beneath the Fig. 187. — Reconstruction of the Intestine of an Embryo of 19 mm. The Figures on the Intestine Indicate the Primary Coils. — (Mall.) liver on the right side of the abdominal cavity, a position which it retains until about the fourth month after birth (Treves). The portion of the large intestine which formerly projected into the umbihcal coelom now lies transversely across the upper part of the abdomen, crossing in front of the duodenum and having the re- maining portion of the small intestine below it. The elongation continuing, the secondary coils of the small intestine become more numerous and the lower portion of the large intestine is thrown into a loop which extends transversely across the lower part of the abdominal cavity and represents the sigmoid flexure of the colon . At the time of birth this portion of the large intestine is relatively 20 3o6 THE INTESTINE much longer than in the adult, amounting to nearly half the entire length of the colon (Treves), but after the fourth month after birth a readjustment of the relative lengths of the parts of the colon occurs, the sigmoid flexure becoming shorter and the rest of the colon proportionally longer, whereby the caecum is pushed Fig. 1 88. — Representation of the Coilings of the Intestine in the Adult Condition. The Numbers indicate the Primary Coils, — (Mall.) downward until it lies in the right iliac fossa, the ascending colon being thus established.. When this condition has been reached, the duodenum, after passing downward for a short distance so as to pass dorsally to the transverse colon, bends toward the left and the secondary coils derived from the second and third primary coils come to occupy THE INTESTINE 307 the left upper portion of the abdominal cavity. Those from the fourth primary coil pass across the middle line and occupy the- right upper part of the abdomen, those from the fifth cross back again to the left lumbar and iliac regions, and those of the sixth take possession of the false pelvis and the right iliac region (Fig. 188). Slight variations from this arrangement are not infrequent, but it occurs with sufficient frequency to be regarded as the normal. A failure in the readjustment of the relative lengths of the different parts of the colon may also occasionally occur, in which case the caecum will retain its embryonic position beneath the liver. The yolk-stalk is continuous with the intestine at the extremity of the loop which extends out into the umbilical coelom, and when the primary coils become apparent its point of attachment lies in the region of the sixth coil. As a rule, the caliber of the stalk does not increase proportionally with that of the intestine, and eventually its embryonic por- tion disappears completely. Occasionally, however, this portion of it does partake of the increase in size which occurs in the in- testine, and forms a blind pouch of vary- ing length, known as MeckeVs diverticulum Fig. 189.— c^cum of / ^\ Embryo of 10.2 cm, (see p. 116). „ . . „ ^ ^ ' c. Colon; t, ileum. The ccBcum has been seen to arise as a lateral outgrowth at a time when the intestine is first drawn out into the umbilicus. During subsequent development it continues to increase in size until it forms a conical pouch arising from the colon just where it is joined by the small intestine (Fig. 189). The enlargement of its terminal portion does not keep pace, how- ever, with that of the portion nearest the intestine, but it be- comes gradually more and more marked off from it by its lesser caliber and gives rise to the vermiform appendix. At birth the original conical form of the entire outgrowth is still quite evi- dent, though it is more properly described as funnel-shaped, but later the proximal part, continuing to increase in diameter at the 3o8 THE LIVER same rate as the colon, becomes sharply separated from the ap- pendix, forming the caecum of adult anatomy. Up to the time when the embryo has reached a length of 14 mm., the inner surface of the intestine is quite smooth, but when a length of 19 mm. has been reached, the mucous membrane of the upper portion becomes thrown into longitudinal folds, and later these make their appearance throughout its entire length (Fig. 190). Later, in embryos of 60 mm., these folds break up into numbers of conical processes, the villi, which increase in number Fig. 190. — Reconstruction of a Portion of the Intestine of an Embryo OF 28 MM. showing THE LONGITUDINAL POLDS FROM WHICH THE ViLLI ARE PORMED. — (Berry.) with the development of the intestine, the new villi appearing in the intervals between those already present. Villi are formed as well in the large as in the small intestine, but in the former they decrease in size as development proceeds and practically dis- appear toward the end of fetal life. In the early stages the endodermal lining of the digestive tract assumes a considerable thickness, the lumen of the oesophagus and upper part of the small intestine being reduced to a very small caliber. In later stages a rapid increase in the size of the lumen occurs, appar- ently associated with the formation of cavities or vacuoles in the endodermal epithelium. These increase in size, the neighboring cells arrange themselves in an epithelial layer around their walls and they THE LIVER 309 eventually break through into the general lumen. They are some- times sufficiently large to give the appearance of diverticula of the gut, but later they flatten out, their cavities becoming portions of the" general lumen. In the case of the duodenum the thickening of the endodermal lining proceeds to such an extent that in embryos of from 12.5 mm. to 14.5 mm. the lumen is completely obliterated immediately below the opening of the hepatic and pancreatic ducts. This condition is inter- esting in connection with the occasional occurrence in new-born children of an atresia of the duodenum. Under normal conditions, however, the lumen is restored by the process of vacuolization de- scribed above. Fig. 191. — Reconstruction of the Liver Outgrowths of Rabbit Embryos of (A) 5 MM. AND {B) OF 8 MM, B, Gall-bladder; d, duodenum; DV, ductus venosus; L, liver; p, dorsal pancreas; pm, ventral pancreas; rL, right lobe of the liver; S, stomach. — (Hammar.) The Development of the Liver.— The liver makes its appear- ance in embryos of about 3 mm. as a longitudinal groove upon the ventral surface of the archenteron just below the stomach and between it and the umbilicus. The endodermal cells lining the anterior portion of the groove early undergo a rapid proliferation, and form a solid mass which projects ventrally into the substance of a horizontal shelf, the septum transversum (see p. 321), attached to the ventral wall of the body. This solid mass (Fig. igi, L) forms the beginning of the liver proper, while the lower portion of 310 THE LIVER the groove, which remains hollow, represents the future gall- bladder (Fig. 191, B). Constrictions appearing between the intestine and both the hepatic and cystic portions of the organ gradually separate these from the intestine, until they are united to it only by a stalk which represents the ductus choledochus (Fig. 191). The further development of the liver, so far as its external form is concerned, consists in the rapid enlargement of the hepatic portion until it occupies the greater part of the upper half of the abdominal cavity, its ventral edge extending as far down as the umbilicus. In the rabbit its substance becomes divided into four lobes corresponding to the four veins, umbilical and vitelline, which traverse it, and the same condition occurs in the human embryo, although the lobes are not so clearly indicated upon the surface as in the rabbit. The two vitelline lobes are in close apposition and may almost be regarded as one, a median ventral lobe which embraces the ductus venosus (Fig. igi, B, DV), while the umbilical lobes are more lateral and dorsal and represent the right {rL) and left lobes of the adult liver. The remaining definite lobes, the caudate (Spigelian) and quadrate, are of later formation, standing in relation to the vessels which cross the lower surface of the liver. The ductus choledochus is at first wide and short, and near its proximal end gives rise to a small outgrowth on each side, one of which becomes the ventral pancreas (Fig. igi, B, pm). Later the duct elongates and becomes more slender, and the gall-bladder is constricted off from it, the connecting stalk becoming the cystic duct. The hepatic ducts are apparently developed from the Hver substance and are relatively late in appearing. Shortly after the hepatic portion has been differentiated its sub- stance becomes permeated by numerous blood-vessels (sinusoids) and so divided into anastomosing trabeculae (Fig. 192).' These are at first irregular in size and shape, but later they become more slender and more regularly cylindrical^ forming what have been termed the hepatic cylinders. In the center of each cyHnder, where the cells which form it meet together, a fine canal appears, the THE LIVER 311 beginning of a bile capillary ^ the cylinders thus becoming converted into tubes with fine lumina. This occurs at about the fourth week of development and at this time a cross-section of a cyHnder shows it to be composed of about three or four hepatic cells (Fig. 193, A), among which are to be seen groups of smaller cells (e) which are erythrocytes, the liver having assumed by this time its haematopoietic function (see p. 226). This condition of affairs persists until birth, but later the cylinders undergo an elongation, the cells of which they are composed slipping over one another Fig. 192. — Transverse Section through the Liver of an Embryo of Pour Months. in, Intestine; /, liver; W, Wolffian body. — {Toldt and Zuckerkandl.) apparently, so that the cylinders become thinner as well as longer and show for the most part only two cells in a transverse section (Fig. 193, B)\ and in still later periods the two cells, instead of lying opposite one another, may alternate, so that the cylinders become even more slender. The bile capillaries seem to make their appearance first in cylin- ders which lie in close relation to branches of the portal vein (Fig. 194), and thence extend throughout the neighboring cyHnders, anastomosing with capillaries developing in relation to neighboring portal branches. As the extension so proceeds the older capillaries 312 THE LIVER continue to enlarge and later become transformed into bile-duds (Fig. 194, C), the cells of the cylinders in which these capillaries were situated becoming converted into the epithelial Hning of the ducts. The lobules, which form so characteristic a feature of the adult liver, are late in appearing, not being fully developed until some time after birth. They depend upon the relative arrangement of the branches of the portal and hepatic veins ; these at first occupy distinct territories of the liver substance, being separated from one another by practically the entire thickness of the liver, although of Fig, 193. — Transverse Sections of Portions of the Liver of (A) a Fetus of Six Months and (B) a Child of Four Years. be, Bile capillary; e, erythrocyte; he, hepatic cylinder. — (Toldt and Zuckerkandl.) course connected by the sinusoidal capillaries which He between the hepatic cyHnders. During development the two sets of branches extend more deeply into the liver substance, each invading the territory of the other, but they can readily be distinguished from one another by the fact that the portal branches are enclosed within a sheath of connective tissue (Glisson's capsule) which is lacking to the hepatic vessels. At about the time of birth the branches of the hepatic veins give off at intervals bunches of terminal vessels, around which branches of the portal, vein arrange THE PANCREAS 313 themselves, the liver tissue becoming divided up into a number of areas which may be termed hepatic islands, each of which is sur- rounded by a number of portal branches and contains numerous dichotomously branching hepatic terminals. Later the portal branches sink into the substance of the islands, which thus become lobed, and finally the sinking in extends so far that the original island becomes separated into a number of smaller areas or lobules, each containing, as a rule, a single hepatic terminal (the intra- lobular vein) and being surrounded by a number of portal terminals {interlobular veins), the two systems being united by the capillaries which separate the cylinders contained within the area. The Fig. 194. — Injected Bile Capillaries of Pig Embryos of (A) 8 cm., (B) 16 cm., AND (C) OF Adult Pig. — (Hendrickson.) lobules are at first very small, but later they increase in size by the extension of the hepatic cylinders. Frequently in the human liver lobules are to be found containing two intralobular veins, a condition with results from an imperfect subdivision of a lobe of the original hepatic island. The liver early assumes a relatively large size , its weight at one time being equal to that of the rest of the body, and though in later embryonic stages its relative size diminishes, yet at birth it is still a voluminous organ, occupying the greater portion of the upper half of the abdominal cavity and extending far over into the left h3rpochondrium. Just after birth there is, however, a cessa- tion of growth, and the subsequent increase proceeds at a much slower rate than that of the rest of the body, so that its relative 314 THE PANCREAS size becomes still more diminished (see Chap. XVII). The cessa- tion of growth affects principally the left lobe and is accompanied by an actual degeneration of portions of the liver tissue, the cells disappearing completely, while the ducts and blood-vessels origi- nally present persist, the former constituting the vasa aherrantia of adult anatomy. These are usually especially noticeable at the left edge of the liver, between the folds of the left lateral ligament, but they may also be found along the line of the vena cava, around the gall-bladder, and in the region of the left longitudinal fissure. The Development of the Pancreas. — The pancreas arises a little later than the liver, as two or three separate outgrowths, one ». Pig. 195. — Reconstruction of the Stomach, Duodenum and Pancreas of a Human Embryo of 17.8 mm. (Thyng). A.Du, Antrum duodenale; C, stomach; D.choL, bile duct; D.cyst., cystic duct; D.hep., hepatic duct; D.panc.d., dorsal pancreatic duct; D.panc.v., ventral pancreatic duct; F, fundus of stomach; CE, oesophagus; Panc.d., dorsal pancreas; Panc.v., ven- tral pancreas; P.py., pyloric portion of stomach. from the dorsal surface of the duodenum (Fig. 195, Panc.d) usu- ally a little above the liver outgrowth, and one or two from the lower part of the common bile-duct . Of the latter outgrowths , that upon the left side may be wanting and, if formed, early disappears, while that of the right side {Panc.v.) continues its development LITERATURE 315 to form what has been termed the ventral pancreas. Both this and the dorsal pancreas continue to elongate, the latter lying to the left of the portal vein, while the former, at first situated to the right of the vein, later grows across its ventral surface so as to come into contact with the dorsal gland, with which it fuses so intimately that no separation line can be distinguished. The body and tail of the adult pancreas represent the original dorsal outgrowth, while the right ventral pancreas becomes the head. Both the dorsal and ventral outgrowths early become lobed, and the lobes becoming secondarily lobed and this lobation re- peating itself several times, the compound tubular structure of the adult gland is acquired, the very numerous terminal lobules becoming the secreting acini, while the remaining portions become the ducts. Of the principal ducts, there are at first two; that of the dorsal pancreas, the duct of Santorini, opens into the duode- num on its dorsal surface, while that of the ventral outgrowth, the duct of Wirsung, opens into the ductus choledochus. When the fusion of the two portions of the gland occurs, an anastomosis of branches of the two ducts develops and the proximal portion of the duct of Santorini may degenerate, so that the secretion of the entire gland empties into the common bile-duct through the duct of Wirsung. In the connective tissue which separates the lobules of the gland, groups of cells occur, which^have no connection with the ducts of the gland, and form what are termed the areas of Langer- hans. They arise by a differentiation of the cells which form the original pancreatic outgrowths, and have been distinguished in the dorsal pancreas of the guinea-pig while it is still a solid outgrowth. They gradually separate from the remaining cells of the out- growth and come to lie in the mesenchyme of the gland in groups into which, finally, blood-vessels penetrate. LITERATURE H. Ahrens: "Die Entwicklung der menschliche Zahne," Anat. Hefte, xxviii, 1913. E. T. Bell: "The Development of the Thymus," Amer. Journ. of Anat., v, 1906. J, M. Berry: "On^the Development of the Villi of the Human Intestine," AncU.y^ Anzeiger, xvi, 1900. 3l6 LITERATURE Gertrud Bien: "Zur Entwicklungsgeschichte des menschlichen Dickdarms," Anat. Hefte, XLix, 1913. L. Bolk: "Die Entwicklungsgeschichte der menschlichen Lippen," Anat. Hefte, XLiv, 1908. L, Bolk: "Ueber die Gaumenentwicklung und die Bedeutung der oberen Zahn- leiste beim Menschen," Zeit.filr Morphol. und AnthropoL, xiv, 191 1. J. Bracket: "Recherches sur le d^veloppement du pancreas et du foie," Journ. de VAnat. et de la Physiol., xxxn, 1896. O. C. Bradley: "A Contribution to the Morphology and Development of the Mam- malian Liver," Journ. Anat. and Physiol., XLiir, 1908. H. M. DE Burlet: "Die ausseren Formverhaltnisse der Leber beim menschlichen Embryo," Morphol. Jahrb., xlii, 1910. ■ R. V. Chamberlin: "On the Mode of Disappearance of the Villi from the Colon of Mammals," Anat. Record, iii, 1909. J. H. Chievitz: "Beitrage zur Entwicklungsgeschichte der Speicheldriisen," Archiv fur Anat. und Physiol., Anat. Ahth., 1885. H. Fox: "The Pharyngeal Pouches and Their Derivatives in the Mammalia," Amer. Journ. Anat., viii, 1908. K. Groschuff: "Ueber das Vorkommen eines Thymussegementes der vierten Kie- mentasche beim Menschen," Anat. Anzeiger, xvii, 1900. O. Grosser: "Zur Kenntnis des ultimobranchiaJen Korpers beim Menschen," Anat. Anzeiger, xxxvir, 1910. L. Grijnwald: "Ein Beitrag zur Entstehung und Bedeutung der Gaumenmandeln," Anat. Anzeiger, xxxvii, 19 10. J. A. Hammar: "Einige Plattenmodelle zur Beleuchtung der friiheren embryonal Leberentwicklung," Arch.f. Anat. undPhys., Anat. Ahth., 1893. J. A. Hammar: "Notiz iiber die Entwicklung der Zunge und der Mundspeichel- drusen beim Menschen," Anat. Anzeiger, xix, 1901. J. A. Hammar: "Studien tiber die Entwicklung des Vorderdarms und einiger angren- zender Organe," Arch. f. mikrosk. Anat., lix and lx, 1902. K. Helly: "Zur Entwickelungsgeschichte der Pancreasanlagen und Duodenal- papillen des Menschen," Archiv fUr mikrosk. Anat., lvi, 1900. K. Helly: "Studien iiber Langerhanssche Insein," Arch. fUr mikrosk. Anat., lxvii, 1907. W. F. Hendrickson: "The Development of the Bile-capillaries as revealed by Golgi's Method," Johns Hopkins Hospital Bulletin, 1898. W. His: "Anatomie menschlicher Embryonen," Leipzig, 1882-1886. F. Hochstetter: "Ueber die Bildung der primitiven Choanen beim Menschen," Anat. Anzeiger, vri, 1892. H. Holmdahl: "Zur Entwicklungsgegchichte des menschlichen Rectums," Anat. Hefte, LI, 1914. G. C. Huber: "On the Relations of the Chorda Dorsalis to the Pharyngeal Bursa or Median Pharyngeal Recess," Anat. Record, vi, 1912. N. W. Ingalls: "A Contribution to the Embryology of the Liver and Vascular System in Man," Anat. Record, n, 1908. C. M. Jackson: "On the Development and Topography of the Thoracic and Abdom- inal Viscera," Anat. Record, in, 1909. LITERATURE 317 ¥. P. Johnson: "The Development of the Mucous Membrane of the (Esophagus, Stomach and Small Intestine in the Human Embryo," Amer. Journ. Anat., x, 1910. ^-: — F. P. Johnson: "The Development of the Mucous Membrane of the Large Intestine and Vermiform Process in the Human Embryo," Amer. Journ. Anat., xiv, 1913. -F. P. Johnson: "The Development of the Rectum in the Human Embryo," Amer. Journ. Anat., xvi, 1914. E. Kallius: "Beitrage zur Entwicklung der Zunge, 3te Th. Saugetiere. I. Sus scrofa," Anat. Hefte, xli, 1910. F. Keibel: "Zur Entwickelungsgeschichte des menschlichen Urogenital-apparatus," Archiv fiir Anat. und Physiol., Anat. Abth., 1896. G. Killian: "Ueber die Bursa und Tonsilla phaiyngea.,^' Morphol. J ahrbuch,xiv, 1888. B. F. Kingsbury: "On the so-called ultimobranchial body of the mammalian embryo: man, Anat. Anzeiger,XL\ii, 1914. B. F. Kingsbury: "The development of the human pharynx, i, The pharyngeal derivatives," Amer. Journ. Anat., xviii, 1915. A. Kohn: "Die Epithelkorperchen," Ergebnisse der Anat. und Entwicklungsgesch., IX, 1899. E. Kreuter: "Die angeborenen Verschliessungen und Verengerungen des Darm- kanals in Lichte der Entwicklungsgeschichte," Deutsches Zeitschr. f. Chir.j Lxxrx, 1905. H. Kuster: "Zur Entwicklungsgeschichte der Langerhans'schen Inseln im Pancreas beim menschlichen Embryo," Arch, fiir mikrosk. Anat., lxiv, 1904. F. T. Lewis: "The Form of the Stomach in Human Embryos, etc." Amer. Journ. Anat., xiii, 1912. -F. T. Lewis and F. W. Thyng: "The Regular Occurrence of Intestinal Diverticula in Embryos of the Pig, Rabbit and Man," Amer. Journ. Anat., vii, 1908. F. P. Mall: "Ueber die Entwickelung des menschlichen Darmes und seiner Lage beim Erwachsenen," Archiv Jiir Anat. und Physiol., Anat. Abth., Supplement, 1897. F. P. Mall: "A Study of the Structural Unit of the Liver," Amer. Journ. of Anat., v, 1906. R. Mayer: "Ueber die Bildung des Recessus pharyngeus medius s. Bursa pharyngis in zusammenhang mit der Chorda bei menschlichen Embryonen," Anat. Anzeiger, xxxvii, 19 10. J. F. Meckel: " Bildungsgeschichte des Darmkanals der Saugethiere und nament- lich des Menschen," Archiv fiir Anat. und Physiol., iii, 181 7. T. MiRONESCu: "Ueber die Entwicklung der Langerhans'schen Inseln bei men- schlichen Embryonen," Arch, fiir mikrosk. Anat., lxxvt, 191 i. H. Moral: "Ueber die ersten Entwicklungsstadien der Glandula Submaxillaris," Anat. Hefte, xlvii, 1913. H. Moral: "Ueber die ersten Entwicklungsstadien der Glandula Parotis," Anat. Hefte, xlvii, 1913. E. H. Norris: "The early morphogenesis of the human thyroid gland." Amer. Journ. Anat. xxiv, 1918. W. J. Otis: "Die Morphogenese und Histogenese des Analhockers nebst Bemerk- 3l8 LITERATURE ungen iiber die Entwicklung der Sphincter ani externus beim Menschen," Anat. Hefte, XXX, 1906. J. L. Paulet: "Kopf und bucconasale Bildung eines menschlichen Embryo von 14.7 mm. Scheitelsteisslange," Archiv.f. mikr. Anat,, lxxvi, igio. R, M. Pearce: "The Development of the Islands of Langerhans in the Human Embryo," Amer. Journ. of Anat., 11, 1902. C. Rose: "Ueber die Entwicklung der Zahne des Menschen, Archiv fiir mikrsok. Anat., XXXVIII, 1891. G. Schorr: "Zur Entwickelungsgeschichte des secundaren Gaumens," Anat. Hefte, XXXVI, T908. G. Schorr: "Ueber Wolfsrachen von Standpunkt der Embryologie und patholog- ischen Anatomie," Arch, fiir patholog. Anat., cxcvii, 1909. H. Sidier: "Die Entwicklung des secundaren Gaumens beim Menschen." Anat, Anzeiger, xlvii, 191 5. A. Swaen: "Recherches sur le developpement du foie, du tube digestif, de I'arriere- cavit6 du peritoine et du mesentere," Journ. de I' Anat. et de la Physiol., xxxii, 1896, and xxxiii, 1897. X J. Tandler: "Zur Entwickelungsgeschichte des menschlichen Duodenum in friihen Embryonalstadien," Morphol. Jahrbuch, xxix, 1900. P. Thompson: "A Note on the Development of the Septum Transversum and the Liver," Journ. Anat. and Phys., xlii, 1908. F. W. Thyng: "Models of the Pancreas in Embryos of the Pig, Rabbit, Cat and Man," Amer. Journ. Anat., vii, 1908. C. ToLDT AND E. Zuckerkandl: "Ueber die Form and Texturveranderungen der menschlichen Leber wahrend des Wachsthums," Sitzungsher. der kais. Akad. Wissensch. Wien., Math.-Naturwiss. Classe, lxxii, 1875. F. Tourneux and p. Verdun: " Sur les premiers developpements de la Thyroide, du Thymus et des glandes parathyroidiennes chez I'homme," Journ. de VAnat. et de la Physiol., xxxiii, 1897. ,, F. Treves: "Lectures on the Anatomy of the Intestinal Canal and Peritoneum in Man," British Medical Journal, 1, 1885. CHAPTER XI THE DEVELOPMENT OF THE PERICARDIUM, THE PLEUROPERITONEUM AND THE DIAPHRAGM It has been seen (p. 230) that the heart makes its appearance at a stage when the greater portion of the ventral surface of the intes- tine is still open to the yolk-sac. The ventral mesoderm splits to form the somatic and splanchnic layers and the heart develops as a fold in the latter on each side of the median line, projecting into the coelomic cavity enclosed by the two layers (Fig. 138, A). As the constriction of the anterior part of the embryo proceeds the two heart folds are brought nearer together and later meet, so that the heart becomes a cyHndrical structure lyiftg in the median line of the body and is suspended in the coelom by a ventral band, the ventral mesocardium, composed of two layers of splanchnic meso- derm which extend to it from the ventral wall of the body, and by a similar band, the dorsal mesocardium, which unites it with the splanchnic mesoderm surrounding the digestive tract. The ven- tral mesocardium soon disappears (Fig. 138, C) and the dorsal one also vanishes somewhat later, so that the heart comes to lie freely in the coelomic cavity, except for the connections which it makes with the body-walls by the vessels which enter and arise from it. The coelomic cavity of the embryo does not at first communi- cate with the extra-embryonic coelom, which is formed at a very early period (see p. 70), but later when the splitting of the embry- onic mesoderm takes place the two cavities become directly continuous behind the heart, but not anteriorly, since the ventral wall of the body is formed in the heart region before the union can take place. It is possible, therefore, to recognize two portions in the embryonic coelom, an anterior one, the parietal cavity (His), which is never connected laterally with the extra-embryonic cavity, and a posterior one, the trunk cavity, which is so connected. 319 320 THE PERICARDIUM AND PLEURO-PERITONEUM The heart is situated in the parietal cavity, a considerable portion of which is destined to become the pericardial cavity. Since the parietal cavity lies immediately anterior to the still wide yolk-stalk, as may be seen from the position of the heart in the embryo shown in Fig. 54, it is bounded posteriorly by the yolk-stalk. This boundary is com- plete, however, only in the median line, the cavity being continuous on either side of the yolk-stalk with the trunk-cavity by passages which have been termed the recessus parietales (Fig. 196, Rca). Passing forward toward the heart in the splanchnic mesoderm which surrounds the yolk- stalk are the large vitelline veins, one on either side, and these shortly become so large as to bring the splanchnic mesoderm in which they lie in contact with the somatic mesoderm which forms the lateral walls of each recess. Fusion of the two layers of mesoderm along the course of the veins now takes place, and each recess thus becomes di- vided into two parallel passages, which have been termed the dorsal (Fig. 197, rpd) and ventral {rpv) parietal recesses. Later the two veins fuse in the upper portion of their course to form the beginning of the sinus venosus, with the result that the ventral recesses become closed below and their continuity with the trunk-cavity is inter- rupted, so that they form two blind pouches extending downward a short distance from the ventral portion of the floor of the parietal cavity. The dorsal recesses, however, retain their continuity with the trunk-cavity until a much later period. Om Rca Fig. 196, — Reconstruction OF A Rabbit Embryo of Eight Days, with the Pericardial Cavity Laid Open. A, Auricle; Aoh, aortic bulb; A, v., atrio- ventricular communica- tion; 'Om, vitelline vein; Pc, peri- cardial cavity; Rca, parietal recess; Sv, sinus venosus; V, ventricle. — (.His.) THE PERICARDIUM AND PLEURO-PERITONEUM 321 By the fusion of the vitelline veins mentioned above, there is formed a thick semilunar fold which projects horizontally into the. coelom from the ventral wall of the body and forms the floor of the ventral part of the parietal recess. This is known as the septum transversum, and besides containing the anterior portions of the vitelline veins, it also furnishes a passage by which the ductus Cuvieri, formed by the union of the jugular and cardinal veins, reach the heart. Its dorsal edge is continuous in the median line with the mesoderm surrounding the digestive tract just opposite the region where the hver outgrowth will form, but laterally this edge is free and forms the ventral walls of the dorsal parietal recess. An idea of the relations of the septum at this stage may be yom rpv Fig. 197. — Transverse Sections of a Rabbit Embryo showing the Division of THE Parietal Recesses by the Vitelline Veins. am. Amnion; rp, parietal recess; rpd and rpv, dorsal and ventral divisions of the parietal recess; vom, vitelline vein. — (Ravn.) obtained from Fig. 198, which represents the anterior surface of the septum, together with the related parts, in a rabbit embryo of nine days. The Separation of the Pericardial Cavity. — The septum trans- versum is at first almost horizontal, but later it becomes decidedly oblique in position, a change associated with the backward move- ment of the heart. As the closure of the ventral wall of the body extends posteriorly the ventral edge of the septum gradually slips downward upon it, while the dorsal edge is held in its former posi- tion by its attachment to the wall of the digestive tract and the ductus Cuvieri. The anterior surface of the septum thus comes 21 322 THE PERICARDIUM AND PLEURO-PERITONEUM to look ventrally as well as forward, and the parietal cavity, having taken up into itself the blind pouches which represented the ventral recesses, comes to lie to a large extent ventral to the poste- rior recesses. As may be seen from Fig. 198, the ductus Cuvieri, as they bend from the lateral walls of the body into the free edges of the septum, form a marked projection which diminishes con- siderably the opening of the dorsal recesses into the parietal cavity. am Fig. 198. — Reconstruction from a Rabbit Embryo of Nine Days showing the Septum Transversum from Above. am. Amnion; at, atrium; dc, ductus Cuvieri ;V^(/, dorsal parietal recess. — (Ravn.) In later stages this projection increases and from its dorsal edge a fold, which may be regarded as a continuation of the free edge of the septum, projects into the upper portions of the recesses and eventually fuses with the median portion of the septum attached to the wall of the gut. In this way the parietal cavity becomes a completely closed sac, and is henceforward known as the pericar- dial cavity, the original coelom being now divided into two portions, (i) the pericardial, and (2) the pleuro peritoneal cavities, the latter THE DIAPHRAGM 323 consisting of the abdominal coelom together with the two dorsal parietal recesses which have been separated from the pericardia 1_ (parietal) cavity and are destined to be converted into the pleural cavities. The Formation of the Diaphragm. — It is to be remembered that the attachment of the transverse septum to the ventral wall of the digestive tract is opposite the point where the liver outgrowth develops. When, therefore, the outgrowth appears, it pushes its way into the substance of the septum, which thus acquires a very considerable thickness, especially toward its dorsal edge, and it furthermore becom,es differentiated into two layers, an upper one, Fig. 199. — Diagrams of (A) a Sagittal Section of an Embryo showing the Liver Enclosed within the Septum Transversum; {B) a Frontal Section of THE Same; (C) a Frontal Section of a Later Stage when the Liver has Sepa- rated FROM THE Diaphragm. All, Allantois; CI, cloaca; D, diaphragm; Li, liver; Ls, falciform ligament of the liver; M, mesentery; Mg, mesogastrium; Pc, pericardium; S, stomach; ST, septum transversum; U, umbilicus. which forms the floor of the ventral portion of the pericardial cavity and encloses the Cuvierian ducts, and a lower one which contains the liver. The upper layer is comparatively thin, while the lower forms the greater part of the thickness of the septum, its posterior surface meeting the ventral wall of the abdomen at the level of the anterior margin of the umbilicus (Fig. 199, A). In later stages of development the layer containing the liver becomes separated from the upper layer by two grooves which, 324 THE DIAPHRAGM appearing at the sides and ventrally immediately over the liver (Fig. 199, B), gradually deepen toward the median line and dor- sally. These grooves do not, however, quite reach the median line, a portion of the lower layer of the septum being left in this region as a fold, situated in the sagittal plane of the body and attached above to the posterior surface of the upper layer and below to the anterior surface of the liver, beyond which it is con- tinued down the ventral wall of the abdomen to the umbilicus (Fig. 199, C, Ls). This is the falciform ligament of the liver of adult anatomy, and in the free edge of its prolongation down the ventral wall of the abdomen the umbilical vein passes to the under surface of the liver, while the free edge of that portion which lies between the liver and the digestive tract contains the vitelline (portal) vein, the common bile-duct, and the hepatic artery. The diagram given in Fig. 199 will, it is hoped, make clear the mode of formation and the relation of this fold, which, in its entirety, con- stitutes what is sometimes termed the ventral mesentery. And not only do the grooves fail to unite in the median line, but they also fail to completely separate the liver from the upper layer of the septum dorsally, the portion of the lower layer which persists in this region forming the coronary ligament of the hver. The portion of the lower layer which forms the roof of the grooves be- comes the layer of peritoneum covering the posterior surface of the upper layer (which represents the diaphragm), while the portion which remains connected with the liver constitutes its peritoneal investment. In the meantime changes have been taking place in the upper layer of the septum. As the rotation of the heart occurs, so that its atrial portion comes to lie anterior to the ventricle, the Cuvier- ian ducts are drawn away from the septum and penetrate the pos- terior wall of the pericardium, the separation being assisted by the continued descent of the attachment of the edge of the septum to the ventral wall of the body. During the descent, when the upper layer of the septum has reached the level of the fourth cer- vical segment, portions of the myotomes of that segment become prolonged into it and the layer assumes the characteristics of the THE PLEURA 325 diaphragm, the supply of whose musculature from the fourth cervical nerves is thus explained. The PleurcB. — The diaphragm is as yet, however, incomplete dorsally, where the dorsal parietal recesses are still in continuity with the trunk-cavity. With the increase in thickness of the septum transversum, these recesses have acquired a considerable length antero-posteriorly, and into their upper portions the out- growths from the lower part of the pharynx which form the lungs (see p. 334) begin to project. The recesses thus become trans- formed into the pleural cavities, and as the diaphragm continues to descend, slipping down the ventral wall of the body and drawing with it the pericardial cavity, the latter comes to He entirely ventral to the pleural cavities. The free borders of the diaphragm, which now form the ventral boundaries of the openings by which the pleural and peritoneal cavities communicate, begin to approach the dorsal wall of the body, with which they finally unite and so complete the separation of the cavities. The pleural cavities continue to enlarge after their separation and, extending laterally, pass between the pericardium and the lateral walls of the body until they finally almost completely surround the pericardium. The in- tervals between the two pleurae form what are termed the mediastina. The downward movement of the septum transversum extends through a very considerable interval, which may be appreciated from the diagram shown in Fig. 200. From this it may be seen that in early embryos the septum is situated just in front of the first cervical segment and that it lies very obliquely, its free edge being decidedly posterior to its ventral attachment. When the down\^ard displacement occurs, the ventral edge at first moves more rapidly than the dorsal, and soon comes to lie at a much lower level. The downward movement continues throughout the entire length of the cervical and thoracic regions, and when the level of the tenth thoracic segment is reached the separation of the pleural and peritoneal cavities is completed, and then the dorsal edge ^ begins to descend more rapidly than the ventral, so that the diaphragm again becomes oblique in the same sense as in the beginning, a position which it retains in the adult. 326 THE PERITONEUM t«<^U/ OU/tnit£ DaUai The Development of the Peritoneum. — -The peritoneal cavity is developed from the trunk-cavity of early stages and is at first in free communication on all sides of the yolk-stalk with the extra- embryonic coelom. As the ventral wall of the body develops the two cavities become more and more separated, and with the formation of the umbilical cord the separation is complete. Along the mid-dorsal line of the body the archenteron forms a projection into the cavity and later moves further out from the body-wall into the cavity, pushing in front of it the peritoneum, which thus comes to surround the intestine, forming its serous coat, and from it is continued back to the dorsal body-wall forming the mesentery. It has already been seen that on the separation of the liver from the septum transversum, the tissue of the latter gives rise to the peritoneal covering of the liver and of the posterior surface of the diaphragm, and also to the ventral mesentery. When the separ- ation is taking place, the rotation of the stomach already described ( p. 303) occurs, with the result that the portion of the ventral mesentery which stretches between the lesser curvature of the stomach and the liver shares in the rotation and comes to lie in p, plane practically at right angles with that of the falciform ligament, its surfaces looking dorsally and ventrally and its free edge being directed toward the right. This portion of the ventral mesentery forms what is termed the lesser omentum, and between it and the dorsal surface of the stomach as the ventral boundaries, and the dorsal wall of the abdominal cavity dorsally, there is a cavity, whose floor is formed by the dorsal mesentery of the stomach, the meso- FiG. 200. — Diagram show iNG THE Position of the Dia PHRAGM IN Embryos of Dif FERENT Ages. — {Mall.) THE PERITONEUM 327 gastrium, the roof by the under surface of the left half of the liver, while to the right it communicates with the general peritoneal- cavity dorsal to the free edge of the lesser omentum. This cavity is known as the bursa omentalis (lesser sac of the peritoneum) , and the opening into it from the general cavity or greater sac is termed \h& epiploic foramen (foramen of Winslow). Later, the floor of the lesser sac is drawn downward to form a broad sheet of peri- toneum lying ventral to the coils of the small intestine and con- sisting of four layers; this represents the great omentum of adult anatomy (Fig. 204). Although the form assumed by the bursa omentalis is asso- ciated with the rotation of the stomach, it seems probable that its real origin is independent of that process (Broman). The subserous tissue of the transverse septum is at first thick and in- cludes not only the hver, but also the pancreas and the portion of the digestive tract which becomes the stomach and the upper part of the duodenum (Fig. 199, A). The shrinkage of this tissue, by which these organs become separated from the septum, cannot take place evenly on account of the relations which the organs bear to one another, so that on the right side certain peritoneal recesses are formed, one between the right lung and the stomach, a second between the liver and the stomach, and a third between the pancreas and the same structure. In man these three recesses communicate with one another to form the primary bursa omentalis, and open by a common epiploic foramen into the general peritoneal cavity. The rotation of the stomach, which takes place later, merely serves to modify the original bursa. In the human embryo a small recess also forms upon the left side between the left lung and the stomach. Later it separates from the rest of the bursa omentalis and passes up along the side of the oesoph- agus, coming to lie on its right side between it and the diaphragm. It gives rise to a small serous sac that lies beneath the infracardial lobe of the right lung, when this is present, and hence has been termed the infracardial bursa. Below the level of the upper part of the duodenum the ventral mensentery is wanting; only the dorsal mesentery occurs. So 328 THE PERITONEUM long as the intestine is a straight tube the length of the intestinal edge of this mesentery is practically equal to that of its dorsal attached edge. The intestine, however, increasing in length much more rapidly than the abdominal walls, the intestinal edge of the mesentery soon becomes very much longer than the at- tached edge, and when the intestine grows out into the umbiHcal coelom the mesentery accompanies it (Fig. 201). As the coils of the intestine develop, the intestinal edge of the mesentery is thrown into corresponding folds, and on the return of the intestine to the abdominal cavity the mesentery is thrown into a somewhat funnel-like form by the twisting of the intestine to form its primary loop (Fig. 202). All that portion of the mes- entery which is attached to the part of the intestine which will later become the jejunum, ileum, ascending and transverse colon, is at- tached to the body-wall at the apex of the funnel, at a point which lies to the left of the duodenum. Up to this stage or to about the middle of the fourth month the mesentery has retained its attachment to the median line of the dorsal wall of the abdomen throughout its entire length, but, later, fusions of certain whereby the original con- dition is greatly modified. One of the earl- iest of these fusions results in the formation of the transverse mesocolon, whose attach- ment to the dorsal wall of the abdomen is at right angles to the original line of attachment of the mesentery. This condition is brought about in the following manner. By the twisting of the primary loop of 'the intestine the ascending and descending colons are brought into'^apposition with the lateral walls of the abdominal cavity, while the transverse colon, since it passes ventral to the duodenum, has a more ventral position (Fig. 202). The right layer of the portion of the mesentery attached to the ascending Fig. 201. — Diagram showing the arrange- ment of the m esentery AND Visceral Branches OF THE Abdominal portions OCCUr Aorta in an Embryo OF Six Weeks. p. Pancreas; S, stomach; Sp, spleen.— (ToW/.) THE PERITONEUM 329 colon is thus brought into contact with the parietal peritoneum lining the right wall of the abdomen and fuses with it and, sinii- larly, the left layer of the descending mesocolon fuses with the parietal peritoneum of the left wall of the abdomen, as is shown in Fig. 204. The ascending and descending colons thus lose their mesentery and become permanently fixed in position, but since the transverse mesocolon does not come into contact with the parietal peritoneum, it remains distinct and has acquired a trans- verse line of attachment to the body wall. Fig. 202. — Diagrams Illustrating the Development of the Great Omentum AND THE Transverse Mesocolon. bid. Caecum; dd, small intestine; dg, yolk-stalk; di, colon; du duodenum; gc, greater curvature of stomach; gg, bile duct; gn, mesogastrium; k, point where the loops of the intestine cross; mc, mesocolon; md, rectum; mes, mesentery; wf, vermi- form appendix. — {Her twig.) This hne of attachment passes across the duodenum and forces this portion of the intestine against the dorsal abdominal wall, with the result that its dorsal mesentery disappears, becoming con- verted into subserous areolar tissue. The duodenum and pan- creas, which latter is essentially an outgrowth from the duodenum into the dorsal mesentery, thus assume the position which char- acterizes them in the adult, becoming retroperitoneal and lying behind the root of the transverse mesocolon. 330 THE PERITONEUM The fusion of the mesentery of the ascending and descending colon remains incomplete in a considerable number of cases (one-fourth to one- third of all cases examined), and in these the colons are not perfectly fixed to the abdominal wall. It may also be pointed out that the caecum and appendix, being primarily a lateral outpouching of the intestine, do not possess any true mesentery, but are completely enclosed by peritoneum. Usually a falciform fold of peritoneum may be found extending along one surface of the appendix to become continuous with the left layer of the mesentery of the ileum. This, however, is not a true mesentery, and is better spoken of as a mesenteriole. <'"''•"'" . Fig. 203. — Diagrams Illustrating the Manner in Which the Fixation of THE Descending Colon (C) takes Place. One other fusion is still necessary before the adult condition of the mesentery is acquired. The great omentum consists of two folds of peritoneum which start from the greater curvature of the stomach and pass downward to be reflected up again to the dorsal wall of the abdomen, which they reach just anterior to (above) the line of attachment of the transverse mesocolon (Fig. 204 A). At first the attachment of the omentum is vertical, since it repre- sents the mesogastrium, but later, by fusion with the parietal peritoneum, it assumed a transverse direction. By this change the lower layer of the omentum is brought in contact with the upper layer of the transverse mesocolon and a fusion and de- generation of the two results (Fig. 204 5), a condition which brings it about that the omentum seems to be attached to the transverse colon. The transverse mesocolon, as it occurs in the adult, really THE PERITONEUM 33'^ consists partly of a portion of the original transverse mesocolon and partly of a layer of the great omentum. _ _ By these various changes the line of attachment of the mesen- tery to the dorsal wall of the body has become somewhat compli- cated and has departed to a very considerable extent from its original simple vertical arrangement. If all the viscera be re- FiG. 204. — Diagrams showing the* Development of the Great Omentum and ITS Fusion with the Transverse Mesocolon. B, bladder; c, transverse colon; d, duodenum; Li, liver; p, pancreas; 2?, rectum; S. stomach; U. uterus. — (After Allen Thomson.) moved from the body of an adult and the mesentery be cut close to the hne of its attachment, the course of the latter will be seen to be as follows (Fig. 205) : Descending from the under surface of the diaphragm are the lines of attachment of the falciform liga- ment, which on reaching the liver spread out to become the coro- nary and lateral ligaments of that organ, all these structures being derivatives of the ventral mesentery. A little to the left of the median plane these lines become continuous with those of the mesogastrium which curve downward toward the left and are 332 THE PERITONEUM continued into the transverse lines of the transverse mesocolon. Between these last, in a slight prolongation, there may be seen to the right the cut end of the first portion of the duodenum as it passes back to the dorsal wall of the abdomen, and at about the Fig. 205. — The Lines of Reflection of the Peritoneum from the Abdom- inal Wall to the Various Organs. — {From Morris' Anatomy.) ac. Area of attachment of ascending colon; BO, bursa omentalis; cor. I., coronary- ligament; d.c, area of attachment of descending colon; Du, duodenuna; EF, epiploic foramen; FL, falciform ligament; mg, mesogastrium; mes, mesentery of small intes- tine; ees, oesophagus; R, rectum; Sc, sigmoid mesocolon; tr. I., left triangular liga- ment; tr.mc, transverse mesocolon; v.c.i, inferior vena cava. mid-dorsal line the cut end of its last part becomes visible as it passes ventrally again to become the jejunum. From the trans- LITERATURE 333 verse mesocolon three lines of attachment pass downward; the two lateral broad ones represent the lines of fixation of the as- cending and descending colons, while the narrower median one which curves to the right, represents the attachment of the mesentery of the small intestine other than the duodenum. Fin- ally, from the lower end of the fixation line of the descending colon the mesentery of the sigmoid colon is continued downward. The special developments of the peritoneum in connection with the genito-urinary apparatus will be considered in Chapter XIII. LITERATURE I. Broman: "Ueber die Entwicklung und Bedeutung der Mesenterien und der Korpenhohlen bei den Wirbeltieren," Ergehn. der Anat. u. Entw., xv, 1906. A. Bracket: "Die Entwdckelung der grossen Korperhohlen und ihre Trennung von Einander," Ergehnisse der Anat. und Entwickelungsgesch., vii, 1898. W. His: "Mittheilungen zur Embryologie der Saugethiere und des Menschen," Archiv fur Anat. und Physiol., Anat. Abth., 1881. F. P. Mall: "Development of the Human Coelom," Journat-of Morphol., xii, 1897. F. P. Mall: "On the Development of the Human Diaphragm," Johns Hopkins Hospital Bull., xii, 1901. E. Ravn: "Ueber die Bildung der Scheidewand zwischen Brust-und Bauchhohle in Saugethierembryonen," Archiv fiir Anat. und Physiol., Anat. Ahlh., 1889. A. Swaen: "Recherches sur le d6veloppement du foie, du tube digestif, de I'arriere- cavit6 du peritoine et du mesentere," Journ. de I' Anat. et de la Physiol., xxxii, 1896; XXXIII, 1897. C. Toldt: "Bau und Wachstumsveranderungen der Gekrose des menschlichen Darmkanals," Denkschr. der kais. Akad. Wissensch. Wien, Math.-Naturwiss. Classe, xli, 1879. C. Toldt: "Die Darmgekrose und Netze im gesetzmassigen und gestezwidrigen Zustand," Denkschr. der kais. Akad. Wissensch. Wien. Math.-Naturwiss. Classe, LVI, 1889. F. Treves: "Lectures on the Anatomy of the Intestinal Canal and Peritoneum," British Medical Journal, i, 1885. CHAPTER XII THE DEVELOPMENT OF THE ORGANS OF RESPIRATION RP The Development of the Lungs.— The first indication of the lungs and trachea is found in embryos of about 3.2 mm. in the form of a groove on the ventral surface of the oesophagus, at first extending almost the entire length of that portion of the digestive tract. As the oesophagus lengthens the lung groove remains con- nected with its upper portion (Fig. 184 A)^ and furrows which appear along the line of junction of the groove and the oesophagus gradually deepen and separate the two structures (Fig. 184, B). The separation takes place earUest at the lower end of the groove and thence extends upward, so that the groove is transformed into a Pig. I06.-P0RT10N OF A Section cylindrical pouch lying ventral to THROUGH AN Embryo OF THE FouRTH thc ocsophagus aud dorsal to the ^T Aorta; DC, ductus Cuvieri; L, heart and Opening with the oeso- lung; O. oesophagus; 2?P, parietal re- phagUS iutO the terminal portioU of cess; VOm, vitelline vein. — (Toldt.) the pharynx. Soon after the separation of the groove from the oesophagus its lower end becomes enlarged and bilobed, and since this lower end Hes, with the oesophagus, in the median attached portion of the dorsal edge of the septum transversum, the lobes, as they en- large, project into the dorsal parietal recesses (Fig. 206), and so be- come surrounded by the peritoneal lining of the recesses, which later become the pleural cavities. The lobes, which represent the lungs, do not long remain simple, but bud-like processes arise from their cavities, three ap- 334 THE LUNGS 335 pearing in the right lobe and two in the left (Fig. 207, A), and as these increase in size and give rise to additional outgrowths, the structure of the lobes rapidly becomes complicated (Fig. 207, B and C) . The lower primary process on each side may be regarded as a prolongation of the bronchus, while the remaining process or processes represent lateral outgrowths from it. Considerable difference of opinion has existed as to the nature of the further branching of the bronchi, some authors regarding it as a succession -'-.ip c^. B C Fig. 207. — Reconstruction of the Lung Outgrowths of Embryos of (A) 4,3, (B) 8.5, AND (C) 10.5 MM. Ap, Pulmonary artery; Ep, eparterial bronchus; Vp, pulmonary vein; /, seoond lateral bronchus; II, main bronchi. — (His.) of dichotomies, one branch of each of these placing itself so as to be in the line of the original main bronchus, while the other comes to resemble a lateral outgrowth, and other observers have held that the main bronchus has an uninterrupted growth, all other branches being lateral outgrowths from it, and the branching therefore a monopodial process. The recent thorough study by Flint of thexievelopment of the lung of the pig shows that, in that form at least, the branching is a monopodial one, and that from the main bronchus as it elongates four sets of secondary growths develop, namely, a strong lateral, a dorsal, a ventral, and a weak and variable medial set. There is a general tendency for the individual branches of the 336 THE LUNGS various sets to be arranged in regular succession and for their development to be symmetrical in the two lungs. But on ac- count of the necessity under which the lungs are placed of adapt- ing themselves to the neighboring structures and at the same time affording a respiratory surface as large as possible, an amount of asymmetry supervenes. Thus, it has already been noted that in the earliest branching a single lateral bronchus is formed in the left lung and two in the right. The uppermost of these latter, the first lateral bronchus, is unrepresented in the left lung, and is peculiar in that it lies behind the right pulmonary artery (Fig. 207, C), or in the adult, after the recession of the heart, above it, whence it is termed the eparterial bronchus. Its absence on the left side is perhaps due to its suppression to permit the normal recession of the aortic arch (Flint). So, too, the inclination of the heart causes a suppression of the second ventral bronchus in the left lung, but at the same time it affords opportunity for an excessive development of the corresponding bronchus of the right lung, which pushes its way between the heart and the diaphragm and is known as the infracardiac bronchus. As soon as the unpaired first lateral bronchus and the paired second lateral bronchi are formed mesenchyme begins to collect around each of them and also around the main bronchi, the lobes of the adult lung, three in the right lung and two in the left, being thus outHned. A development of mesenchyme also takes place around the excessively developed right second ventral bronchus, and sometimes produces a well-marked infra-cardiac lobe in the right lung. In later stages the various bronchi of each lobe give rise to Pig. 208. — Diagram of THE Pinal Branches of the Mammalian Bronchi. A, Atrium; B, bronchus; S, air-sac . — ( Miller.) THE LARYNX 337 additional branches and these again to others, and the mesen- chyme of each lobe grows in between the various branches. At first the amount of mesenchyme separating the branches is com- paratively great, but as the branches continue to develop, the growth of the mesenchyme fails to keep pace with them, so that in later stages the terminal enlargements are separated from one another by only very thin partitions of mesenchyme, in which the pulmonary vessels form a dense network. The final branching of each ultimate bronchus of bronchiole results in the forma- tion at its extremity of from three to five enlargements, the atria (Fig. 209, A)^ from which arise a number of air-sacs {S) whose walls are pouched out into sHght diverticula, the air-cells or alveoli. Such a combination of atria, air- sacs, and air-cells constitutes a lobule, and each lung is composed of a large number of such units. The greater part of the original pulmonary groove becomes con- verted into the trachea, and in the mesenchyme surrounding it the incomplete cartilaginous rings develop at about the eighth or ninth week. The cells of the epithelial lining of the trachea and bronchi remain columnar or cubical in form and become ciliated at about the fourth month, but those of the epitheHum of the air- sacs become greatly flattened and constitute an exceedingly thin layer of pavement epithelium. The Development of the Larynx.— The opening of the upper end of the pulmonary groove into the pharynx is situated at first just behind the fourth branchial furrow and is surrounded an- teriorly and laterally by the U-shaped ridge already described (p. 296) as the furcula, this separating it from the posterior por- 22 Fig. 209. — Reconstruction of THE Opening into the Larynx in AN Embryo of Twenty-eight Days, Seen from Behind and Above, the Dorsal Wall of the Pharynx being Cut Away. CO, Cornicular, and cu, cuneiform tubercle; Ep, epiglottis; T, unpaired portion of the tongue. — (Kallius.) ^^S THE LARYNX tion of the tongue (Fig. i8o). The anterior portion of this ridge, which is apparently derived from the ventral portions of the third branchial arch, gradually increases in height and forms the epiglottis, while the lateral portions, which pass posteriorly into the margins of the pulmonary groove, form the ary epiglottic folds. When the pulmonary groove separates from the oesophagus, the opening of the trachea into the pharynx is somewhat slit-like and is bounded laterally by the aryepiglottic folds, whose margins present two elevations which may be termed the cornicular and cuneiform tubercles (Fig. 209, co and cu, and Fig. 177). The opening is, however, for a time almost obHterated by a thickening of the epithehum covering the ridges, and it is not until the tenth or eleventh week of development that it is re-established. Later Pig. 210. — Reconstruction of the Mesenchyme Condensations which Repre- sent THE Hyoid and Thyreoid Cartilages in an Embryo of Forty Days. The darkly shaded areas represent centers of chondrification. c.ma. Greater cornu of hyoid; c.mi, lesser cornu; Th, thyreoid cartilage. — (Kallius.) than this, at the middle of the fourth month a linear depression makes its appearance on the mesial surface of each aryepiglottic fold, forming the beginning of the ventricle, and although at first the depression lies horizontally, its lateral edge later bends an- teriorly, so that its surfaces look outward and inward. The lips which bound the opening of the ventricle into the laryngeal cavity give rise to the ventricular and vocal folds. The cartilages of the larynx can be distinguished during the seventh week as condensations of mesenchyme which are but indistinctly separated from one another. The thyreoid cartilage is represented at this stage by two lateral plates of mesenchyme, separated from one another both ventrally and dorsally, and each THE LARYNX 339 of these plates undergoes chondrifi cation from two separate centers (Fig. 210). These, as they increase in size, unite together and send prolongations ventrally which meet in the mid-ventral line with the corresponding prolongations of the plates of the opposite side, so as to enclose an area of mesench3nne into which the chondrification only extends at a later period, and occasionally fails to so extend, producing what is termed a foramen thyreoideum. The mesenchymal condensations which represent the cricoid and arytenoid cartilages are continuous, but each arytenoid has a distinct center of chondrification, while the cartilage of the cricoid appears as a single ring which is at first open dorsally and only later becomes complete. The epiglottis cartilage resembles the thyreoid in being formed by the fusion of two originally distinct cartilages, from each of which a portion separates to form the cuneiform cartilages (cartilages of Wrisherg) which produce the tu- bercles of the same name on the aryepiglottic fold, while the cor- niculate cartilages {cartilages of Santorini) are formed by the separation of a small portion of cartilage from each arytenoid. The formation of the thyreoid cartilage by the fusion of two pairs of lateral elements finds an explanation from the study of the comparative anatomy of the larynx. In the lowest group of the mammalia, the Montremata, the four cartilages do not fuse together and are very evidently serially homologous with the car- tilages which form the cornua of the hyoid. In other words, the thyreoid results from the fusion of the fourth and fifth branchial cartilages. The cricoid, in its development, ptresents such striking similarities to the cartilaginous rings of the trachea that it is probably to be regarded as the uppermost cartilage of that series, but the epiglottis seems to be a secondary chondrification in the glossolaryngeal fold (Schaffer). The arytenoids possibly rep- resent an additional pair of branchial cartilages, such as occur in the lower vertebrates (Gegenbaur). These last arches have undergone almost complete reduction in the mammalia, the cartilages being their only representatives, but, in addition to the cartilages, the fourth and fifth arches have also preserved a portion of their musculature, part of which becomes 340 LITERATURE transformed into the muscles of the larynx. Since the nerve which corresponds to these arches is the vagus, the supply of the larynx is derived from that nerve, the superior laryngeal nerve probably corresponding to the fourth arch, while the inferior (recurrent) answers to the fifth. The course of the recurrent nerve finds its explanation in the relation of the nerve to the fourth branchial artery. When the heart occupies its primary position ventral to the floor of the pharynx, the inferior laryngeal nerve passes transversely inward to the larynx beneath the fourth branchial artery. As the heart recedes the nerve is caught by the vessel and is carried back with it, the portion of the vagus between it and the superior laryngeal nerve elongating until the origins of the two laryngeal nerves are separated by the entire length of the neck. Hence it is that the right recurrent nerve bends upward behind the right subclavian artery, while the left curves beneath the arch of the aorta (see Fig. 151), LITERATURE J. M. Flint: "The Development of the Lungs," Amer. Journ. Anat., vi, 1906. J. E. Frazer: "The Development of the Larynx," Journ. Anat. and Phys., xliv, 1910. E. Goppert; "Ueber die Herkunft der Wrisbergschen Knorpels," MorphoL Jahruch, XXI, 1894. W. His: "Zur Bildungsgeschichte des Lungen beim menschiichen Embryo," Archiv filr Anat. und Physiol., Anat. Abth., 1887. E. Kallius: "Beitrage zur Entwickelungsgeschichte des Kehlkopfes," Anat. Hefte, IX, 1897. K. Kallius: "Die Entwickelung des menschiichen Kehlkopfes," Verhandl. der Anat. Gesellsch., xn, 1898. A. Lisser: "Studies on the Development of the Human Larynx," Amer. Journ. Anat., XII, 1911. / A. Narath: "Der Bronchialbaum der Saugethiere und des Menschen," Bibliotheca Medica, Abth. A, Heft 3, 1901. J. Schaffer: "Zur Histologic, Histogenese und phylogenetischen Bedeutung der Epiglottis," Anat. Hefte, xxxiii, 1907. A. SouLiE AND E. Bardier: "Recherches sur le developpement du larynx chez I'homme," Journ. de I' Anat. et de la Physiol., xliii, 1907. CHAPTER XIII THE DEVELOPMENT OF THE URINOGENITAL SYSTEM The excretory and reproductive systems of organs are so closely related in their development that they must be considered to- gether. They both owe their origin to the mesoderm which constitutes the intermediate cell-mass (p. 80), this, at an early period of development, becoming thickened so as to form a ridge projecting into the dorsal portion of the coelom and forming what is known as the Wolffian ridge (Fig. 211, wr). The greater portion of the substance of this ridge is concerned in- the de- ^^^c \ J t "^c-; wr Fig. 211, — Transverse Section through the Abdominal Region of a Rabbit Embryo of 12 mm. a, Aorta; gl, glomerulus; gr, genital ridge; m, mesentery; nc, notochord; /, tubule of mesonephros; wd. Wolffian duct; wr. Wolffian ridge. — (Mihalkovicz.) velopment of the primary and secondary excretory organs, but on its mesial surface a second ridge appears which is destined to give rise to the ovary or testis, and hence is termed the genital ridge (gr). The development of the excretory organs is remarkable in that three sets of organs appear in succession. The first of these, the pronephros, exists only in a rudimentary condition in the human embryo, although its duct, the pronephric or Wolffian duct, under- 341 342 THE PRONEPHROS goes complete development and plays an important part in the development of the succeeding organs of excretion and also in that of the reproductive organs. The second set , the mesonephros or Wolffian body, reaches a considerable development during em- bryonic life, but later, on the development of the final set, the definite kidney or metanephros, undergoes degeneration, portions only persisting as rudimentary structures associated for the most part with the reproductive organs. The Development of the Pronephros and the Pronephric Duct. — The first portions of the excretory system to make their appearance are the pronephric or Wolffan ducts, which develop as im^ ,^f. r/i. Fig. 212. — Transverse Section through Chick Embryo of about Thirty-six Hours. en, Endoderm; im, intermediate cell mass; ms, mesodermic somite; nc, notochord; so, somatic, and sp, splanchnic mesoderm; wd. Wolffian duct. — (Waldeyer.) outgrowths of the dorsal walls of the intermediate cell masses. At first the outgrowths are solid cords of cells (Fig. 212, wd), but later a lumen appears in the center of each and the canal so formed from each intermediate cell mass, bending backward at its free end, comes into contact and fuses with the canal from the next succeeding segment. Two longitudinal canals, the pronephric or Wolffian ducts, are thus formed, with which the cavities of the intermediate cell masses communicate. The formation of the ducts begins in the anterior segments before the segmentation of the posterior portions of the mesoderm has taken place, and the further backward extension of the ducts takes place independently of the formation of excretory tubules, apparently by a process of terminal growth. The free end of each duct comes into intimate relation with the ectoderm above it, so much so that its posterior THE PRONEPHROS 343 portion has been held by some observers to be formed from that layer, but it seems more probable that the relation to the ectoderm- is a secondary process and that the ducts are entirely of meso- dermal origin. They reach the cloaca in embryos of a little over 4 mm., and later they unite with that organ, so that their lumina open into its cavity. The pronephric tubules make their appearance in embryos of about 1.7 mm., while as yet there are only nine or ten mesodermic somites, and they are formed from the intermediate cell masses of the seventh to the thirteenth or four- teenth segment, and perhaps from those situated still more anteriorly. They attain their maximum development in embryos of about 3.5 mm., one of this size having an arrangement of the ex- cretory apparatus as shown in Fig. 213. On the left side, beginning at the seventh segment and extending back to the thirteenth, are a number of pronephric tubules, whose inner ends have united to form the pronephric or Wolffian duct. This, however, has grown backward as far as the sixteenth segment, into the region in which the mesonephros has begun to differentiate. It will be noted that the pronephric tubules are not exactly metameric in their arrangement, some of the segments possessing two. On the right side the first prone- phric tubule occurs in the ninth segment, but in the two preceding ones the degenerated remains of two additional tubules occur. For the pronephric system begins to degenerate at its anterior end almost before the most posterior tubules have formed, and with Fig. 213. — Diagram of THE Arrangement of the Excretory Apparatus of an Embryo of 3.5 mm. The unstippled structures with heavy outlines represent the pronephric system; the solid black bodies, degenerated pronephric tubules; the stip- pled structures, differentiating mesonephric tubules, termi- nating, in the unsegmented nephrogenic c o r d. ^- (7. C. Watt.) 344 THE PRONEPHROS the disappearance of the tubules there is a disappearance of the corresponding portions of the Wolffian duct. In the embryo from which Fig. 213 was drawn the excretory apparatus of the right side was a little further advanced in development than that of the left side, and hence the occurrence of degenerated tubules on the former only. Each pronephric tubule, when fully formed, consists of a portion which unites it to the Wolffian duct, and opens at its other end into an enlargement, the pronephric chamber (Fig. 214, pc), which, on its part opens into the coelomic cavity by means of a nephrostome canal. In the neighborhood of the coelomic open- FiG. 214. — Diagram showing the Structure of a Fully Developed Pronephric Tubule. Ao, Aorta; Coe, coelom; ec. Ectoderm; eg, external glomerulus; en, endoderm; Ms, mesodermic somite; N, nervous system; n, nephrostome; nc, notochord; pc, prone- phric chamber; Wd, Wolffian duct. — {Modified from Felix.) ing, or nephrostome, an outgrowth of the coelomic epithelium is formed, and a branch from the aorta penetrates into this to form a stalked external glomerulus lying free in the coelomic cavity (Fig. 214, eg). Internal glomeruh, such as occur in connection with the mesonephric tubules do not occur in the pronephros of the human embryo, and this fact, together with the presence of external glomeruli and the participation of the tubules in the formation of the Wolffian duct, serve to distinguish the pronephros from the meson ephros. The pronephric tubules are, as has been stated, transitory struc- tures and by the time the embryo has reached a length of about 5 mm. they have all disappeared. Before their disappearance THE MESONEPHROS 345 Wd is complete, however, a second series of tubules has commenced to develop, forming what is termed the mesonephros or Wolffian^ body. The Development of the Mesonephros. — The pronephric duct does not entirely disappear with the degeneration of the pronephric tubules, but persists to serve as the duct for the meso- nephros and to play an important part in the development of the metanephros also. In the Wolffian ridge there appear in embryos of between 3 and 4 mm. a number of coiled tubules, which arise by some of the cells of the ridge aggregating to form solid cords, at first entirely uncon- nected with either the coelomic epithelium or the Wolffian duct. Later the cords become con- nected with the coelomic epithe- lium and acquire a lumen, and near the coelomic end of the tubule, at a region correspond- ing to the chamber of a prone- phric tubule, a condensation of the mesenchyme of the Wol- ffian ridge occurs to form a glom- erulus into which a branch ex- tends from the neighboring aorta. The tubules finally acquire connection with the Wolffian duct and at the same time lose their connections with the coelomic epithelium, their nephros tomes being accordingly but transitory structures. The tubules rapidly increase in length and become coiled, and the glomeruli project into their cavities, pushing in front of them the wall of the tubule so that it has the appearance represented in Fig. 215. In its anterior portion the Wolffian ridge is formed from distinct intermdiate cell masses, but posterior to the tenth segment it becomes distinguishable from the rest of the mesoderm before this has become segmented, and, failing to undergo transverse division into segments, it forms a continuous column of cells, known as the Fig. 215. — Transverse Section of THE Wolffian Ridge of a Chick Em- bryo OF Three Days. ao, Aorta; gl, glomerulus; gr, genital ridge; mes, mesentery; tnt, mesonephric tubule; vc, cardinal vein; Wd, Wolffian duct. — (Mihalkoricz.) 346 THE MESONEPHROS nephrogenic cord. The anterior tubules of the mesonephros make their appearance in the intermediate cell masses belonging to the sixth cervical segment, its tubules thus overlapping those of the pronephros, and from this level they appear in all succeeding seg- ments and in the nephrogenic cord as far back as the region of the third or fourth lumbar segment, where the cord is partially inter- rupted. This interruption marks the dividing line between the mesonephric and metanephric portions of the cord, the portions posterior to it being destined to give rise to the metanephros. Fig. 216. — Urinogenital Apparatus of a Male Pig Embryo of 6 cm. ao. Aorta; h, bladder; gh, gubernaculum testis; fe, kidney; md, Mullerian duct; sr, suprarenal body; t, testis; w, "Wolffian body; wd, Wolffian duct. — (Mihalkovicz.) But, as is the case with the pronephros, the entire series of meso- nephric tubules is never in existence at any one time, a degenera- tion of the anterior ones supervening even before the posterior ones have differentiated, and the degeneration proceeds to such an extent that in an embryo of about 21 mm. all the tubules of the cervical and thoracic segments have disappeared, only those of the lumbar segments persisting. THE METANEPHROS 347 This does not mean, however, that the number of persisting tubules corresponds with that of the segments in which they occur ,- for the tubules are not segmental in their arrangement, but are much more numerous than such an arrangement would allow. Two, three, or even as many as nine may correspond with the extent of a mesodermic somite and when the reduction is complete in an embryo of 21 mm., where only the tubules corresponding with four or five segments remain, they may number twenty-six in each mesonephros (Felix). This arrangement of the tubules together with the size which they assume when fully developed brings it about that the Wolffian ridges become somewhat volu- minous structures in their mesonephric portions, projecting mark- edly into the coelomic cavity (Fig. 216). Each is attached to the dorsal wall of the body by a distinct mesentery and has in its lateral portion, embedded in its substance, the Wolffian duct, while on its mesial surface anteriorly is the but slightly developed genital ridge (t) . This condition is reached in the human embryo at about the sixth or seventh week of development, and after that period the mesonephros again begins to undergo rapid degenera- tion, so that at about the sixteenth week nothing remains of it except the duct and a few small rudiments whose history will be given later. The Development of the Metanephros. — The first indication of the metanephros or permanent kidney is a tubular outgrowth from the dorsal surface of the Wolffian duct shortly before its entrance into the cloaca (Fig. 172). When first formed this out- growth lies lateral to the posterior portion of the Wolffian ridge, which, as has already been noted (p. 346), is separated from the portion that gives to the mesonephros. This terminal portion of the ridge forms what is termed the metanephric blastema and in embryos of 7 mm. it has come into relation with the outgrowth from the Wolffian duct and covers its free extremity as a cap. Since both the blastema and the outgrowth from the Wolffian duct take part in the formation of the uriniferous tubules, these have a double origin. The outgrowth from the Wolffian duct as it continues to 348 THE METANEPHROS elongate comes to lie dorsal to the mesonephros, carrying the cap of blastema with it, and it soon assumes a somewhat club- shaped form, its terminal enlargement or ampulla forming what may be termed the primary renal pelvis, while the remainder represents the ureter. The primary renal pelvis then becomes bent laterally so that is axis lies at an angle with that of the ureter and it becomes distinctly bilobed (Fig. 217, A) each lobe having a cap of blastema, the original metanephric blastema having divided into two portions. From each lobe there are then pushed out from Fig. 217. — Three reconstructions showing the development of the secondary collecting tubules as branches from the distal end of the ureter in the human em- bryo. The caps of metanephric blastema are not represented. three to six, usually four, outgrowths, (Fig. 217,5) which represent primary collecting tubules, and on their formation the two caps of metanephric blastema undergo divisions into as many parts as there are outgrowths from the lobes, each outgrowth thus having its own cap of blastema. As soon as each primary tubule has reached a certain length its free extremity begins to bud off from two to four secondary collecting tubules, (Fig. 217, C) and a further corresponding division of the metanephric blastema takes place. In their turn these 'secondary tubules similarly bud out tertiary collecting tubules, their development being accompanied by another THE METANEPHROS 349 fragmentation of the blastema and so the process goes on until about the fifth fetal month, the number of generations of collect-.^ ing tubules formed being between eleven and thirteen, each tubule of the final generation having its cap of blastema. In this way there is formed a complicated branching system of tubules, all of which ultimately communicate with the primary renal pelvis and all of which have, in the last analysis, had their Fig, 2 1 8, — Four Stages of Development of a Uriniferous Tubule of a Cat. A, Arched collecting tubule, C, distal convoluted tubule; C, proximal convoluted tubule; H, loop of Henle; M, glomerulus; T, renal vesicle; V, ampulla (drawn from reconstructions prepared by G. C. Huber). origin from the Wolffian duct. They represent, however, only the collecting portions of the uriniferous tubules, their excreting portions having yet to form, and these take their origin from the metanephric blastema. When the terminal collecting tubules have been formed the blastemic cap in connection with each one condenses to form a renal vesicle (Fig. 21S, A, T), which is at first solid, but later be- comes hollow and proceeds to elongate to an S-shaped tubuk, one end of which becomes continuous with the neighboring am- pulla (Fig. 218, B), and in the space enclosed by what/ may be 350 THE METANEPHROS termed the lower loop of the S a collection of mesenchyme cells appears, into which branches penetrate at an early stage from the renal artery to form a glomerulus, the neighboring walls of the tubule becoming exceedingly thin and being transformed into a capsule of Bowman. The upper loop of the S now begins to elongate (Fig. 218, C), growing toward the hilus of the kidney, parallel to the branch of the outgrowth from the Wolffian duct to which it is attached and between this and the glomerulus, and forms a loop of Henle. From the portion of the horizontal limb of the S which lies between the glomerulus and the descending limb of the loop of Henle the proximal convoluted tubule (C) arises, while the distal convoluted and the arched collecting tubules (C and A) are formed from the uppermost portion of the upper loop (Fig. 218, D). The entire length of each uriniferous tubule from Bowman's capsule to the arched collecting tubule inclusive is thus derived from a renal vesicle, that is to say, from the metanephric blastema. Since the tubules of the kidney are formed by the union of two originally distinct structures it is conceivable that[in the cases of certain tubules there may be a failure of the union. The blastemic portions of the tubules would, nevertheless, continue their development and become functional and, since there would be no means of escape for the secretion, the result would be a cystic kidney. Occasionally the two blastemata of opposite sides fuse across the middle line, the re- sult being the formation of a single transverse or horse-shoe shaped kidney or, what is much rarer, the blastema of one side may cross the middle line to fuse with that of the other, the result being an apparently single kidney with two ureters which open normally into the bladder. The primary renal pelvis is the first formed ampulla and does not exactly represent the definitive pelvis. This is produced partly by the enlargement of the primary pelvis and greatly by the enlargement of the collecting tubules of the first four generations, those of the third and fourth generations later being taken up or absorbed into those of the second generation, so that the tubules of the fifth generation appear to open directly into those of the second, which form the calices minores, while those of the first THE MULLERIAN DUCT 35 1 constitute the calices majores. In some kidneys the process of reduction of the earlier formed collecting tubules proceeds a step further, those of the first generation being taken up into the primary renal pelvis, the secondaries then forming a series of short calices arising from a single pelvic cavity. At about the tenth week of development the surface of the human kidney becomes marked by shallow depressions into lobes, of which there are about eighteen, one corresponding to each of the groups of tubules which arise from the same renal vesicle. This lobation persists until after birth and then disappears com- pletely, the surface of the kidney becoming smooth. The Development of the Miillerian Duct and of the Genital Ridge. — At the time when the Wolffian body has almost reached its greatest development the Wolffian ridge is distinctly divided into three portions (Fig. 219), a median or mesonephric portion attached to the body wall, a lateral or tubal portion containing the Wolffian duct and attached to the mesonephric portion, and a genital portion, formed by the genital ridge and also attached to the mesonephric portion, but to its medial surface. In the tubal portion a second longitudinal duct, known as the Miillerian duct (Fig. 219, Md), makes its appearance. Near the anterior end of each Wolffian ridge there is formed on the free edge of the tubal portion an invagination of the peritoneal covering, and by the proliferation of the cells at its tip this invagination gradually extends backward in the substance of the tubal portion and reaches the cloaca in embryos of about 22 mm. The primary peritoneal invagination becomes the abdominal ostium of the Miillerian duct, the backward prolongation forming the duct itself. In Fig. 219 it will be seen that the tubal portion of the left Wolffian ridge is somewhat bent inward toward the median line and in the lower parts of their extent this becomes more pro- nounced in both tubal portions until finally their free edges come in contact and fuse in the median fine, while at the same time their lower edges fuse with the floor of the coelomic cavity. In this way a transverse partition is formed across what will eventually be the pelvis of the adult, this cavity being thus divided into two 352 THE GENITAL RIDGE compartments, a posterior one containing the lower portion of the intestine and an anterior one containing the bladder. With <^^ r-' M N -^ ^i ^ M Fig. 219. — Transverse Section through the Abdominal Region of an Embryo OF 25 MM. Ao, Aorta; B, bladder; 7, intestine; L, liver; M, muscle; Md, Miillerian duct; Isl , spinal cord; Ov, ovary; KA, rectus abdominis; Sg, spinal ganglion; UA, umbilical artery; Ur, ureter; F, vertebra; W, Wolflfian body; WD, Wolffian duct. — (Keibel.) the formation of this transverse fold, which is represented by the broad ligament in the female, the Miillerian ducts of opposite sides THE GENITAL RIDGE . 353 are brought into contact and finally fuse in the lower portions of their course to form an unpaired utero-vaginal canal. Upon the lateral surface of the mesonephric portion of the Wolffian ridge a longitudinal elevation is formed at about this time. It is the inguinal fold and on the union of the transverse fold with the floor of the coelomic cavity it comes into contact and fuses with the lower part of the anterior abdominal wall, just lateral to the lateral border of the rectus abdominis muscle. In the substance of the fold the mesenchyme condenses to form a ligament-Hke cord, the inguinal ligament, whose further history will be considered later on. The genital ridge makes its appearance as a band-Hke thicken- ing of the epithelium covering the mesial surface of the Wolffian ridge (Fig. 211, gr). Later columns of cells grow down from the thickening into the substance of the Wolffian ridge, displacing the mesonephric tubules to a greater or less extent. These columns are composed of two kinds of cells: (i) smaller epithelial cells with a relatively small amount of cytoplasm and (2) large, spherical cells with more abundant and clear cytoplasm known as sex-cells. The growth of the cell-columns down into the substance of the Wolffian body does not take place, however, to an equal extent in all portions of the length of the genital ridge. Indeed, three regions may be recognized in the ridge; an anterior one in which a relatively small number of cell-columns, extending deeply into the stroma, is formed; a middle one in which numerous columns are formed; and a posterior one in which practically none are formed. The first region has been termed the rete region and its cell-columns the rete-cords, the second region the sex-gland region and its columns the sex-cords, and the posterior region is the mesenteric region and plays no part in the actual formation of the ovary or testis. It has been found that in the lower vertebrates and also in mammals (Allen, Rubaschkin) the sex-cells make their appear- ance, not in the epithelium of the genital ridge, but in the endo- derm of the digestive tract. Thence they wander into the mesentery and eventually into the peritoneum covering the mesial 23 354 THE TESTIS surface of the Wolffian ridge and thus into the epithelium of the genital ridge. Fuss has recently obtained evidence that the sex- cells of the human embryo have a similar origin and undergo a similar migration. The various steps in the differentiation of the reproductive organs so far described occur in all embryos, no matter what their future sex may be. The later stages, however, differ according to sex, and consequently it will be necessary to follow the further Fig. 220. — Section through the Testis and the Broad Ligament of the Testis OF an Embryo of 5.5 mm. ep. Epithelium; md, Mullerian duct; mo, mesorchium; re, rete-cords; sc, sex-cords; wd. Wolffian duct. — (Mihalkovicz.) development first of the testis and then of the ovary, the changes that take place in the ducts and other accessory structures being reserved for a special section. The Development of the Testis. — At about the fourth or fifth week there appears in the sex-gland of the genital ridge a struc- ture which serves to characterize the region as a testis. This is a layer of somewhat dense connective tissue which grows in between the epitheHal and stroma layers of the sex-gland region and gradu- ally extends around almost the entire sex-gland to form the tunica albuginea. By its development the sex-cords are separated from the epithelium, which later becomes much flattened and THE TESTIS 355 eventually almost disappears. Shortly after the appearance of the albuginea the sex-cords unite"'to"'form a complicated network and the rete-cords grow backward along the line of attachment of- the testis to the mesonephric portion of the Wolffian ridge, coming to lie in the hilus of the testis (Fig. 220). They then develop a Mc — ep — ^ Mn PJ 5 I I Pig. 221. — ^Longitudinal Section of the Ovary of an Embryo Cat of 9.4 cm. cor. Cortical layer; ep, epoophoron; Mc, medullary cords; Mn, mesonephros ; pf, peritoneal fold containing Fallopian tube; R, rete; T, Fallopian tube. — (Coert, from Buhler.) lumen and send ofif branches which connect with the sex-cord reticulum and they also make connection with the glomerular portions of the tubules belonging to the anterior part of the mesonephros. Since like the sex-cords, they have by this time separated from the epithehum that gave rise to them, they now extend between the sex- cord reticulum and the anterior mesoneph- 356 THE OVARY ric tubules. Certain portions of the sex-cords now begin to break down leaving other portions to form convoluted stems which eventually become the seminiferous tubules, while from the rete- cords are formed the tubuli recti and rete testis, by which the spermatozoa are transmitted to the mesonephric tubules and so to the Wolffian duct (see p. 358). The development of the seminiferous tubules is not, however, completed until puberty. The stems derived from the sex-cords form cylindrical cords, between which He stroma cells and in- terstitial cells derived from the stroma; but until puberty these cords remain solid, a lumen developing only at that period. The cords contain the same forms of cells as were described as occurring in the epithelium of the germinal ridge, and while in the early stages transitional forms seem to occur, in later periods the two varieties of cells are quite distinct, the sex-cells becoming sperma- togonia (see p. 14) and being the mother cells of the spermatozoa, while the remaining epithelial cells perhaps become transformed into the connective-tissue walls of the tubules. ^ The Development of the Ovary. — In the case of the ovary, after the formation of the sex-cords, connective tissue grows in between these and the epithelium, forming a layer equivalent to the tunica albuginea of the testis. It is, however, a much looser tissue than its homologue in the male, and, indeed, does not completely isolate the sex-cords from the epithelium, although the majority of the cords are separated and sink into the deeper portions of the ovary where they form what have been termed the medullary cords. In the meantime the germinal epithelium has continued to bud off cords which unite to form a cortical layer of cells lying below the epithelium and separated from the medullary cords by the tunica albuginea (Fig. 221). Later the cortical layer becomes broken up by the ingrowth of stroma tissue into spherical or cord-like masses, consisting of sex- cells and epithelial cells (Fig. 222). The invasion of the stroma continuing, these spheres or cords {Pfiuger^s cords) become divided into smaller masses, the primary ovarian follicles, each of which consists as a rule of a single sex-cell surrounded by a number of THE OVARY 357 epithelial cells, the whole being enclosed by a zone of condensed stroma tissue, which eventually becomes richly vascularized and forms a theca folliculi (Fig; lo). The epithelial cells in each^ follicle are at first comparatively few in number and closely surround the sex-cell (Fig. 222, f), which is destined to become an ovum, but in certain of the follicles they undergo an increase by mitosis, becoming extremely numerous, and later secrete a fluid, the liquor folliculi, which collects at one side of the follicle and eventually forms a considerable portion of its contents. The follicular cells are differentiated by its appearance into the stratum granulosum, which surrounds the wall of the follicle, and the discus proligerus, in which the ovum is embedded (Fig. 10, dp), and the cells which immediately surround the ovum, becoming cylindrical in shape, give rise to the corona radiata (Fig. 11, cr). A somewhat similar fate is shared by the medullary cords, these also breaking up into a num- ber of follicles, but sooner or later these follicles undergo degeneration so that shortly after birth practically no traces of the cords remain. It must be noted that degeneration of the follicles formed from the cortical layer also takes place even during fetal life and continues to occur throughout the entire periods of growth and functional activity, numerous atretic follicles being found in the ovary at all times. Indeed it would seem that degeneration is the fate of the great majority of the folHcles and sex-cells of the ovary, but few ova coming to maturity during the life-time of any individual. Rete cords developed from the rete portion of the germinal ridge occur in connection with the ovary as well as with the testis and form a rete ovarii (Fig. 221, R). They do not, however, extend Fig. 222. — Section of the Ovary of A Ne^-born Child. a, Ovarial epithelium; b, proximal part of a Pfliiger's cord; c, sex-cell in epithelium; d and e, spherical masses;/, primary follicle; g, blood-vessel. — (From Gegenbaur, after Waldeyer.) 358 THE GENITAL DUCTS SO deeply into the ovary, remaining in the neighborhood of the mesovarium, and they do not become tubular, but resemble closely the medullary cords with which they are serially homologous. They separate from the epithelium and make connections with the glomeruli of the anterior portion of the mesonephros, on the one hand, and on the other with medullary cords, and in later stages show a tendency to break up into primary follicles, which early degenerate and disappear like those of the medullary cords. The Transformation of the Mesonephros and the Ducts. — At one period of development there are present, as representative of the urinogenital apparatus, the Wolffian body (mesonephros) and duct, the Mullerian duct, and the developing ovary or testis. Such a condition forms an indifferent stage from which the de- velopment proceeds in one of two directions according as the genital ridge becomes a testis or an ovary, the Wolffian body in part undergoing degeneration and in part persisting to form organs which for the most part are rudimentary, while in the female the Wolffian duct also degenerates except for certain rudiments and in the male the Mullerian duct behaves similarly. In the Male. — ^It has been seen that the Wolffian body, through the rete cords, enters into very intimate relations with the testis , and it may be regarded as divided into two portions, an upper genital and a lower excretory. In the male the genital portion persists in its entirety, serving as the efferent ducts of the testis, which, beginning in the spaces of the rete testis, already shown to be connected with the capsules of Bowman, open into the upper part of the Wolffian duct and form the globus major of the epidid- ymis. The excretory portion undergoes extensive degeneration, a portion of it persisting as a mass of coiled tubules ending bUndly at both ends, situated near the head of the epidid3rmis and known as the paradidymis or organ of Giraldes, while a single elongated tubule, arising from the portion of the Wolffian duct which forms the globus minor of the epididymis, represents another portion of it and is known as the vas aberrans. The Wolffian duct is retained complete, the portion of it nearest the testis becoming greatly elongated and thrown into numerous THE GENITAL DUCTS 359 coils, forming the body and globus minor of the epididymis, while the remainder of it is converted into the vas deferens and the diictus ejaculatorius. A lateral outpouching of the wall of the duct to form a longitudinal fold appears at about the thirteenth week and gives rise to the vesicula seminalis, the lateral position of the out- growth explaining the adult position of the vesiculae lateral to the vasa deferentia. At about the fourteenth week evaginations ap- pear in the wall of the outgrowth and somewhat later the lower portion of each Wolffian duct enlarges to form the ampulla, the adult structure of the vesicular apparatus being acquired at about the twenty-fifth week (embryos of 220 mm. vertex-breech length). With the MUllerian ducts the case is very different, since they disappear completely throughout the greater part of their course only their upper and lower ends persisting, the former giving rise to a small sac-like body, the sessile hydatid of Morgagni, attached to the upper end of each testis near the epididymis. It has been seen (p. 351) that the lower ends of the MUllerian ducts, in the male as well as the female, fuse to form the utero- vaginal canal, and the lower portion of this also persists to form what is termed the uterus masculinus, although it corresponds to the vagina of the female rather than to the uterus. It is a short cylindrical pouch of varying length, that opens into the urethra at the bottom of a depression known as the utriculus prostaticus {sinus pocularis). The transverse pelvic partition, produced by the union of the two tubal portions of the Wolffian body, is formed in the male embryo, but at an early stage its anterior surface fuses with the posterior surface of the bladder and consequently there is in the male no pelvic compartment equivalent to the vesico-uterine pouch of the female. The male recto-vesical pouch is, however, the homologue of the recto-uterine pouch of the female. The formation of the inguinal ligament on the surface of the mesonephros has been described on p. 353. On the degeneration of the mesonephros the layer of peritoneum that covered it per- sists to form a mesorchium extending from the body wall to the hilus of the testis and the inguinal ligament now comes to have its origin from the lower pole of that organ, whence it extends to 360 THE GENITAL DUCTS the anterior abdominal wall. Owing to the rudimentary nature of the uterus masculinus and the sHght development of its walls the inguinal ligament does not become involved with it, but remains independent and forms the gubernaculum testis of the adult, whose final position is brought about by the descent of the testis into the scrotum (see p. 369). In the Female. — In the female the transverse partition of the pelvis does not fuse with the bladder but remains distinct as the broad ligament. Consequently there is in the female both a vesico-uterine and a recto-uterine pouch. Since the genital ridges form upon the mesial surfaces of the Wolffian ridges and the tubal portions are their lateral portions, when these latter unite to form the broad ligament the ovary will come to lie upon the posterior surface of that structure, projecting into the recto- vesical pouch. On the degeneration of the mesonephros the peri- toneum that covered it becomes a part of the broad ligament, forming that part of it which contains the Fallopian tubes and hence is known as the mesosalpinx, while the lower part of the ligament, on account of its relation to the uterus, is termed the mesometrium. The genital portion of the mesonephros, though never func- tional as ducts in the female, persists as a group of ten to fifteen tubules, situated between the two layers of the broad ligament and in close proximity to the ovary; these consitute what is known as the epoophoron {parovarium or organ of Rosenmuller) . The tubules terminate blindly at the ends nearest the ovary, but at the other extremity, where they are somewhat coiled, they open into a collecting duct which represents the upper end of the Wolffian duct. Near this rudimentary body is another also composed of tubules, representing the remains of the excretory portion of the mesonephros and termed the paroophoron which, however, degen- erates during the early years of extra-uterine life. So far as the mesonephros is concerned, therefore, the persisting rudiments in the female are comparable to those occurring in the male. As regards the ducts, however, the case is different, for in the female it is the Mlillerian ducts which persist, while the Wolffians THE GENITAL DUCTS 361 undergo degeneration, a small portion of their upper ends per- sisting in connection with the epoophora, while their lower ends persist as straight tubules lying at the sides of the vagina and fornP ing what are known as the canals of Gartner. The Miillerian ducts, UM Pig. 223. -Diagrams Illustrating the Transformation of the MtJLLERiAN AND Wolffian Ducts. B, Bladder; C, clitoris; CG, canal of Gartner; CI, cloaca; Eo, epoophoron; Ep, epididymis; F, Fallopian tube; G, genital gland; HE, hydatid of epididymis; HM, hydatid of Morgagni; K, kidney; MD, Miillerian duct; O, ovary; P, penis; Po, paro- ophoron; Pr, prostate gland; R, rectum; T, testis; U, urethra; UM, uterus masculinus; Ur, ureter; US, urogenital sinus; Ut, uterus; V, vulva; Va, vas aberrans; VD, vas deferens; VS, vesicula seminalis; WB, Wolffian body; WD, Wolffian duct. — {Modi- fied from Huxley.) on the other hand, become converted into the Fallopian tubes {tubcB uterince), and in their lower portions into the uterus and vag- ina. From the margins of the openings by which the Miillerian ducts communicate with the coelom projections develop at an 362 THE GENITAL DUCTS early period and give rise to the fimbricB, with the exception of the one connected with the ovary, the fimbria ovarica, which is the persisting upper portion of the original genital ridge. From the utero-vaginal canal the two structures which give it its name are formed, the entire canal being transformed into the mucous mem- brane of the uterus and vagina. Indeed, the lower ends of the Fallopian tubes are also taken up into the uterus, for the conden- sation of mesenchyme that takes place around the mucosa to form the muscular wall of the uterus is so voluminous that it in- cludes not only the utero-vaginal canal but also the adjacent por- tions of the MUllerian ducts. The histological differentiation of the uterus from the vagina begins to manifest itself at about the third month, and during the fourth month the vaginal portion of the duct becomes flattened and the epitheKum lining its lumen fuses so as to completely occlude it and, a little later, there appears at its lower opening a distinct semicircular fold. This is the hymeUj a structure which seems to be represented in the male by the colliculus seminalis. The obliteratron of the lumen of the vagina persists until about the sixth month, when the cavity is re-estabhshed by the breaking down of the central epithelial cells. The extent of the mesenchymal condensation to form the muscularis uteri also produces a modification of the relations of the inguinal ligament in the female. For the ligament becomes for a short portion of its length included in the condensation and thus attached to the upper portion of the uterus. It is conse- quently divided into two portions, one extending from the lower pole of the ovary to the uterus and forming the ligamentum ovarii proprium and the other extending from the uterus to the anterior abdominal wall and forming what is known in the adult as the round ligament of the uterus. The diagram, Fig. 223, illustrates the transformation from the indifferent condition which occurs in the two sexes, and that the homologies of the various parts may be clearly understood they may also be stated in tabular form as on the next page. In addition to the sessile hydatid, a stalked hydatid also occurs in connection with the testis, and a similar structure is attached to the THE BLADDER 363 fimbriated opening of each Fallopian tube. The significance of these structures is uncertain, though it has been suggested that they are per- sisting rudiments of the pronephros. A failure of the development of the various parts just described to be completed in the normal manner leads to various abnormalities in con- nection with the reproductive organs. Thus there may occur a failure in the fusion of the lower portions of the MuUerian ducts, a bihorned or bipartite uterus resulting, or the two ducts may come into contact and their adjacent walls fail to disappear, the result being a median parti- tion separating the vagina or both the vagina and uterus into two compartments. The excessive development of the fold which gives rise to the hymen may lead to a complete closure of the lower opening of the vagina, while, on the other hand, a failure of the Miillerian ducts to fuse may produce a biperf orate hymen. Indifferent Stage Male Female Genital ridge Testis. Gubernaculum ■! Fimbria ovarica. Ovary, Ovarian ligament. Round ligament. f Wolfl&an body Globus major of epididymis. Paradidymis. Vasa aberrantia. Epoophoron. Paroophoron. Wolffian ducts Body and globus minor epididymis. Vasa deferentia. Seminal vesicles. Ejaculatory ducts. of Collecting tubules of epo- ophoron. Canal of Gartner. Miillerian ducts Sessile hyatid. Uterus masculinus. Fallopian tubes. Uterus. Vagina. The Development of the Urinary Bladder and the Urogenital Sinus. — So far the relations of the lower ends of the urinogenital ducts have not been considered in detail, although it has been seen that in the early stages of development the Wolffian and Miillerian ducts open into the sides of the ventral portion of the cloaca; that the ureters communicate with the lower portions of the Wol- ffian ducts; that from the ventral anterior portion of the cloaca the 364 THE BLADDER allantoic duct extends outward into the belly-stalk; and finally (p. 283), that the cloaca becomes divided into a dorsal portion, which forms the lower part of the rectum, and a ventral portion, which is continuous with the allantois and receives the urinogenital ducts (Fig. 224). It is the history of this ventral portion of the cloaca which is now to be considered. It may be regarded as consisting of two portions, an anterior and a posterior, the line of insertion of the urinogenital ducts Fig. 224.— Reconstruction of the Cloacal Region of an Embryo of 14 mm. al, Allantois; b, bladder; gt, genital tubercle; i, intestine; n, spinal cord; nc, notochord; r, rectum; sg, urogenital sinus; ur, ureter; w. Wolffian duct. — (Keibel.) marking the junction of the two. The anterior or upper portion is destined to give rise to the urinary bladder (Fig. 224, b), while the lower one forms what is known for a time as the urogenital sinus (sg). The bladder, when first differentiated, is a tubular structure, whose lumen is continuous with that of the allantois, but after the second month it enlarges to become more sac-like, while the intraembryonic portion of the allantois degenerates to a sohd cord extending from the apex of the bladder to the umbilicus and is known as the urachus. During the enlargement of the bladder the terminal portions of the urinogenital ducts are taken THE BLADDER 365 up into its walls, a process which continues until finally the ureters and Wolffian ducts open into it separately, the ureters opening to the sides of and a Httle anterior to the ducts. This condition is reached in embryos of about 14 mm. (Fig. 224), and in later stages the interval between the two pairs of ducts is increased (Fig. 225), resulting in the formation of a short canal connecting the lower end of the bladder which receives the ureters with the upper end of the urogenital sinus, into which the Wolffian and ^^.. Fig. 225. — Reconstruction of the Cloacal Structures of an Embryo of 25 mm. bl. Bladder; m, Miillerian duct; r, rectum; sg, urogenital sinus; sy, symphysis pubis; u, ureter; ur, urethra; w. Wolffian duct. — (Adapted from Keibel.) Miillerian ducts open. This connecting canal represents the urethra (Fig. 225, ur), or rather the entire urethra of the female and the proximal part of that of the male, since a considerable portion of the latter canal is still undeveloped (see p. 368). From this urethra there are developed, at about the third month, a number of solid outgrowths which represent the tubules of the prostate gland and are developed in both sexes, although they re- main in a somewhat rudimentary ' condition in the female. In the male they give rise to somewhat branched tubular glands and 366 THE UROGENITAL SINUS are arranged in five main groups, a middle group, arising from the floor of the urethra above the entrance of the ejaculatory ducts, a posterior group also from the floor but below the openings of the ejaculatory ducts, two lateral groups from the sides of the urethra and floor of the grooves on either side of the colliculus seminalis, and an anterior group, smaller than the others, from the urethral roof. Each of these groups gives rise to a lobe of the prostate, the posterior lobe becoming more definitely cir- cumscribed than the others owing to the formation of a con- nective-tissue capsule around it. A few scattered outgrowths arise from the floor of the urethra above the middle group, but as a rule these attain only a sHght development. The muscular tissue, so characteristic of the gland in the adult male, is developed from the surrounding mesenchyme at about the end of the fourth month. The bladder is, accordingly, essentially a derivative of the cloaca and its mucous membrane is therefore largely of endodermal origin. Portions of the Wolffian ducts, which are of mesodermal origin, are, however, taken up into the wall of the bladder and form a portion of it. The extent of the portion so formed is indicated by the position of the orifices of the ureters above and of the ejaculatory ducts below, and it corresponds therefore with what is termed the trigonum vesicce together with the floor of the urethra as far as the openings of the ejaculatory ducts. Throughout this region the mucous membrane is of mesodermal origin. The urogenital sinus is in the early stages also tubular in its upper part, though it expands considerably below, where it is closed by the cloacal membrane. This, by the separation of the cloaca into rectum and sinus, has become divided into two por- tions, the more ventral of which closes the sinus and the dorsal the rectum, the interval between them having become considerably thickened to form the perineal body. In embryos of about 17 mm. the urogenital portion of the membrane has broken through, and in later stages the tubular portion of the sinus is gradually taken up into the more expanded lower portion, until finally the entire sinus forms a shallow depression, termed the vestibule, into the upper part of which the urethra opens, while below are the THE EXTERNAL GENITALIA 367 openings of the Wolffian (ejaculatory) ducts in the male or the orifice of the vagina in the female. In embryos of about 3.0 mm. vertex-breech measurement a small evagination is formed on each lateral wall of the sinus; these give rise to the bulbo-vestibular (Bartholin's) glands of the female or the corresponding bulbo- urethral glands (Cowper's) in the male. The Development of the External Genitalia. — At about the fifth week, before the urogenital sinus has opened to the exterior, the mesenchyme on its ventral wall begins to thicken, producing a slight projection to the exterior. This eminence, which is known as the genital tubercle (Fig. 224, gt)^ rapidly increases in size, its Pig. 226. — The External Genitalia of an Embryo of 25 mm. a. Anus; gf, genital fold; gl, glans; gs, genital swelling; p, perineal body. — (Keibel.) extremity becomes somewhat bulbously enlarged (Fig. 226, gl) and a groove, extending to the base of the terminal enlargement, appears upon its vestibular surface, the lips of the groove forming two well-marked genital folds (Fig. 226, gf). At about the tenth week there appears on either side of the tubercle an enlargement termed the genital swelling (Fig. 226, gs), which is due to a thicken- ing of the mesenchyme of the lower part of the ventral abdominal wall in the region where the inguinal ligament is attached, and with the appearance of these structures the indifferent stage of the external genitals is completed. In the female the growth of the genital tubercle proceeds rather slowly and it becomes transformed into the clitoris, the genital folds 368 THE EXTERNAL GENITALIA becoming prolonged to form the labia minora. The genital swell- ings increase in size, their mesenchyme becomes transformed into a mass of adipose and fibrous tissue and they become converted into the labia majora, the interval between them constituting the vulva. In the male the early stages of development are closely similar to those of the female; indeed, it has been well said that the external genitals of the adult female resemble those of the fetal male. In early stages the genital tubercle elongates to form the penis and the integument which covers the proximal part of it grows forward as a fold which encloses the bulbous enlargement or glans and forms the prepuce, whose epithelium fuses with that covering the glans and only separates from it later by a cornifica- tion of the cells along the plane of fusion. The genital folds meet together and fuse, converting the vestibule and the groove upon the vestibular surface of the penis into the terminal portion of the male urethra and bringing it about that the vasa deferentia and the uterus masculinus open upon the floor of that passage. The two genital swellings are at the same time brought closer together, so as to lie between the base of the penis and the perineal body and, eventually, they form the scrotum. The mesenchyme of which they were primarily composed differentiates into the same layers as are found in the wall of the abdomen and a peritoneal pouch is prolonged into them from the abdomen, so that they form sacs Into which the testes descend toward the close of fetal life (p. 370). The homologies of the portions of the reproductive apparatus derived from the cloaca and of the external genitalia in the two sexes may be perceived from the following table. Male Female Urinary bladder. Urinary bladder. Proximal portion of urethra. Urethra. Bulbo-urethral glands. Bulbo-vestibular glands. Urogenital sinus. . . The rest of the urethra. Vestibule. Genital tubercle. . . Penis. Clitoris. Genital folds Prepuce and integument of penis. Labia minora. Genital swellings. . Scrotum, Labia majora THE DESCENT OF THE OVARIES 369 Numerous anomalies, depending upon an inhibition or excess of the development of the parts, may occur in connection with the external genitalia. Should, for instance, the lips of the groove on the vestibu^;^ lar surface of the penis fail to fuse, the penial portion of the urethra remains incomplete, constituting a condition known as hypospadias, a condition which offers a serious bar to the fulfilment of the sexual act. If the hypospadias is complete and there be at the same time an im- perfect development of the penis, as frequently occurs in such cases, the male genitalia closely resemble those of the female and a condi- tion is produced which is usually known as hermaphroditism. It is noteworthy that in such cases there is frequently a somewhat excessive development of the uterus masculinus, and a similar condition may be produced in the female by an excessive development of the clitoris. Such cases, however, which concern only the accessory organs of re- production, are instances of what is more properly termed spurious hermaphroditism, true hermaphroditism being a term which should be reserved for possible cases in which the genital ridges give rise in the same individual to both ova and spermatozoa. Such cases are of exceeding rarity in the human species, although occasionally observed in the lower vertebrates, and the great majority of the examples of hermaphroditism hitherto observed are cases of the spurious variety. The Descent of the Ovaries and Testes. — The positions finally occupied by the ovaries and testes are very different from those which they possess in the earlier stages of development, and this is especially true in the case of the testes. The change of position is partly due to the rate of growth of the inguinal liga- ments being less than that of the abdominal walls, the reproductive organs being thereby drawn downward toward the inguinal regions where the ligaments are attached. The point of attach- ment is beneath the bottom of a slight pouch of peritoneum which projects a short distance into the substance of the genital swellings and is known as the canal of Nuck in the female, and in the male as the vaginal process. In the female a second factor combines with that just men- tioned. The relative shortening of the inguinal ligaments acting alone would draw the ovaries to-ward the inguinal regions, but since they are united to the uterus by the ovarian ligaments move- ment in that direction is prevented and the ovaries come to lie in the recto-uterine compartment of the pelvic cavity. With the testes the case is more complicated, since in addition 24 370 THE DESCENT OF THE TESTES to the relative shortening of the inguinal ligaments there is an elongation of the vaginal processes into the substance of the genital swellings, and it must be remembered that the testes, like the ovaries, are primarily connected with the peritoneum. Three stages may be recognized in the descent of the testes. The first of these depends on the slow rate of elongation of the inguinal ligaments or gubernacula. It lasts until about the fifth month of development, when the testes lie in the inguinal region of the abdomen, but during this month the elongation of the gubernacu- lum becomes more rapid and brings about the second stage, dur- ing which there is a slight ascent of the testes, so that they come Fig. 227. — Diagrams Illustrating the Descent of the Testis. il. Inguinal ligament; m, muscular layer; s, skin and dartos of the scrotum; t, testis; tv, tunica vaginalis; vd, vas deferens; vp, vaginal process of peritoneum. — (After Her twig.) to lie a little higher in the abdomen. This stage is, however, of short duration, and is succeeded by the stage of the final descent, which is characterized by the elongation of the vaginal processes of the peritoneum into the substance of the scrotum (Fig. 227, ^4). Since the gubernaculum is attached to the abdominal wall be- neath this process, and since its growth has again diminished, the testes gradually assume again their inguinal position, and are finally drawn down into the scrotum with the vaginal processes. The condition which is thus acquired persists for some time after birth, the testicles being readily pushed upward into the abdominal cavity along the cavity by which they descended. LITERATURE 371 Later, however, the size of the openings of the vaginal processes into the general peritoneal cavity becomes greatly reduced, so that each process becomes converted into an upper narrow neckT and a lower sac-like cavity (Fig. 227, B), and, still later, the walls of the neck portion fuse and become converted into a solid cord, while the lower portion, wrapping itself around the testis, becomes the tunica vaginalis (tv). By these changes the testes become permanently located in the scrotum. During the descent of the testes the remains of each Wolffian body, the epididymis, and the upper part of each vas deferens together with the spermatic vessels and nerves, are drawn down into the scrotum, and the mesenterial fold in which they were originally contained also practically disappears, becoming converted into a sheath of .con- nective tissue which encloses the vas deferens and the vessels and nerves, binding them together into what is termed the spermatic cord. The mesorchium, which united the testis to the peritoneum enclosing the Wolffian body, does not share in the degeneration of the latter, but persists as a fold extending between the epididymis and the testis and forming the sinus epididymidis. In the text-books of anatomy the spermatic cord is usually described as lying in an inguinal canal which traverses the abdominal walls ob- liquely immediately above Poupart's ligament. So long as the lumen of the neck portion of the vaginal process of peritoneum remains patent there is such a canal, placing the cavity of the tunica vaginalis in communication with the general peritoneal cavity, but the cord does not traverse this canal, but lies outside it in the retroperitoneal connective tissue. When, however, the neck of the vaginal process disappears, a canal no longer exists, although the connective ti^ue which surrounds the spermatic cord and unites it with the tissues of the abdominal walls is less dense than the neighboring tissues, so that the cord may be readily separated from these and thus appear to lie in a canal. LITERATURE B. M. Allen : " The Embryonic Development of the Ovary and Testes in Mammals," Amer. Journ. of Anat., iii, 1904. J. L. Bremer: "Morphology of the Tubules of the Human Testis and Epididymis," Amer. Journ. Anat., xi, 191 1. A. H. Eggerth: "On the anlage of the bulbo-urethral (Cowper's) and major vestib- ular (Bartholin's) glands in the human embryo," Anat. Record, ix, 1915. 372 LITERATURE E. J. Evatt: "A Contribution to the Development of the Prostate in Man," Jotirn. Anat. and Phys., xliii, 1909. E. J. Evatt: "A Contribution to the Development of the Prostate Gland in the Human Female," Journ. Anat. and Phys., xlv, 191 i. W. Felix: "Die Entwichlung der Harn- und Geschlechtsorgane/' in Keibel-Mall Human Embryology, it, 1912. A. Fleischmann: " Morphologische Studien iiber Kloake und Phallus der Amnioten, Morphol. Jahrhuch, xxx, xxxii, und xxxvi, 1902, 1904, 1907. O. Frankl: "Beitrage zur Lehre vom Descensus te%iic\x\ov\im" Sitzimgsher. der kais. Akad. Wissensch. Wien, Math.-Naturwiss. Classe, cix, 1900. A. Fuss: "Ueber die Geschlechtzelle des Menschen und die Saugetiere," Arch. fiir mikrosk. Anat., lxxxi, 191 2. S. P. Gage: "A Three Weeks Human Embryo, with especial reference to the Brain and the Nephric System," Amer. Journ. of Anat., iv, 1905. D. B. Hart: "The Nature and Cause of the Physiological Descent of the Testes," Journ. Anat. and Phys. xliv, 1909. D. B- Hart: "The Physiological Descent of the Ovaries in the Human Foetus," Journ. Anat. and Phys., xliv, 1909. E. Hauch: "Ueber die Anatomie und Entwicklung der Nieren." Anat. Hefte, xxii, 1903. G. C. HuBER : "On the Development and Shape of the Urinif erous Tubules of Certain of the Higher Mammals," Amer. Journ. of Anat., iv, Suppl., 1905. J. Janosik: " Histologisch-embryologische Untersuchungen iiber das Urogenital- system," Sitzungsher. der kais. Akad. Wissensch. Wien, Math.-Naturwiss. Classe, xci, 1887. J. Janosik: "Ueber die Entwicklung der Nachniere bei den Amnioten," Arch, fiir Anat. u. Phys., Anat. Ahth., 1907. J. Janosik: "Entwicklung des Nierenbeckens beim Menschen," Arch, fur mikrosk Anat., LxxiTi, 1911. F. Ketbel: "Zur Entwickelungsgeschichte des menschlichen Urogenital-apparatus," Archiv fiir Anat. und Physiol., Anat. Ahth., 1896. O. S. Lowsley: "The development of the human prostate gland, etc.," Amer. Journ. Anat., xiii, 191 2. J. B. Macallum: "Notes on the Wolffian Body of Higher Mammals," Amer. Journ. tAnat., I, 1902. E. Martin: "Ueber die Anlage der Urniere beim Kaninchen," Archiv fiir Anat. und Physiol., Anat. Ahth., 1888. H. Meyer: "Die Entwickelung der Urnieren beim Menschen," Archiv fiir mikrosk. Anat., xxxvi, 1890. R. Meyer: "Zur Kenntnis des Gartner'schen Ganges besonders in der Vagina und dem Hymen des Menschen," Arch, fiir mikrosk. Anat., lxxiii, 1909. R. Meyer: "Zur Entwicklungsgeschichte und Anatomie des utriculus prostaticus beim Menschen," Arch, fiir mikrosk. Anat., lxxiv, 1909. G. von Mihalkovicz: "Untersuchungen iiber die Entwickelung des Harn- und Geschlechtsapparates der Amnioten," Internat. Monatsschrift fiir Anat. und Physiol., II, 1885. LITERATURE 373 W. Nagel: "Ueber die Entwickelung des Urogenitalsystems des Menschen," Archiv fiir mikros. Anat., xxxrv, 1889. W. Nagel: "Ueber die Entwicklung des Uterus und der Vagina beim Menschen," Archiv fiir mikrosk. Anat., xxxvii, 1891. W. Nagel: "Ueber die Entwickelung der innere und aussere Genitalien beim menschlichen Weibes," Archiv fUr GynakoL, xlv, 1894. G. Pallin: "Beitrag zur Anatomie und Embryologie der Prostata und der Samen- blasen," Arch, fiir Anat. und Physiol. , Anat. Abth., 1901. K. Peter: " Untersuchungen iiber Bau und Entwicklung der Niererl. Die Nieren- kanalchen des Menschen und einiger Saugetiere, Jena, 1909. A. G. Pohlman: "The Development of the Cloaca in Human Embryos," Amer. Joiirn. of Anat., xii, 191 1. W. Rubaschkin: "Ueber die Urgeschlechtszellen bei Saugetiere," Anat. Hefte, xxxEX, 1909. K. E. Schreiner: "Ueber die Entwicklung der Amniotenhiere," Zeit.fiir wissensch. ZooL, Lxxi, 1902. O. Stoerk: "Beitrag zur Kenntnis des Aufbaues der menschlichen Niere," Anat. Hefte, xxm, 1904. J. Tandler: "Ueber Vornieren-Rudimente beim menschliche Embryo," Anat. Hefte, XXVIII, 1905. F. J. Taussig: "The Development of the Hymen," Amer. Journ. Anat., viii, 1908. F. Tourneux: "Sur le developpement et revolution du tubercle genital chez le foetus humain dans les deux sexes," Journ. de VAnat et de Physiol., xxv, 1889. E. M. Watson: "The Development of the Seminal Vesicles in Man," Amer. Journ. Anat., xxrv, 1918. S. Weber: "Zur Entwickelungsgeschichte des uropoetischen Apparates bei Saugern, mit besonderer Beriicksichtigung der Urniere zur Zeit des Auftretens der blei- benden Niere," Morphol. Arbeiten, vii, 1897. CHAPTER XIV THE SUPRARENAL SYSTEM OF ORGANS To the suprarenal system a number of bodies of peculiar struc- ture, probably concerned with internal secretion, may be assigned. In the fishes they fall into two distinct groups, the one contain- ing organs derived from the ccelomic epithelium and known as interrenal organs, and the other consisting of organs derived from the sympathetic nervous system and which, on account of the characteristic affinity they possess for chromium salts, have been termed the chromaffine organs. But in the amphibia and amniote vertebrates, while both the groups are represented by independent organs, yet they also become intimately associated to form the suprarenal bodies, so that, notwithstanding their distinctly dif- ferent origins, it is convenient to consider them together. The Development of the Suprarenal Bodies.^ — The supra- renal bodies make their appearance at an early stage, while the Wolffian bodies are still in a well-developed condition, and they are situated at first to the medial side of the upper ends of these structures (Fig. 216, sr). Their final relation to the metanephros is a secondary event, and is merely a topographic relation, there being no developmental connection between the two structures. In the human embryo they make their appearance at about the beginning of the fourth week of development as a number of proliferations of the ccelomic epithelium, which project into the subjacent mesenchyme, and are situated on either side of the median line between the root of the mesentery and the upper por- tion of the Wolffian body. The various proliferations soon sepa- rate from the epithelium and unite to form two masses situated in the mesenchyme, one on either side of the upper portion of the abdominal aorta. In certain forms, such as the rabbit, the primary proliferations arise from the bottom of depressions of the 374 DEVELOPMENT OF THE SUPRARENAL BODIES 375 coelomic epithelium (Fig. 228), but in the human embryo these depressions do not form. Up to this stage the structure is a pure interrenal organ, but" during the fifth week of development masses of cells, derived from the abdominal portion of the sympathetic nervous system, begin to penetrate into each of the interrenal masses (Fig. 229), and form strands traversing them. At about the ninth or tenth week fatty granules begin to appear in the interrenal cells and somewhat later, about the fourth month, the sympathetic constituents begin to show their chromaffine characteristics. The two tissues, how- ever, remain intermingled for a considerable time, and it is not / wc \x tw" ' ■'o^^' Ao I M re " '"-. c::^.-'^ ■■, A Fig. 228. — Section through a Portion of the Wolffian Ridge of a Rabbit Embryo of 6.5 mm. Ao, Aorta; ns, nephrostome; Sr, suprarenal body; vc, cardinal vein; wc, tubule of Wolffian body; wd. Wolffian duct. — (Aichel.) until a much later period that they become definitely separated, the sympathetic elements gradually concentrating in the center of the compound organ to become its medullary substauce, while the interrenal tissue forms the cortical substance. Indeed, it is not until after birth that the separation of the two tissues and their histological differentiation is complete, occasional masses of inter- renal tissue remaining imbedded in the medullary substance and an immigration of sympathetic cells continuing until at least the tenth year (Wiesel). A great deal of difference of opinion has existed in the past con- cerning the origin of the suprarenal glands. By several authors they have been regarded as derivatives in whole or in part of the excretory apparatus, some tracing their origin to the mesonephros and others even to the pronephros. The fact that in some mammals the cortical 3^6 DEVELOPMENT OF THE SUPRARENAL BODIES (interrenal) cells are formed from the bottom of depressions of the coelomic epithelium seemed to lend support to this view, but it is now- pretty firmly established that the appearances thus presented do not warrant the interpretation placed upon them and that the interrenal tissue is derived from the coelomic epithelium quite independently of the nephric tubules. That the chromaffine tissue is a derivative of the sympathetic nervous system has long been recognized. During the development of the suprarenal glands portions of their tissue may be separated as the result of unequal growth and form what are commonly spoken of as accessory suprarenal glands, although, since they are usually composed solely of cortical sub- stance, the term accessory interrenal bodies would be more ap- S. SB. S.B. Fig. 229. — Section through the Suprarenal Body of an Embryo of 17 mm. A , Aorta; R, interrenal portion; 5, sympathetic nervous system; SB, sympathetic cells. > penetrating the interrenal portion. — (Wiesel.) propriate. They may be formed at different periods of develop- ment and occur in various situations, as for instance, in the vicinity of the kidneys or even actually imbedded in their substance, on the walls of neighboring blood-vessels, in the retroperitoneal tissue below the level of the kidneys, and in connection with the organs of reproduction, in the spermatic cord, epididymis or rete testis of the male and in the broad ligament of the female. It seems probable that the bodies associated with the repro- ductive apparatus are separated from the main mass of interrenal tissue before the immigration of the sympathetic tissue and before DEVELOPMENT OF THE SUPRARENAL BODIES 377 the descent of the ovaries or testes, while those which occur at higher levels are of .later origin, and in some cases may contain some medullary substance, being then true accessory suprarenals- Such bodies are, however, comparatively rare, the great majority of the accessory bodies being composed of interrenal tissue alone. Independent chromaffine organs also occur, among them the intercarotid ganglia and the organs of Zuckerkandl being especially Fig. 230. — Section of a Cell Ball from the Intercarotid Ganglion of Man. be, Blood capillaries; ev, efferent vein; S, connective-tissue septum;'/, trabeculae. — {From Bohm and Davidoff, after Schaper.) deserving of note. It may also be pointed out, however, that the chromaffine cells have the same origin as the cells of the sympa- thetic ganglia and may sometimes fail to separate from the latter so that the sympathetic ganglia and plexuses frequently contain chromafhne cells. The Intercarotid Ganglia. — These structures, which are fre- quently though incorrectly termed carotid glands, are small bodies about 5 mm. in length, which lie usually to the mesial side of the upper ends of the common carotid arteries. They possess a very rich arterial supply and stand in intimate relation with the 378 THE INTERCAROTID GANGLIA branches of an intercarotid sympathetic plexus, and, furthermore, they are characterized by possessing as their specific constituents markedly chromaffine cells, among which are scattered stellate cells resembling the cells of the sympathetic ganglia. They have been found to rise in pig embryos of 44 mm. by the separation of cells from the ganglionic masses scattered through- out the carotid sympathetic plexuses. These cells, which become the chromafhne cells, arrange themselves in round masses termed cell balls, many of which unite to form each ganglion, and in man each cell ball becomes broken up into trabecules by the blood- vessels (Fig. 230) which penetrate its substance, and the individual balls are separated from one another by considerable quantities of connective tissue. Some confusion has existed in the past as to the origin of this structure. The mesial wall of the proximal part of the internal carotid artery becomes considerably thickened during the early stages of development and the thickening is traversed by numerous blood lacunae which communicate with the lumen of the vessel. This condi- tion is perhaps a relic of the branchial capillaries which in the lower gill- breathing vertebrates represent the proximal portion of the internal carotid, and has nothing to do with the formation of the intercarotid ganglion, although it has been believed by some authors (Schaper) that the ganglion was derived from the thickening of the wall of the vessel. The fact that in some animals, such as the rat and the dog, the ganglion stands in relation with the external carotid and receives its blood-supply from that vessel is of importance in this connection. The thickening of the internal carotid disappears in the higher vertebrates almost entirely, but in the Amphibia it persists throughout life, the lumen of the proximal part of the vessel being converted into a fine mesh work by the numerous trabeculae which traverse it. This carotid labyrinth has been termed the carotid gland, a circumstance which has probably assisted in producing confusion as to the real significance of the intercarotid ganglion. The Organs of Zuckerkandl. — In embryos of 14.5 mm. there have been found, in front of the abdominal aorta, closely packed groups of cells which resemble in appearance the cells composing the ganglionated cord, two of these groups, which extend down- ward along the side of the aorta to below the point of origin of the inferior mesenteric artery, being especially distinct. These cell groups give rise to the ganglia of the praevertebral sympathetic THE ORGANS OF ZUCKERKANDL 379 plexuses and also to peculiar bodies which, from their discoverer, may be termed the organs of Zuckerkandl. Each body stands in_ intimate relation with the fibers of the sympathetic plexuses and has a rich blood-supply, resembling in these respects the inter- carotid ganglia, and the resemblance is further increased by the fact that the specific cells of the organ are markedly chromaffine. n.r. I Fig. 231. — Organs of Zuckerkandl from a New-born Child. a. Aorta; ci, inferior vena cava; i.c, common iliac artery; mi, inferior mesenteric artery; n.l and n.r, left and right accessory organs; pi. a, aortic plexus; u, ureter; v.r.s, left renal vein. — {Zuckerkandl.) At birth the bodies situated in the upper portion of the ab- dominal cavity have broken up into small masses, but the two lower ones, mentioned above, are still well defined (Fig. 231). Even these, however, seem to disappear later on and no traces of them have as yet been found in the adult. 380 LITERATURE LITERATURE A. Kohn: "Ueber den Bau und die Entwickelung der sog. Carotisdriise," Archiv fur mikrosk. Anat., lvi, 1900. A. Kohn: "Das chromaffine Gewebe," Ergebn. der Anal, und Entwickelungsgesch., XII, 1902. H. Poll: "Die vergleichende Entwicklungsgeschichte der Nebennierensysteme der Wirbeltiere," Hertwig^s Handb. der vergl. und exper. Entwicklungslehre der Wirbeltiere, iii, 1906. A. SouLiifi: "Recherches sur le developpement des capsules surrenales chez les Vert^bres," Journ. de I' Anat. et de la Physiol., xsxix, 1903. J. Wiesel: "Beitrage zur Anatomie und Entwickelung der menschlichen Neben- niere," Anat. Heft., xtk, 1902. E. Zuckerkandl: "Ueber Nebenorgane des Sympathicus im Retroperitonealraum des Menschen," Verhandl. Anat. Gesellsch., xv, 1901. CHAPTER XV THE DEVELOPMENT OF THE NERVOUS SYSTEM The Histogenesis of the Nervous System. — The entire central nervous system is derived from the cells lining the medullary groove, whose formation and conversion into the medullary canal has already been described (p. 76). When the groove is first formed, the cells lining it are somewhat more columnar in shape than those on either side of it, though like them they are arranged in a single layer; later they increase by mitotic division and ar- range themselves in several layers, so that the ectoderm of the groove becomes very much thicker than that of the general surface of the body. At the same time the cell boundaries, which were originally quite distinct, gradually disappear, the tissue becoming a syncytium. While its tissue is in this condition the lips of the medullary groove unite, and the subsequent differentiation of the canal so formed differs somewhat in different regions, although a fundamental plan may be recognized. This plan is most readily perceived in the region which becomes the spinal cord, and may be described as seen in that region. Throughout the earlier stages, the cells lining the inner wall of the medullary tube are found in active proliferation, some of the cells so produced arranging themselves with their long axes at right angles to the central canal (Fig. 232), while others, whose des- tiny is for the most part not yet determinable and which therefore may be termed indifferent cells, are scattered throughout the syn- cytium. At this stage a transverse section of the medullary tube shows it to be composed of two well-defined zones, an inner one immediately surrounding the central canal and composed of the indifferent cells and the bodies of the inner or ependymal cells ^ and an outer one consisting of branched prolongations of the syncytial cytoplasm. This outer layer is termed the marginal velum (Rand- 381 382 THE HISTOGENESIS OF THE NERVOUS SYSTEM schleier) (Fig. 232, w). The indifferent cells now begin to wander outward to form a definite layer, termed the mantle layer, lying be- tween the marginal velum and the bodies of the ependymal cells (Fig. 233), and when this layer has become well established the cells composing it begin to divide and to differentiate into (i) cells termed neuroblasts, destined to become nerve-cells, and (2) others '?':;''SI' mv y^--;.. cs Fig. 232. — Transverse Section through the Spinal Cord of a Pig Embryo OF 30 MM., THE Upper Part Showing the Appearance Produced by the Silver. Method of Demonstrating the Neuroglia Fibers. a, Ependyma of floor plate; &, boundary between mantle layer and marginal zone; cs, mesenchymal connective- tissue syncytium; ep, ependymal cells; i, ingrowth of connective tissue; m, marginal velum; mm, mantle layer; mv, mantle layer of floor plate; p, pia mater; r, neuroglia fibers. — (Hardesty.) which appear to be supportive in character and are termed neuro- glia cells (Fig. 233, B). The latter are for the most part small and are scattered among the neuroblasts, these, on the other hand, being larger and each early developing a single strong process which grows out into the marginal velum and is known as an axis- cylinder. At a later period the neuroblasts also give rise to other processes, termed dendrites, more slender and shorter than th( THE HISTOGENESIS OF THE NERVOUS SYSTEM 3^3 axis-cylinders, branching repeatedly, and, as a rule, not extending beyond the limits of the mantle layer. In connection with the neuroglia cells peculiar neuroglia fibrils develop very much in the same way as the fibers are formed in mesenchymal connective tissue. That is to say, they are formed from the peripheral portions of the cytoplasm of the neuroglial and ependymal cells. But since these cells are connected to- gether to form a syncytium the fibrils are not confined to the 'O^O Fig. 233. — Diagram showing the Development of the Mantle Layer in the Spinal Cord. The circles, indifferent cells; circles with dots, neuroglia cells; shaded cells, ger- minal cells; circles with cross, germinal cells in mitosis; black cells, nerve-cells. — (Schaper.) territories of the individual cells, but may extend far beyond these, passing in the syncytium from the territory of one neuroglial cell to another, many of those, indeed, arising in connection with the ependymal cells extending throughout the entire thickness of the medullary wall (Fig. 231). The fibrils branch abundantly and form a supportive network extending through all portions of the central nervous system. The axis-cylinder processes of the majority of the neuroblasts on reaching the marginal velum bend upward or downward and, after traversing a greater or less length of the cord, re-enter the 384 THE HISTOGENESIS OF THE NERVOUS SYSTEM mantle layer and terminate by dividing into numerous short branches which come into relation with the dendrites of adjacent neuroblasts. The processes of certain cells situated in the ventral region of the mantle zone pass, however, directly through the marginal velum out into the surrounding tissues and constitute the ventral nerve-roots (Fig. 236). The dorsal nerve-roots have a very different origin. In em- bryos of about 2.5 mm., in which the medullary canal is only partly closed (Fig. 54), the cells which lie along the line of transi- tion between the lips of the groove and the general ectoderm form a distinct ridge readily recognized in sections and termed the neural crest (Fig. 234, A). When the lips of the groove fuse to- gether the cells of the crest unite to form a wedge-shaped mass, completing the closure of the canal (Fig. 234, B) , and later pro- liferate so as to extend outward over the surface of the canal (Fig. 234, C) . Since this proliferation , is most active in the regions of the crest which correspond to the mesodermic somites there is formed a series of cell masses, ar- ranged segmentally and situated in the mesenchyme at the sides of the medullary canal (Fig. 219).. These cell masses represent the dorsal root ganglia, and certain of their constituent cells, which may also be termed neuroblasts, early assume a fusiform shape and send out a process from each extremity. One of these processes, the axis-cylinder, grows in- ard toward the medullary canal and penetrates its marginal velum, and, after a^longer or shorter course in this zone, enters the mantle layer and comes into contact with the dendrites of some of the central neuroblasts. The other process extends peripherally and Fig. 234. — Three Sections through THE Medullary Canal of an Embryo OF 2.5 MM. — (von Lenhossek.) THE HISTOGENESIS OF THE NERVOUS SYSTEM 385 is to be regarded as an extremely elongated dendrite. The pro- cesses from the cells of each ganglion aggregate to form a nerve^ that formed by the axis-cylinders being the posterior root of a spinal nerve, while that formed by the dendrites soon unites with the ventral nerve-root of the corresponding segment to form the main stem of a spinal nerve. There is thus a very important difference in the mode of de- velopment of the two nerve-roots, the axis-cylinders of the ventral roots arising from cells situated in the wall of the medul- FiG. 235. — Cells from the Gasserian Ganglion of a Guinea-pig Embryo. a, Bipolar cell; b and c, transitional stages to d, T-shaped cells. — (van Gehuchten.) lary canal and growing outward (centrifugally) while those of the dorsal root spring from cells situated peripherally and grow inward (centripe tally) toward the medullary canal. In the majority of the dorsal root ganglia the points of origin of the two processes of each bipolar cell gradually approach one another (Fig. 235, b) and eventually come to rise from a common stem, a process of the cell-body, which thus assumes a characteristic T form (Fig. 235, (/). From what has been said it will be seen that each axis-cylinder is an'outgrowth from a single neuroblast and is part of its cell-body, as are also the dendrites. Another view has, however, been advanced to the effect that the nerve fibers first appear as chains of cells and that the axis-cylinders, being differentiated from the cytoplasm of the chains, are really multicellular products. Many difficulties stand in the way of the acceptance of this view and recent observations, both histo- genetic (Cajal) and experimental (Harrison), tend to confirm the 25 386 THE SPINAL CORD unicellular origin of the axis-cylinders. The embryological evidence therefore goes to support the neurone theory^ which regards the entire nervous system as composed of definite units, each of which corre- sponds to a single cell and is termed a neurone. By the development of the axis-cylinders which occupy the meshes of the marginal velum, that zone increases in thickness and comes to consist principally of nerve-fibers, while the cell-bodies of the neurones of the cord are situated in the mantle zone. No such definite distinction of color in the two zones as exists in the adult is, however, noticeable until a late period of development, the medullary sheaths^ which give to the nerve-fibers their white ap- pearance not beginning to appear until the fifth month and continuing to form from that time onward until after birth. The origin of the myelin which composes the medullary sheaths is as yet uncertain, although the more recent observations tend to show that it is picked out from the blood and deposited around the axis-cylinders in some manner not yet understood. Its appearance is of importance as being associated with the beginning of the definite functional activity of the nerve-fibers. In addition to the medullary sheaths the majortiy of the fibers of the peripheral nervous system are provided with primitive sheaths, which are lacking, however, to the fibers of the central system. They are formed ty cells which wander out from the dorsal root-ganglia and are therefore of ectodermal origin. Frog larvae deprived of their neural crests at an early stage of develop- ment produce ventral nerve-fibers altogether destitute of primi- tive sheaths (Harrison) . Various theories have been advanced to account for the formation of the medullary sheaths. It has been held that the myelin is formed at the expense of the outermost portions of the axis-cylinders them- selves (von Kolliker), and on the other hand, it has been regarded as an excretion of the cells which compose the primitive sheaths surrounding the fibers (Ranvier), a theory which is, however, invalidated by the fact that myelin is formed around the fibers of the central nervous system which possess no primitive sheaths. As stated above, the more recent observations (Wlassak) indicate its exogenous origin. It has been seen that the central canal is closed in the mid- dorsal line by a mass of cells derived from the neural crest. These THE SPINAL CORD 387 cells do not take part in the formation of the mantle layer, but become completely converted into ependymal tissue, and the^ same is true of the cells situated in the mid-ventral line of the canal. In these two regions, known as the roof -plate and floor -plate re- spectively, the wall of the canal has a characteristic structure and does not share to any great extent in the increase of thickness which distinguishes the other regions (Fig. 236). In the lateral walls of the canal there is also noticeable a differentiation into two regions, a dorsal one standing in relation to the ingrowing fibers from the dorsal root ganglia and known as the dorsal zone, and a ventral one the ventral zone, similarly related to the ventral nerve- roots. In different regions of the medullary tube these zones, as well as the roof and floor-plates, undergo different degrees of de- velopment, producing peculiarities which may now be considered. The Development of the Spinal Cord.^Even before the lips of the medullary groove have met a marked enlargment of the anterior portion of the canal is noticeable, the region which will become the brain being thus distinguished from the more posterior portion which will be converted into the spinal cord. When the formation of the mesodermic somites is completed, the spinal cord terminates at the level of the last somite, and in this region still retains its connection with the ectoderm of the dorsal surface of the body; but in that portion of the cord which is posterior to the first coccygeal segment the histological differentiation does not proceed beyond the stage when the walls consist of several layers of similar cells, the formation of neuroblasts and nerve-roots ceasing with the segment named. After the fourth month the more differentiated portion elongates at a much slower rate than the surrounding tissues and so appears to recede up the spinal canal, until its termination is opposite the second lumbar vertebra. The less differentiated portion, which retains its connection with the ectoderm until about the fifth month, is, on the other hand, drawn out into a slender filament whose cells degenerate during the sixth month, except in its uppermost part, so that it comes ^ to be represented throughout the greater part of its extent by a thin cord composed of pia mater. This cord is the structure 388 THE SPINAL CORD known in the adult as the filum terminale, and lies in the center of a leash of nerves occupying the lower part of the spinal canal and termed the cauda equina. The existence of the cauda is due to the recession of the cord which necessitates for the lower Itimbar, sacral and coccygeal nerves, a descent through the spinal canal for a greater or less distance, before they can reach the intervertebral foramina through which they make their exit. In the early stages of development the central canal of the cord is quite large and of an elongated oval form, but later it becomes somewhat rhomboidal in shape (Fig. 236, A), the lateral angles marking the boundaries between the dorsal and ventral zones. As development proceeds the sides of the canal in the dorsal region gradually approach one another and eventually fuse, so that this portion of the canal becomes obliterated (Fig. 136, B) and is indi- cated by the dorsal longitudinal fissure in the adult cord, the central canal of which corresponds to the ventral portion only of the embryonic cavity. While this process has been going on both the roof- and the floor-plate have become depressed below the level of the general surface of the cord, and by a continuance of the depression of the floor-plate — a process really due to the en- largement and consequent bulging of the ventral zone — the an- terior median fissure is produced, the difference between its shape and that of the dorsal fissure being due to the difference in its development. The development of the mantle layer proceeds at first more rapidly in the ventral zone than in the dorsal, so that at an early stage (Fig. 236, A) the anterior column of gray matter is much more pronounced, but on the development of the dorsal nerve- roots the formation of neuroblasts in the dorsal zone proceeds apace, resulting in the formation of a dorsal column. A small portion of the zone, situated between the point of entrance of the dorsal nerve-roots and the roof-plate, fails, however, to give rise to neuro- blasts and is entirely converted into ependyma. This represents the iuture funiculus gracilis (fasciculus ofGoll) (Fig. 236, ^,cG) and at the point of entrance of the dorsal roots into the cord a well- marked ovaLbundle of fibers is formed (Fig. 236, A, ob) which, as THE SPINAL CORD 389 development proceeds, creeps dorsally over the surface of the dorsal horn until it meets the lateral surface of the funiculus gracilis, and, its further progress toward the median line being thus impeded, it insinuates itself between that fasciculus and the posterior horn to form the funiculus cuneatus {fasciculus of Burdach) (Fig. 236, B,cB). Fig. 236. — Transverse Sections through the Spinal Cords of Embryos of (A) ABOUT Four and a Half Weeks and (jB) about three Months. cB, funiculus cuneatus; cG, funiculus gracilis; dh, dorsal column; dz, dorsal zone; fp, floor-plate; oh, oval bundle; rp, roof-plate; vh, ventral column; vz, ventral zone, — {His.) Little definite is as yet known concerning the development of the other fasciculi which are recognizable in the adult cord, but it seems certain that the lateral and anterior cerebro-spinal (pyramidal) fasciculi are composed of fibers which grow downward in the meshes of the marginal velum from neuroblasts situated in the cerebral cortex, while the cerebello-spinal (direct cerebellar) fasciculi and the fibers of the ground-bundles have their origin from cells of the mantle layer of the cord. The myelination of the fibers of the spinal cord begins between the fifth and sixth months and appears first in the funiculi cuneati, and about a month later in the funiculi graciles. The myelination of the great motor paths, the lateral and anterior cerebro-spinal fasciculi, is the last to develop, appearing toward the end of the ninth month of fetal life. 390 THE BRAIN my The Development of the Brain. — The enlargement of the anterior portion of the medullary canal does not take place quite uniformly, but is less along two transverse lines than elsewhere, so that the brain region early becomes divided into three primary vesicles which undergo further differentiation as follows. Upon each side of the anterior vesicle an evagination appears and be- comes converted into a club-shaped structure attached to the ventral portion of the vesicle by a pedicle. These evaginations (Fig. 237, op) are known as the optic evaginations, and being concerned in the formation of the eye will be considered in the succeeding chapter. After their for- mation the antero-lateral portions of the vesicle become bulged out into two proturberances (h) which rapidly increase in size and give rise eventu- ally to the two cerebral hemispheres, which form, together with the por- tion of the vesicle which lies between them, what is termed the telence- phalon or fore-brain, the remainder of the vesicle giving rise to what is known as the diencephalon or Hween-brain (Fig. 237, t). The middle vesicle is bodily converted into the mesence- phalon or mid-brain (m), but the posterior vesicle differentiates so that threepartsmay be recognized: (i) a rather narrow portion which immediately succeeds the mid-brain and is termed the isthmus (i) ; (2) a portion whose roof and floor give rise to the cerebellum and pons respectively, and which is termed the metencephalon or hindbrain (mt) ; and (3) a terminal portion which is known as the medulla oblongata, or, to retain a consistent nomenclature, the myelencephalon or after-brain {my). Fig. 237. — Reconstruction of THE Brain of an Embryo of 2.15 MM. h^ Hemisphere; i, isthmus; m, mesencephalon; mf, mid-brain flex- ure; mt, metencephalon; my, my- elencephalon; nf, nape flexure; ol, otic capstile; op, optic evagina- tion; /, diencephalon. — {His.) THE BRAIN 39i From each of these six divisions definite structures arise whose relations to the secondary divisions and to the primary vesicles may be understood from the following table and from the annexed" figure (Fig. 238), which represents a median longitudinal section of the brain of a fetus of three months. 3d Vesicle. Myelencephalon Metencephalon 2nd Vesicle. ist Vesicle. Isthmus Mesencephalon Diencephalon Telencephalon Medulla oblongata (i). / Pons (II i). \ Cerebellum (II 2). (Brachia conjunctiva. Cerebral peduncles (posterior por- tion) (III). {Cerebral peduncles (anterior por- tion) (IV i). Corpora quadrigemina (IV 2). {Pars mammillaris (V i). Thalamus (V 2). Epiphysis (V 3). Infundibulum (VI i). Corpus striatum (VI 2). Olfactory bulb (VI 3). Hemispheres (VI 4). But while the walls of the primary vesicles undergo this com plex differentiation, their cavities retain much more perfectly their original relations, only that of the first sharing to any great extent the modifications of the walls. The cavity of the third vesicle persists in the adult as the fourth ventricle, traversing all the subdivisions of the vesicle; that of the second, increasing but little in height and breadth, constitutes the aqu(Bd7ictus cerebri {iter) ; while that of the first vesicle is continued into the cerebral hemispheres to form the lateral ventricles, the re- mainder of it constituting the third ventricle, which includes the cavity of the median portion of the telencephalon as well as the entire cavity of the diencephalon. During the differentiation of the various divisions of the brain certain flexures appear in the roof and floor, and to a certain ex- 392 THE BRAIN tent correspond with those already described as occurring in the embryo. The first of these flexures to appear occurs in the region of the mid-brain, the first vesicle being bent ventrally until it comes to lie at practically a right angle with the axis of the mid- brain. This may be termed the mid-brain flexure (Fig. 237, mf) and corresponds with the head-bend of the embryo. The second flexure occurs in the region of the medulla oblongata and is known as the nape flexure (Fig. 237, nf)\ it corresponds with the similarly named bend of the embryo and is produced by a bending ventrally of the entire head, so that the axis of the mid-brain comes to lie ]\Z Fig. 238. — Median Longitudinal Section of the Brain of an Embryo of tiiic Third Month. — {His.) almost at right angles with that of the medulla and that of the first vesicle parallel with it. Finally, a third flexure occurs in the region of the metencephalon and is entirely peculiar to the nervous system; it consists of a bending ventrally of the floor of the hind-brain, the roof of this portion of the brain not being affected by it, and it may consequently be known as the pons flexure (Fig. 238). In the later development the pons flexure practically dis- appears, owing to the development in this region of the transverse fibers and nuclei of the pons, but the mid-brain and nape flexures THE MYELENCEPHALON 393 persist, though greatly reduced in acuteness, the axis of the anterior portion of the adult brain being inclined to that of the^ medulla at an angle of about 134 degrees. The Development of the Myelencephalon. — In its posterior portion the myelencephalon closely resembles the spinal cord and has a very similar development. More anteriorly, however, the roof -plate (Fig. 239, rp) widens to form an exceedingly thin mem- brane, the posterior velum; with the broadening of the roof -plate there is associated a broadening of the dorsal portion of the brain cavity, the dorsal and ventral zones bending outward, until, in the anterior portion of the after-brain, the margins of the dorsal zone have a lateral position, and are, indeed, bent ventrally to form a reflected lip (Fig. 239, /). The portion of the fourth ven- tricle contained in this division of the brain becomes thus con- verted into a broad shallow cavity, whose floor is formed by the ventral zones separated in the median line by a deep groove, the floor of which is the somewhat thickened floor-plate. About the fourth month there appears in the roof-plate a transverse groove into which the surrounding mesenchyme dips, and, as the groove deepens in later stages, the mesenchyme contained within it be- comes converted into blood-vessels, forming the chorioid plexus of the fourth ventricle, a structure which, as may be seen from its development, does not lie within the cavity of the ventricle, but is separated from it by the portion of the roof-plate which forms the floor of the groove. In embryos of about 9 mm. the differentiation of the dorsal and ventral zones into ependymal and mantle layers is clearly visible (Fig. 239), and in the ventral zone the marginal velum is also well developed. Where the fibers from the sensory ganglion of the vagus nerve enter the dorsal zone an oval area (Fig. 239, fs) is to be seen which is evidently comparable to the oval bundle of the cord and consequently with the fasciculus of Burdach. It gives rise to the solitary fasciculus of adult anatomy, and in embryos of ii to 13 mm. it becomes covered in by the fusion of the reflected lip of the dorsal zone with the sides of the myelen- cephalon, this fusion, at the same time, drawing the margins of 394 THE MYELENCEPHALON the roof-plate ventrally to form a secondary lip (Fig. 240) . Soon after this a remarkable migration ventrally of neuroblasts of the dorsal zone begins. Increasing rapidly in number the migrating cells pass on either side of the solitary fasciculus toward the territory of the ventral zone, and, passing ventrally to the ventral portion of the mantle layer, into which fibers have penetrated and which becomes the formatio reticularis (Fig. 240, /r), they differentiate to form the olivary body (ol). Fig. 239. — Transverse Section through the Medulla Oblongata of an Embryo of 9.1 mm. dz, Dorsal zone; fp, floor-plate; fs, fasciculus solitarius; I, lip; rp, roof-plate; vz, ventral zone; X and XII, tenth and twelfth nerves. — (His.) The thickening of the floor-plate gives opportunity for fibers to pass across the median line from one side to the other, and this opportunity is taken advantage of at an early stage by the axis- cylinders of the neuroblasts of the ventral zone, and later, on the establishment of the olivary bodies, other fibers, descending from the cerebellum, decussate in this region to pass to the olivary body of the opposite side. In the lower part of the medulla fibers from the neuroblasts of the nuclei gracilis and cuneatus, which seem to be developments from the mantle layer of the dorsal zone^ also decussate in the substance of the floor-plate; these fibers, known as the arcuate fibers, pass in part to the cerebellum, associating themselves with fibers ascending from the spinal cord and with the olivary fibers to form a round bundle situated in the dorsal THE METENCEPHALON AND ISTHMUS 395 portion of the marginal velum and known as the restiform lody (Fig. 240, tr). The principal differentiations of the zones of the myelen- cephalon may be stated in tabular form as follows: Roof -plate Posterior velum. (Nuclei of termination of sensory roots of cranial nerves. Nuclei gracilis and cuneatus. The olivary bodies. ,^ , J Nuclei of origin of the motor roots of cranial nerves. Ventral zones < ^, ^. , , I The reticular formation. Floor-plate The median raphe. Fig. 240. — Transverse Section through the Medulla Oblongata of an Em- bryo OF about Eight Weeks. av. Ascending root of the trigeminus; fr, reticular formation; ol, olivary body; sf, solitary fasciculus; tr, restiform body; XII, hypoglossal nerve. — (His.) The Development of the Metencephalon and Isthmus. — Our knowledge of the development of the metencephalon, isthmus, and mesencephalon is by no means as complete as is that of the myelencephalon. The pons develops as a thickening of the por- tion of the brain floor which forms the anterior wall of the pons flexure, and its transverse fibers are well developed by the fourth month (Mihalkovicz), but all details regarding the origin of the pons nuclei are as yet wanting. If one may argue from what oc- curs in the myelencephalon, it seems probable that the reticular formation of the metencephalon is derived from the ventral zone, and that the median raphe represents the floor-plate. Further- 396 THE CEREBELLUM more, the relations of the pons nuclei to the reticular formation on the one hand, and its connection by means of the transverse pons fibers with the cerebellum on the other, suggest the possibility that they may be the metencephalic representatives of the olivary bodies and are formed by a migration ventrally of neuro- blasts from the dorsal zones, such a migration having been ob- served to occur (Essick). The cerebellum is formed from the dorsal zones and roof-plate of the metencephalon and is a thickening of the tissue imme- diately anterior to the front edge of the posterior velum. This latter structure has in early stages a rhomboidal shape (Fig. 241, Fig. 241. — A, Dorsal View of the Brain of a Rabbit Embryo of 16 mm.; Median Longitudinal Section of a Calf Embryo of 3 cm. c, Cerebellum; m, mid-brain. — (Mihalkovicz.) A) which causes the cerebellar thickening to appear at first as if composed of two lateral portions inclined obliquely toward one another. In reality, however, the thickening extends entirely across the roof of the brain (Fig. 241, B), the roof-plate probably being invaded by cells from the dorsal zones and so giving rise to the vermis, while the lobes are formed directly from the dorsal zones. During the second month a groove appears on the ventral surface of each lobe, marking out an area which becomes the floc- culus, and later, during the third month, transverse furrows appear upon the vermis dividing it into five lobes, and later still extend out upon the lobes and increase in number to produce the lamellate structure characteristic of the cerebellum. The histogenetic development of the cerebellum at first pro- ceeds along the lines which have already been described as typical, THE CEREBELLUM 397 but after the development of the mantle layer the cells lining the greater portion of the cavity of the ventricle cease to multiply, only those which are situated in the roof-plate of the metencepha- lon and along the line of junction of the cerebellar thickening with the roof-plate continuing to divide. The indifferent cells formed in these regions migrate outward from the median line and forward in the marginal velum to form a superficial layer, known as the epithelioid layer ^ and cover the entire surface of cerebellum. (Fig. 242). The cells of this layer, like those of the mantle, differentiate into neuroglia cells and neuro- blasts, the latter for the most part migrating centrally at a later stage to mingle with the cells of the mantle layer and to become transformed into the granular cells of the cere- bellar cortex. The neuroglia cells remain at the surface, however, forming the prin- cipal constituent of the outer or, as it is now termed, the molecular layer of the cortex, and into this the dendrites of the Purkinje cells, probably derived from the mantle layer, pro- ject. The migration of the neuroblasts of the epithelial layer is probably completed before birth, at which time but few remain in the molecular layer to form the stellate cells of the adult. The origin of the dentate and other nuclei of the cerebellum is at present unknown, but it seems probable that they arise from cells of the mantle layer. The nerve-fibers which form the medullary substance of the cerebellum do not make their appearance until about the sixth month, when they are to be found in the ependymal tissue on the inner surface of the layer of granular cells. Those which Fig. 242. — Diagram Representing the Differentiation of the Cerebei^lar Cells, The circles, indifferent cells; circles -with dots, neuroglia cells; shaded cells, germinal cells; circles with cross, germinal cells in mitosis; black cells, nerve-cells. L, Lateral recess; M, median furrow, and R, floor of IV, fourth ventricle. — {Schapef.) 398 THE ISTHMUS are not commissural or associative in function converge to the line of junction of the cerebellum with the pons, and there pass into the marginal velum of the pons, myelencephalon, or isthmus as the case may be. The dorsal surface of the isthmus is at first barely distinguish- able from the cerebellum, but as development proceeds its roof- plate undergoes changes similar to those occurring in the medulla oblongata and becomes converted into the anterior velum. In the dorsal portion of its marginal velum fibers passing to and from the cerebellum appear and form the hrachia conjunctiva, while ventrally fibers, descending from the more anterior portions of the brain, form the cerebral peduncles. Noting is at present known as to the history of the gray matter of this division of the brain, although it may be presumed that its ventral zones take part in the formation of the tegmentum, while from its dorsal zones the nuclei of the brachia conjunctiva are possibly derived. The following table gives the origin of the principal structures of the metencephalon and isthmus : Metencephalon Isthmus Roof-plate. > / Posterior velum. Anterior velum. \ Vermis of cerebellum. f Lobes of cerebellum. Brachia conjunctiva. iFlocculi. Nuclei of termination of sen- sory roots of cranial nerves. ,^ [ Pons nuclei. Nuclei of origin of motor Posterior part of cere- roots of cranial nerves. bral peduncles. Ventral zones 1 Reticular formation. Posterior part of teg- [ mentum. Floor-plate Median raphe. Median raphe. The Development of the Mesencephalon. — Our knowledge of the development of this portion of the brain is again very imperfect. During the stages when the flexures of the brain are well marked (Figs. 237 and 238) it forms a very prominent structure and pos- sesses for a time a capacious cavity. Later, however, it increases THE MESENCEPHALON 399 in size less rapidly than adjacent parts and its wall thicken, the roof- and floor-plates as well as the zones, and, as a result, the cavity becomes the relatively smaller canal-like cerebral aquaeduct. In the marginal velum of its ventral zone fibers appear at about the third month, forming the anterior portion of the cerebral peduncles, and, at the same time, a median longitudinal furrow appears upon the dorsal surface, dividing it into two lateral eleva- tions which, in the fifth month, are divided transversely by a second furrow and are thus converted from corpora bigemina (in which form they are found in the lower vertebrates) into corpora quadrigemina. Nothing is known as to the differentiation of the gray matter of the dorsal and ventral zones of the mid-brain. From the relation of the parts in the adult it seems probable that in addition to the nuclei of ori- gin of the oculomotor and trochlear nerves, the ventral zones give origin to the gray matter of the tegmentum, which is the forward continuation of the reticular formation. Similarly it may be supposed that the cor- pora quadrigemina are developments of the dorsal zones, as may also be the red nuclei, whose relations to the brachia conjunctiva suggest a com- parison with the olivary bodies and the nuclei of the pons. A tentative scheme representing the origin of the mid-brain structures may be stated thus: Roof-plate (?) Dorsal zones f Corpora quadrigemina. \ Red nuclei. Ventral zones J Anterior part of tegmentum. \ Anterior part of cerebral peduncles. Floor-plate Median raphe. The Development of the Diencephalon.—A transverse section through the diencephalon of an embryo of about five weeks (Fig. 243) shows clearly the differentiation of this portion of the brain into the typical zones, the roof-plate (rp) being represented by a thin-walled, somewhat folded area, the floor-plate (fp) by the tissue forming the floor of a well-marked ventral groove, while each lateral wall is divided into a dorsal and ventral zone by a groove known as the sulcus Monroi (Sm), which extends forward and ventrally toward the point of origin of the optic evagination 400 THE DTENCEPHALON (Fig. 245). At the posterior end of the ridge-like elevation which represents the roof-plate is a rounded elevation (Fig. 244, p) which, in later stages, elongates until it almost reaches the dermis, form- ing a hollow evagination of the brain roof known as the pineal process. The distal extremity of this process enlarges to a sac- like structure which later becomes lobed, and, by an active proliferation of the cells lining the cavities of the various lobes, finally becomes a solid structure, the pineal body. The more proximal portion of the evagination, '"'* remaining hollow, forms the pineal stalky and the entire structure, body and stalk, constitutes what is known as the epiphysis. Fig. 243. — Transverse Sec- tion OF THE DiENCEPHALON OF AN Embryo of Five Weeks. dz, dorsal zone;//?, floor-plate; rp, roof-plate; Sm, sulcus Monroi; vz, ventral zone. — {His.) The significance of this organ in the Mammalia is doubtful. In the Reptilia and other lower forms the outgrowth is double, a secondary outgrowth arising from the base or from the anterior wall of the primary one. This anterior evagi- nation elongates until it reaches the dorsal epidermis of the head, and, there expanding, develops into an unpaired eye, the epidermis which overlies it be- coming converted into a transparent cornea. In the Mammaha this anterior process does not develop and the epiphy- sis in these forms is comparable only to the posterior process of the Reptilia. In addition to the epiphysial evaginations, another evagination arises from the roof -plate of the first brain vesicle, further forward, in the region which becomes the median portion of the telencephalon. This para- physis as it has been called, has been observed in the lower vertebrates and in the Marsupials (^Selenka), but up to the present has not been found in other groups of the Mammalia. It seems to be comparable to a chorioid plexus which is e vagina ted from the brain surface instead of being invaginated as is usually the case. There is no evidence that a paraphysis is developed in the human brain. The portion of the roof -plate which lies in front of the epiphysis represents the velum interpositum of the adult brain, and it forms at first a distinct ridge (Fig. 244, rp). At an early stage, however, THE DIENCEPHALON 401. it becomes reduced to a thin membrane upon the surface of which blood-vessels, developing in the surrounding mesenchyme, arrange themselves at about the third month in two longitudinal plexuses, which, with the subjacent portions of the velum, become in- vaginated into the cavity of the third ventricle to form its chorioid plexus. The dorsal zones thicken in their more dorsal and anterior portions to form massive struc- tures, the thalami (Figs. 237, V2, and 244, ot), which, encroaching upon the cavity of the ventricle, transform it into a narrow slit- like space, so narrow, indeed, that at about the fifth month the inner surfaces of the two thalami come in contact in the median line, forming what is known as the intermediate mass. More ven- trally and posteriorly another thickening of the dorsal zone occurs, giving rise on each side to the pulvinar of the thalamus and to a lateral geniculate body, and two ridges extending back- ward and dorsally from the latter structures to the thickenings in the roof of the mid-brain which represent the anterior corpora quadrigemina, give a path along which the nerve-iibers which constitute the superior quadri- geminal brachia pass. From the ventral zones what is known as the hypothalamic region develops, a mass of fibers and cells whose relations and development are not yet clearly understood, but which may be 26 Fig. 224. — Dorsal View of the Brain, the Roof of the Lateral Ventricles being Removed, of an Embryo of 1.36 mm. b, Superior brachium; eg, lateral geniculate body; c/», choroid plexus; cqa, anterior corpus quadrigeminun^; h, hip- pocampus; hf, hippocampal fissure; ot, thalamus; p, pineal body; rp, roof-plate. —(His.) 402 THE TELENCEPHALON regarded as the forward continuation of the tegmentum and reticular formation. In the median line of the floor of the ventricle an unpaired thickening appears, representing the corpora mammil- laria, which during the third month becomes divided by a median furrow into two rounded eminences; but whether these structures and the posterior portion of the tuber cinereum, which also develops from this region of the brain, are derivatives of the ventral zones or of the floor-plate is as yet uncertain. Assuming that the mammillaria and the tuber cinereum are de- rived from the ventral zones, the origins of the structures formed from the walls of the diencephalon may be tabulated as follows: Roof-plate f Velum interpositum. [ Epiphysis. f Thalami. Dorsal zones I Pulvinares. 1 Lateral geniculate bodies. I Hypothalamic region. Ventral zones ^ Corpora mammillaria. [ Tuber cinereum (in part). Floor-plate Tissue of mid- ventral line. The Development of the Telencephalon. — For convenience of description the telencephalon may be regarded as consisting of a median portion, which contains the anterior part of the third ven- tricle, and two lateral outgrowths which constitute the cerebral hemispheres. The roof of the median portion undergoes the same transformation as does the greater portion of that of the dienceph- alon and is converted into the anterior part of the velum inter- positum (Fig. 246, vi). Anteriorly this passes into the anterior wall of the third ventricle, the lamina terminalis (It), a structure which is to be regarded as formed by the union of the dorsal zones of opposite sides, since it lies entirely dorsal to the anterior end of the sulcus Monroi. From the ventral part of the dorsal zones the optic evaginations are formed, a depression, the optic recess (or), marking their point of origin. The ventral zones are but feebly developed, and form the anterior part of the hypothalamic region, while at the anterior extremity of the floor-plate an evagination occurs, the infundibular THE TELENCEPHALON 403 recess {ir), which elongates to form a funnel-shaped structure known as the hypophysis. At its extremity the hypophysis comes in contact during the fifth week with the enlarged extremity of Rathke's pouch formed by an invagination of the roof of the oral sinus (see p. 287), and applies itself closely to the posterior surface of this (Fig. 238), to form with it the pituitary body. The anterior lobe at an early stage separates from the mucous membrane of the oral sinus, the stalk by which it was attached completely dis- appearing, and the posterior wall of the sack so formed wraps itself Pig. 245. — Diagram Showing the Relationships of the Pituitary Body in THE Adult Brain. (Tilney.) cm, corpus mammillare; inf, inf undibulum ; It, lamina terminalis; oc, optic commissure. The infundibulum portion of the pituitary body is represented in solid black, the tuberal portion is stippled and the anterior lobe cross hatched. around the downgrowth from the brain, completely investing it and forming the infundibular portion (Fig. 245) of the pituitary body (Tilney). From the ventral portion of the anterior wall an outgrowth appears on either side, and these, growing upwards aver the lateral surfaces of the sack, push their way between it and the base of the diencephalon, uniting in the middle line and also sending a process backwards to surround the upper part of the 404 THE TELENCEPHALON stalk (infundibulum) connecting the hypophysis with the brain- The plate of pituitary tissue thus formed, resting upon the under surface of that portion of the floor of the diencephalon which becomes the tuber cinereum, gives rise to what is termed the tuheral portion of the pituitary body, (Fig. 245) while the anterior wall of the oval sack, sending out proces- ses into the surrounding mesenchyme and so giving rise to a mass of solid cords of cells embedded in a mesenchyme rich in blood vessels, forms what is termed the anterior lobe or distal portion. The tuberal portion becomes also highly vascular and its cells arrange themselves in cords, which, however possess a lumen in which a colloid secretion collects in later stages; the infundi- bular portion does not become vascularized to any great extent and its cells form a many-layered epithelial investment of the hypophysis, while between it and the distal portion a cleftlike space remains as the representative of the cavity of the original oral sack. The cavity of the hypophysis, which in early stages is quite large, later becomes obliterated except in its proximal portion and the neural downgrowth thus becomes converted into a solid mass composed of neuroglia cells and fibers, among which some colloid material may occasionally be present. The cerebral hemispheres are formed from the lateral portions of the dorsal zones, each possessing also a prolongation of the roof-plate. From the more ventral portion of each dorsal zone there is formed a thickening, the corpus striatum (Figs. 246, cs^ and 238, F/ 2) , a structure which is for the telencephalon what the optic thalamus is for the diencephalon. It is at first anterior to and quite separate from the thalamus (Fig. 243) but later, as it enlarges, it extends backwards so as to overlie the anterior part of the thalamus laterally and fuses with it so that the two gang- lionic masses become continuous, though the area of contact remains indicated by the tcsnia semicircularis. When the pro- jection fibers from the cerebral cortex develop they converge to form a definite band, the internal capsule, the posterior portion of which passes between the thalamus and the corpus striatum, while the anterior portion passes through the substance of the THE TELENCEPHALON 405 striatum, dividing it into two portions, the nucleus caudatus and the nucleus lenticularis , the caudate nucleus, with the growth of the cerebral hemisphere, being prolonged backwards as a slender process almost to the tip of lateral horn of the ventricle. From the dorsal portions of the dorsal zones of the telencephalon the remaining or mantle (pallial) portions of the hemispheres are developed (Figs. 246, h and 238, F14). When first formed, the hemispheres are slight evaginations from the median portion of the telencephalon the openings by which their cavities communi- cate with the third ventricle, the interventricular foramina, being relatively very large (Fig. 246), but, in later stages (Fig. 238), or ir Fig, 246. — Median Longitudinal Section of the Brain of an Embryo of 16.3 MM. hr. Anterior brachium; eg, corpus geniculatum laterale; cs, corpus striatum; IC, cerebral hemisphere; ir, infundibular recess; It, lamina terminalis; or, optic recess; ol, thalamus; p, pineal process; sm, sulcus Monroi; st, hypothalamic region; vi, velum interpositum. — {His.) the hemispheres increase more markedly and eventually surpass all the other portions of the brain in magnitude, overlapping and completely concealing the roof and sides of the diencephalon and mesencephalon and also the anterior surface of the cerebellum. In this enlargement, however, the interventricular foramina share only to a slight extent and consequently become relatively smaller (Fig. 238), forming in the adult merely slit-like openings lying between the lamina terminalis and the thalami and having for their roof the anterior portion of the velum interpositum. 4o6 THE TELENCEPHALON The velum interpositum — that is to say, the roof-plate — where it forms the roof of the interventricular foramen, is pro- longed out upon the dorsal surface of each hemisphere, and, be- coming invaginated, forms upon it a groove. As the hemispheres, increasing in height, develop a mesial wall, the groove, which is the so-called chorioidal fissure^ comes to lie along the ventral edge of this wall, and as the growth of the hemispheres continues it becomes more and more elongated, being carried at first backward (Fig. 247), then ventrally, and finally forward to end at the tip of the temporal lobe. After the estab- lishment of the grooves the mesenchyme in their vicinity dips into them, and, developing blood-vessels, becomes the chorioid plexuses of the lateral ventricles, and at first these plexuses grow much more rapidly than the ventricles, and so fill them almost completely. Later, however, the walls of the hemispheres gain the ascendancy in rapidity of growth and the plexuses become rela- tively much smaller. Since the por- tions of the roof -plate which form the chorioidal fissures are continuous with the velum interpositum in the roofs of the interventricular foramina, the chorioid plexuses of the lateral and third ventricles become continuous also at that point. The mode of growth of the chorioid fissures seems to indicat the mode of growth of the hemispheres. At first the growth more or less equal in all directions, but later it becomes mori extensive posteriorly, there being more room for expansion ii that direction, and when further extension backward become difficult the posterior extremities of the hemispheres bend ventrally toward the base of the cranium, and reaching this, turn for war to form the temporal lobes. As a result the cavities of the hemi- spheres, the lateral ventricles, in addition to being carried forwar to form an anterior horn, are also carried backward and ventrallj Fig. 247. — Median Longi- tudinal Section of the Brain OF AN Embryo Calf of 5 cm. cb, Cerebellum; cp, chorioid plexus; cs, corpus striatum; /M, interventricular foramen; in, hypophysis; in, mid-brain; oc, optic commissure; t, posterior part of the diencephalon. — (Mihalkovicz.) THE CEREBRAL CONVOLUTIONS 407 to form the lateral or descending horn, and the corpus striatum likewise extends backward to the tip of each temporal lobe as a slender process known as the tail of the caudate nucleus. In addition to the anterior and lateral horns, the ventricles of the human brain also possess posterior horns extending backward into the occipital portions of the hemispheres, these portions, on account of the greater persistence of the mid-brain flexure (see p. 392), being enabled to develop to a greater extent than in the lower mammals. The scheme of the origin of parts in the telencephalon may be stated as follows: Median Part Hemisphere P - , ( Anterior part of velum inter- f Floor of chorioidal I positum. \ fissure. positi Dorsal zones | Lamina terminalis. ^ Optic evaginations. Anterior part of hypothalamic Ventral zones \ region. [ Anterior part of tuber cinereum, Pallium. Corpus striatum. Olfactory lobes (see p. 411). The Convolutions of the Hemispheres. — The growth of the hemispheres to form the voluminous structures found in the adult depends mainly upon an increase of size of the pallium. The corpus striatum, although it takes part in the elongation of each hemisphere, nevertheless does not increase in other directions as rapidly and extensively as the pallium, and hence, even in very early stages, a depression appears upon the surface of the hemi- sphere where the corpus is situated (Fig. 248). This depression is the lateral cerebral fossa, and for a considerable period it is the only sign of inequality of growth on the outer surfaces of the hemispheres. Upon the mesial surfaces, however, at about the time that the chorioid fissure appears, another linear depression is formed dorsal to the chorioid, and when fully formed extends from in front of the interventricular foramen to the tip of the temporal lobe (Fig. 250, h). It affects the entire thickness of the pallial wall and consequently produces an elevation upon the inner surface, a projection into the cavity of the ventricle which is known 4o8 THE CEREBRAL CONVOLUTIONS as the hippocampus, whence the fissure may be termed the hip- pocampal fissure. The portion of the pallium which intervenes between this fissure and the chorioidal forms what is known as the dentate gyrus. Toward the end of the third or the beginning of the fourth month two prolongations arise from the fissure just where it turns to be continued into the temporal lobe, and these, extending posteriorly, give rise to the parieto-occipital and calcarine fissures. Like the hippocampal, these fissures produce elevations upon the inner surface of the pallium, that formed by the parieto- occipital early disappearing, while that produced by the calcarine persists to form the calcar (hippocampus minor) of adult anatomy. The three fissures just de- scribed, together with the chorioidal and the lateral cerebral fossa, are all formed by the beginning of the fourth month and all the fissures affect the entire thickness of the wall of the hemisphere, and hence have been termed the primary or total fissures. Unti the beginning of the fifth month they are the only fissures presentj but at that time secondary fissures, which, with one exceptionj are merely furrows of the surface of the pallium, make thei appearance and continue to farm until birth and possibly later Before considering these, however, certain changes which occur ii the neighborhood of the lateral cerebral fossa may be described. The fossa is at first a triangular depression situated above th( temporal lobe on the surface of the hemisphere. During th( fourth month it deepens considerably, so that its upper and lowei margins become more pronounced and form projecting folds, and during the fifth month, these two folds approach one another anc Fig. 248. — Brain of an Embryo of the Fourth Month. c, Cerebellum; p, pons; s, lateral cerebral fossa. THE CEREBRAL CONVOLUTIONS 409 eventually cover in the floor of the fossa completely, the groove which marks the line of their contact forming the lateral cerebral fissure, while the floor of the fossa becomes known as the insula. The first of the secondary fissures to appear is the sulcus cinguli, which is formed about the middle of the fifth month on the mesial surface of the hemispheres, lying parallel to the anterior portion of the hippocampal fissure and dividing the mesial surface into the gyri marginalis snidfornicatus. A little later, at the beginning of the sixth month, several other fissures make their appearance Fig. 249. — Cerebral Hemisphere of an Embryo of about the Seventh Month. fs, Superior frontal sulcus; ip, interparietal; IR, insula; pci, inferior pre-central; pes, superior pre-central; ptc, post-central; R, central; S, lateral; t^, first temporal. — (Cunningham.) upon the outer surface of the pallium, the chief of these being the central sulcus, the inter- parietal, the pre- and post-central, and the temporal sulci, the most ventral of these last running parallel with the lower portion of the hippocampal fissure and differing from the others in forming a ridge on the wall of the ventricle termed the collateral eminence, whence the fissure is known as the collateral. The position of most of these fissures may be seen from Fig. 249, and for a more complete description of them reference may be had to text-books of descriptive anatomy. 4IO THE CORPUS CALLOSUM In later stages numerous tertiary fissures make their appear- ance and mask more or less extensively the secondaries, than which they are, as a rule, much more inconstant in position and shallower. The Corpus Callosum and Fornix. — While these fissures have been forming, important structures have developed in connection with the lamina terminalis. Up to about the fourth month the lamina is thin and of nearly uniform thickness throughout, but at this time it begins to thicken near its dorsal edge and fibers appear in the thickening. These fibers belong to three sets. In the first place, certain of them arise in connection with the olfactory tracts (see p. 412) and from the region of the hippocampal gyrus, which is also associated with the olfactory sense, and, passing through the substance of the lamina terminalis, they extend across the median line to the corresponding regions of the opposite cerebral hemisphere. They are therefore commissural fibers and form what is termed the anterior commissure (Figs. 250, ca and 251, ac). Secondly, fibers, wh^'ch have their origin from the cells of the hippocampus, develop along the chorioidal edge of that structure, forming what is termed the fimbria. They follow along the edge of the chorioidal fissure and, when this reaches the interventricular foramen, they enter as the pillars of the fornix (Figs. 250, cf\ Fig. 256,/) the substance of the lamina terminalis and, passing ventrally in it, eventually reach the hypothalamic region, where they terminate in the corpora mammillaria. Thirdly, as the mantle develops fibers radiate from all parts of it toward the dorsal portion of the lamina terminalis and traversing it are distributed to the corresponding portions of the mantle of the opposite side. These fibers are also commissural in character and form the corpus callosum (Figs. 250 and 251, cc). With the de- velopment of these three sets of fibers and especially those forming the corpus callosum, the dorsal portion of the lamina terminalis becomes enlarged so as to form a triangular area extending between the two cerebral hemispheres (Fig. 251), the corpus callosum form- ing its dorsal portion and base, which is directed anteriorly, the pillars of the fornix its ventral portion, while the anterior com- missure occupies its ventral anterior angle. THE OLFACTORY LOBES 4II The portion of the triangle included between the callosum and the fornix remains thin and forms the septum pellucidum, and a split occurring in the center of this gives rise to the so-called fifth' ventricle, which, from its mode of formation, is a completely closed cavity and is not lined with ependymal tissue of the same nature as that found in the other ventricles. Owing to the very consider- able size reached by the tri- angular area whose history has just been described, important changes are wrought in the adjoining portions of the mesial surface of the hemispheres. Before the development of the area the gyrus dentatus and the hippocampus extend forward into the anterior portion of the hemispheres (Fig. 250), but on account of their position they become encroached upon by the „ ^ •' Fig. 250. — Median Longitudinal enlargement of the corpus cal- Section of the Brain of an Embryo of losum, with the result that the ^°'',!' ^aklrrne fissure; ca, anterior com- hippocampus becomes p r a C- "fissure; u, corpus callosum; c/. chorioidal . fissure; dg, dentate gyrus; jm, interven- tlCally obliterated m that por- tricularforamen;fe,hippocampalfissure;^o, tion of its course which lies in P^^ieto-occipitalfissure.-(M.-;.a/feo..-c2.) the region occupied by the corpus callosum, its fissure in this region becoming known as the callosal fissure, while the corresponding portions of the dentate gyrus become reduced to narrow and insig- nificant bands of nerve tissue which rest upon the upper surface of the corpus callosum and are known as the lateral longitudinal stricB. The Olfactory Lobes. — ^At the time when the cerebral hemi- spheres begin to enlarge — that is to say, at about the fourth week — a slight furrow, which appears on the ventral surface of each ante- riorly, marks off an area which, continuing to enlarge with the hemispheres, gradually becomes constricted off from them to form a distinct lobe-like structure, the olfactory lobe (Fig. 238, 412 HISTOGENESIS OF THE CEREBRAL CORTEX VI 3). In most of the lower mammalia these lobes reach a very considerable size, and consequently have been regarded as con- stituting an additional division of the brain, known as the rhinen- cephalon, but in man they remain smaller, and although they are at first hollow, containing prolongations from the lateral ventricles, the cavities later on disappear and the lobes become solid. Each lobe becomes differentiated into two portions, its terminal portion becoming converted into the club-shaped structure, the olfactory bulb and stalk, while its proximal portion gives rise to the olfactory tracts, the trigone, and the anterior perforated substance. Histogenesis of the Cere- bral Cortex. — In embryos of the sixth week the walls of the cerebral hemispheres present the fundamental structural plan already de- FiG. 251.— Median Longitudinal Sec- scribed (p. 38 1), possessing TION OF THE BRAIN OF AN EmBRYO OF THE , . , Fifth Month. an outer margmal zone, a ac. Anterior commissure; cc, corpus cal- middle mantle ZOnC and an losum; rf|:, dentate gyrus; /.fornix ; j, infundib- . j i 1 - uium; mc, intermediate mass; si, septum mner ependymal or matrix ?,^.w'^,?''^'^f ' "'' "'^^'''^ interpositum.- ^onc. Toward the close {Mthalkovtcz.) of the second month of development there begins a migration of neuroblasts from the mantle and matrix zones toward the surface, and these migrating cells eventually come to rest in the deeper layers of the marginal zone, forming there a well-defined cortical layer. This migration becomes very pronounced during the third month of development and later diminishes, although it seems probable that it is con- tinued in less degree even until after birth (Melius). The neuro- blasts of the cortical layer thus formed differentiate into the pyramidal and other cells of the adult cortex. The outer layers of the marginal zone become the molecular layer, and beneath the cortical layer the axis cylinders passing to and from the THE SPINAL NERVES 413 cortical cells gradually form the white substance of the pallium. The fibers of the white substance do not begin to acquire their myelin sheaths until toward the end of the ninth month and the " process is not completed until some time after birth (Flechsig); while the fibers in the cortex continue to undergo myelination until comparatively late in life (Kaes). The Development of the Spinal Nerves. — It has already been seen that there is a fundamental difference in the mode of development of the two roots of which the typical spinal nerves are composed, the ventral root being formed by axis-cylinders which arise from neuroblasts situated within the substance of the spinal cord, while the dorsal roots arise from the cells of the neural crests, their axis-cylinders growing into the substance of the cord while their dendrites become prolonged peripherally to form the sensory fibers of the nerves. Throughout the thoracic lumbar and sacral regions of the cord the fibers which grow out from the anterior horn cells converge to form a single nerve-root in each segment, but in the cervical region fibers which arise from the more laterally situated neuroblasts make their exit from the cord independently of the more ventral neuroblasts and form the roots of the spinal accessory nerve (see p. 421). In the cervical region there are accordingly three sets of nerve-roots, the dorsal, lateral, and ventral sets. In a typical spinal nerve, such as one of the thoracic series, the dorsal roots as they grow peripherally pass ventrally as well as outward, so that they quickly come into contact with the ventral roots with whose fibers they mingle, and the mixed nerve so formed soon after divides into two trunks, a dorsal one, which is distributed to the dorsal musculature and integument, and a larger ventral one. The ventral division as it continues its outward growth soon reaches the dorsal angle of the pleuro-peritoneal cavity, where it divides, one branch passing into the tissue of the body-wall while the other passes into the splanchnic mesoderm. The former branch, continuing its onward course in the body-wall, again divides, one branch becoming the lateral cutaneous nerve, while the other continues inward to terminate in the median 414 THE CRANIAL KERVES ventral portion of the body as the anterior cutaneous nerve. The splanchnic branch forms a ramus communicans to the sympathetic system and will be considered more fully later on. ^ The conditions just described are those which obtain through- out the greater part of the thoracic region. Elsewhere the fibers of the ventral divisions of the nerves as they grow outward tend to separate from one another and to become associated with the fibers of adjacent nerves, giving rise to plexuses. In the regions where the limbs occur the formation of the plexuses is also asso- ciated with a shifting of the parts to which the nerves are supplied, a factor in plexus formation which is, however, much more evident from comparative anatomical than from embryological studies. The Development of the Cranial Nerves. — During the last thirty years the cranial nerves have received a great deal of atten- tion in connection with the idea that an accurate knowledge of their development would afford a clue to a most vexed problem of vertebrate morphology, the metamerism of the head. That the metamerism which was so pronounced in the trunk should extend into the head was a natural supposition, strengthened by the dis- covery of head-cavities in the lower vertebrates and by the in- dications of metamerism seen in the branchial arches, and the problem which presented itself was the correlation of the various structures belonging to each metamere and the determination of the modifications which they had undergone during the evolution of the head. In the trunk region a nerve forms a conspicuous element of each metamere and is composed, according to what is known as Bell's law, of a ventral or efferent and a dorsal or afferent root. Until comparatively recently the study of the cranial nerves has been dominated by the idea that it was possible to extend the application of Bell's law to them and to recognize in the cranial region a number of nerve pairs serially homologous with the spinal nerves, some of them, however, having lost their afferent roots, while in others a dislocation, as it were, of the two roots had occurred. The results obtained from investigation along this line have THE CRANIAL NERVES 415 not, however, proved entirely satisfactory, and facts have been elucidated which seem to show that it is not possible to extend Bell's law, in its usual form at least, to the cranial nerves. It has been found that it is not sufficient to recognize simply afferent and efferent roots, but these must be analyzed into further com- ponents, and when this is done it is found that in the series of cranial nerves certain components occur which are not represented in the nerves of the spinal series. Before proceeding to a description of these components it will be well to call attention to a matter already alluded to in a pre- : vious chapter (p. 87) in connection with the segmentation of the mesoderm of the head. It has been pointed out that while there exist ''head-cavities" which are serially homologous with the mesodermal somites of the trunk, there has been imposed upon this primary cranial metamerism a secondary metamerism repre- sented by the branchiomeres associated with the branchial arches, and, it may be added, this secondary metamerism has become the more prominent of the two, the primary one, as it developed, gradually slipping into the background until, in the higher verte- brates, it has become to a very considerable extent rudimentary. In accordance with this double metamerism it is necessary to recognize two sets of cranial muscles, one derived from the cranial myotomes and represented by the muscles of the eyeball, and one derived from the branchiomeric mesoderm, and it is necessary also to recognize for these two sets of muscles two sets of motor nerves, so that, with the dorsal or sensory nerve-roots, there are alto- gether three sets of nerve-roots in the cranial region instead of only two, as in the spinal region. These three sets of roots are readily recognizable both in the embryonic and in the adult brain, especially if attention be directed to the cell groups or nuclei with which they are associated (Fig. 252). Thus there can be recognized: (i) a series of nuclei from which nerve-fibers arise, situated in the floor of the fourth ventricle and aquaeduct close to the median line and termed the ventral motor nuclei; (2) a second series of nuclei of origin, situated more laterally and in the substance of the formatio reticularis, and 4l6 THE CRANIAL NERVES known as the lateral motor nuclei; and (3) a series of nuclei in which afferent nerve-fibers terminate, situated still more laterally in the floor of the ventricle and forming the dorsal or sensory nuclei. None of the twelve cranial nerves usually recognized in the text-books contains fibers associated with all three of these nuclei; the fibers from the lateral motor nuclei almost invariably unite with sensory fibers to form a mixed nerve, but those from all Pig. 252. — Transverse Section through the Medulla Oblongata of an Embryo of io mm., showing the Nuclei of Origin of the Vagus (X) and Hypo- glossal (XII) NERVES. — (His.) the ventral motor nuclei form independent roots, while the ol- factory and auditory nerves alone, of all the sensory roots (omit- ting for the present the optic nerve), do not contain fibers from either of the series of motor nuclei. The relations of the various cranial nerves to the nuclei may be seen from the following table, in which the + sign indicates the presence and the — sign the absence of fibers from the nuclear series under which it stands. Two nerves — namely, the second and twelfth — have been omitted from the following table. Of these, the second or optic THE CRANIAL NERVES 417 Number Name Ventral Motor Lateral Motor Sensory I. Olfactory. +^ ~~^ III. Oculomotor. + — — IV. Trochlear. + — — V. Trigeminus. ~" + + VI. Abducens. + — — VII. Facial. — + + VIII. Auditory. - - + IX. Glossopharyngeal. — '+ + X. XL Vagus 1 Spinal Accessory, j - + + L nerve undoubtedly belongs to an entirely different category from the other peripheral nerves, and will be considered in the following chapter in connection with the sense-organ with which it is associated (see especially p. 465). The twelfth or hypoglossal nerve, on the other hand, really belongs to the spinal series and has only secondarily been taken up into the cranial region in the higher vertebrates. It has already been seen (p. 172) that the bodies of four vertebrae are included in the basioccipital bone, and that three of the nerves corresponding to these vertebrae are rep- resented in the adult by the hypoglossal and the fourth by the first cervical or suboccipital nerve. The dorsal roots of the hypo- glossal nerves seem to have almost disappeared, although a ganglion has been observed in embryos of 7 and 10 mm. in the posterior part of the hypoglossal region (His), and probably repre- sents the dorsal root of the most posterior portion of the hypo- glossal nerve. This ganglion disappears, as a rule, in later stages, and it is interesting to note that the ganglion of the suboccipital nerve is also occasionally wanting in the adult condition. An additional nerve, known as the n. terminalis, has been observed both in fetal and adult brains. It is quite small and takes its origin from the region of the olfactory trigone, whence it extends forward, lying medially to the olfactory stalk. It passes through the cribriform plate of the ethmoid and is distributed in the mucous membrane of the nasal septum, ganglion cells occurring along its course. It seems to be quite distinct from the olfactory nerve, but its exact significance is as yet somewhat obscure. 27 41 8 THE CRANIAL NERVES From what has been said it is evident that the hypoglossal roots are to be regarded as equivalent to the ventral roots of the cervical spinal nerves, and the nuclei from which they arise lie in series with the cranial ventral motor roots, a fact which indicates the equivalency of these latter with the fibers which arise from the neuroblasts of the anterior horns of the spinal cord. The equivalents of the lateral motor roots may more conveniently be considered later on, but it may be pointed out here that these are the fibers which are distributed to the muscles of the branchiomeres. In the case of the sensory nerves a further analysis is necessary before their equivalents in the spinal series can be determined. For this the studies which have been made in recent years of the components entering into the cranial nerves of the amphibia (Strong) and fishes (Herrick) must supply a basis, since as yet a direct analysis of the mammalian nerves has not been made. In the forms named it has been found that three different components enter into the formation of the dorsal roots of the cranial nerves: (i) fibers belonging to a general cutaneous or somatic sensory system, distributed to the skin without being connected with any special sense-organs; (2) fibers belonging to what is termed the communis or viscerosensory system, dis- tributed to the walls of the mouth and pharyngeal region and to special organs found in the skin of the same character as those occurring in the mouth; and (3) fibers belonging to a special set of cutaneous sense-organs largely developed in the fishes and known as the organs of the lateral line. The fibers of the somatic sensory system converge to a group of cells, situated in the lateral part of the floor of the fourth ventricle and forming what is termed the trigeminal lobe, and also extend posteriorly in the substance of the medulla (Fig. 253), forming what has been termed the spinal root of the trigeminus and terminating in a column of cells which represents the forward continuation of the posterior horn of the cord. In the fishes and amphibia fibers belonging to this system are to be found in the fifth, seventh, and tenth nerves, but in the mammalia their dis- tribution has apparently become more limited, being confined THE CRANIAL NERVES 419 almost exclusively to the trigeminus, of whose sensory divisions they form a very considerable part. Since the cells around which the fibers of the spinal root of the trigeminus terminate are the forward continuations of the posterior horn of the cord, it seems probable that the fibers of this system are the cranial representa- tives of the posterior roots of the spinal nerves, which, it may be noted, are also somatic in their distribution. The fibers of the viscero-sensory system are found in the lower forms principally in the ninth and tenth nerves (see Fig. 250), nx Pig. 253. — Diagrams showing the Sensory Components of the Cranial Nerves OF A Fish (Menidia). The somatic sensory system is unshaded, the viscero-sensory is cross-hatched, and the lateral line system is black, asc.v. Spinal root of trigeminus; brx, branchial branches of vagus; Ix, lobus vagi; ol, olfactory bulb; op, optic nerve; rc.x, cutaneous branch of the vagus; rix, intestinal branch of vagus; rl, lateral line nerve; rl.acc, accessory lateral line nerve; ros, superficial ophthalmic; rp, ramus palatinus of the facial; thy, hyomandibular branch of the facial; t.inf, infraorbital nerve. — {Herrick.) although groups of them are also incorporated in the seventh and fifth. They converge to a mass of cells, known as the lobus vagi, and like the first set are also continued down the medulla to form a tract known as the fasciculus solitarius or fasciculus communis. In the mammalia the system is represented by the sensory fibers 420 THE CRANIAL NERVES of the glosso-pharyngeo-vagus set of nerves, of which it repre- sents practically the entire mass; by the sensory fibers of the facial arising from the geniculate ganglion and included in the chorda tympani and probably also the great superficial petrosal; and also, probably, by the lingual branch of the trigeminus. Further- more, since the mucous membrane of the palate is supplied by branches from the trigeminus which pass by way of the spheno- palatine (Meckel's) ganglion, and the same region is supplied in lower forms by a palatine branch from the facial, it seems prob- able that the palatine nerves of the mammalia are also to be as- signed to this system.* If this be the case, a very evident clue is afforded to the homologies of the system in the spinal nerves, for since the spheno-palatine ganglion is to be regarded as part of the sympathetic system, the sensory fibers which pass from the viscera to the spinal cord by way of the sympathetic system (p. 425) present relations practically identical with those of the palatine nerves. Finally, with regard to the system of the lateral line, there seems but little doubt that it has no representation whatsoever in the spinal nerves. It is associated with a peculiar system of cutaneous sense-organs found only in aquatic or marine animals, and also with the auditory and possibly the olfactory organs, the former of which are certainly and the latter possibly primarily parts of the lateral line system of organs. The organs are prin- cipally confined to the head, although they also extend upon the trunk, where they are followed by a branch from the vagus nerve, the entire system being accordingly supplied by cranial nerves. In the fishes, in which the development of the organs is at a maximum, fibers belonging to the system are found in all the branchiomeric nerves and all converge to a portion of the medulla known as the tuberculum acusticum. In the Mammalia, with the * The fact that the palatine branches are associated with the trigeminus in the Mammalia and with the facial in the Amphibia is readily explained by the fact that in the latter the Gasserian and geniculate ganglia are not always separated, so that it is possible for fibers originating from the compound ganglion to pass into either THE CRANIAL NERVES 421 disappearance of the lateral line organs there has been a dis- appearance of the associated nerves, and the only certain repre- sentative of the system which persists is the auditory nerve. The table given on p. 417 may now be expanded as follows, though it must be recognized that such an analysis of the mam- malian nerves is merely a deduction from what has been observed in lower forms, and may require some modifications when the components have been subjected to actual observations: Nerve Ventral Motor Lateral Motor Somatic Sensory Visceral Sensory Lateral Line I. __ + III. 4- — - - — IV. + — — — — V. — + + + — VI + — — — — VII. — + — + — VIII. — — — — + IX. ^ X. - + + + - XI. ] XII. + — — — — Spinal. + (?) + + — An additional word is necessary concerning the spinal accessory nerve, for it presents certain interesting relations which possibly furnish a clue to the spinal equivalents of the lateral motor roots. In the first place, neuroblasts which give rise to those fibers of the nerve which come from the spinal cord are situated in the dorsal part of the ventral zones. As the nuclei of origin are traced anteriorly they will be found to change their position somewhat as the medulla is reached and eventually come to lie in the reticular formation, the most anterior of them being practically continuous with the motor nucleus of the vagus. Indeed, it seems that the spinal accessory nerve is properly to be regarded as an extension of the vagus downward into the cervical region (Fiirbringer, Streeter), a process which reaches its greatest development in 422 THE CRANIAL NERVES the mammalia and seems to stand in relation to the development of those portions of the trapezius and sterno-mastoid muscles which are supplied by the spinal accessory nerve. It is believed that the white rami communicantes which pass from the spinal cord to the thoracic and upper lumbar sym- pathetic ganglia arise from cells situated in the dorso-lateral por- tions of the ventral horns, and it is noteworthy that white rami are wanting in the region in which the spinal accessory nerve occurs. Since this nerve represents a cranial lateral motor root the temptation is great to regard the cranial lateral motor roots as equivalent to the white rami of the cord, and this temptation is intensified when it is recalled that there are both embryological and topographical reasons for regarding the branchiomeric muscles, to which the cranial lateral motor nerves are supplied, as equivalent to the visceral muscles of the trunk. But in view of the fact that a sympathetic neurone is always interposed between a white ramus fiber and the visceral musculature (see Fig. 255), while the lateral motor fibers connect directly with the branchio- meric musculature, it seems advisable to await further studies before yielding to the temptation. As regards the actual development of the cranial nerves, they follow the general law which obtains for the spinal nerves, the motor fibers being outgrowths from neuroblasts situated in the walls of the neural tube, while the sensory nerves are outgrowths from the cells of ganglia situated without the tube. In the lower vertebrates a series of thickenings, known as the supr abranchial placodes, are developed from the ectoderm along a line correspond- ing with the level of the auditory invagination, while on a line corresponding with the upper extremities of the branchial clefts another series occurs which has been termed that of the epi- branchial placodes, and with both of these sets of placodes the cranial nerves are in connection. In the human embryo epi- branchial placodes have been found in connection with the fifth, seventh, ninth and tenth nerves, to whose ganglia they contribute cells. The suprabranchial placodes, which in the lower verte- brates are associated with the lateral line nerves, are unrepresented THE SYMPATHETIC SYSTEM 423 in man, unless, as has been maintained, the sense-organs of the internal ear are their representatives. From what has been said above it is clear that the usual arrangement of the cranial nerves in twelve pairs does not represent their true relation- ships with one another. The various pairs are serially homologous neither with one another nor with the typical spinal nerves, nor can they be regarded as representing twelve cranial segments. Indeed, it would seem that comparatively little information with regard to the number of myotomic segments which have fused together to form the head is to be derived from the cranial nerves, for while there are only four of these nerves which are associated with structures equivalent to the meso- dermic somites of the trunk, a much greater number of head cavities or mesodermic somites has been observed in the cranial region of the embryos of the lower vertebrates, Dohrn, for instance, having found nine- teen and Killian eighteen in the cranial region of Torpedo. Further- more, it is not possible to say at present whether the branchiomeres and their associated nerves correspond with one or several of the cranial mesodermic somites, or whether, indeed, any correspondence whatever exists. In early stages of development a series of constrictions have been observed in the cranial portion of the neural tube and have been re- garded as indicating a primitive segmentation of that structure. The neuromeres, as the intervals between successive constrictions have been termed, seem to correspond with the cranial nerves as usually recog- nized and hence cannot be regarded as primitive segmental structures. They are more probably secondary and due to the arrangement of the neuroblasts corresponding to the various nerves. The Development of the Sympathetic Nervous System.— From the embryological standpoint the distinction which has been generally recognized between the sympathetic and central nervous systems does not exist, the former having been found to be an outgrowth from the latter. This mode of origin has been observed with especial clearness in the embryos of some of the lower verte- brates, in which masses of cells have been seen to separate from the posterior root ganglia to form the ganglia of the ganglionated cord (Fig. 254). In the mammalia, including man, the relations cf the two sets of ganglia to one another is by no means so apparent, since the sympathetic cells, instead of being separated from the posterior root ganglion en masse, migrate from it singly or in groups, and are therefore less readily distinguishable from the surrounding meso- dermal tissues. 4^4 THE SYMPATHETIC SYSTEM Flc 254. — ^TlLAJBmESK Smliiuw through an Embkto Shark: (Scynimm) of 1$ mm. imumtmM tbb Okksdt or a Syxpathstk Ganglion. Ck, IfotodMvd; £, ectoderm; G, portenor root gang1if>n; G5. sympathetic gangHon; Jf . spmal cord. — (CHwrfi.) THE SYMPATHETIC STSTEM 425 To nndrrtfand the devdfapmtat ai liie sywpathrtic sytUat, it must be remembered that it conssts typkaDj ai tkree sets ol glia. Oneof thcseiscoastitatcdbytheguigjlEioftkej cord (Fig. 255, GC), the secood is icpnscBted by die gweH» ^ tibe pr2ef\-eTtebrai plezoses (FVG), sodi as Ae caardiac^ adku, l^fpogas- trie, and pehic, wliile die tldni or pcr^iicral set (jPG) is formed bj the cells wiiidi occur thiooj^iOBt the tiwHry of piobafalsr most of the >isccral organs^ cfther m small gnmps or scattered thro«g|b plexuses such as the Auerbach and MeBsacr plenwes of tibe intestine. Each cell in these Tarioas gmefia stands in direct I contact with the axis-cyiinder of a nervous system, probably in the lateral ham of die the corrc^pooding ic^omoi the brai% so that each terminal link of a chain whose hist fink is a m the central system (Huber). Thuifhiml die lumbar regions of the body the central tinct cords known as the vkUe wmad ni^j . which pass from die spinal nerrcs to dK the gangtinnatcd oord^ some of them terminating aionnd Ae of these ganelia, others passing oa to the cds of the praevertchial 426 THE SYMPATHETIC SYSTEM ganglia, and others to those of the peripheral plexuses. In the cervical, lower lumbar and sacral regions white rami are wanting, the central neurones in the first-named region probably making their way to the s>Tnpathetic cells by way of the upper thoracic nerves, while in the lower regions they may pass down the gan- glionated cord from higher regions or may join the praevertebral Pig. 256. — Transverse Sectiok through the Spinal Cord of an Embryo of 7 MM. c, Notochord; g, posterior root ganglion; m, spinal cord; s, sympathetic cell migrating from the posterior root ganglion; wr, white ramus. — {His.) and peripheral ganglia directly without passing through the proxi- mal ganglia. In addition to these white rami, what are known as gray rami also extend between the proximal ganglia and the spinal nerves; these are composed of fibers, arising from sympathetic cells which join the spinal nerves in order to pass with them to their ultimate distribution. The brief description here given applies especially to the sym- pathetic system of the neck and trunk. Representatives of the THE SYMPATHETIC SYSTEM 427 system are also found in the head, in the form of a series of ganglia connected with the trigeminal and facial nerves and known as the ciliary, spheno-palatine, otic, and submaxillary ganglia f and, as will be seen later, there are probably some sympathetic cells which owe their origin to the root ganglia of the vagus and glossopharyngeal nerves. There is nothing, however, in the head region corresponding to the longitudinal bundles of fibers which unite the various proximal ganglia of the trunk to form the ganglionated cord. The first distinct indications of the sympathetic system are to be seen in a human embryo of about 7 mm. As the spinal nerves reach the level of the dorsal edge of the body-cavity, they branch, one of the branches continuing ventrally in the body- wall while the other (Fig. 256, ur) passes mesially toward the aorta, some of its fibers reaching that structure, while others bend so as to assume a longitudinal direction. These mesial branches repre- sent the white rami communicantes, but as yet no ganglion cells can be seen in their course. The cells of the posterior root ganglia have already, for the most part, assumed their bipolar form, but among them there may still be found a number of cells in the neuroblast condition, and these (Fig. 256, 5), wandering out from the ganglia, give rise to a column of cells standing in relation to the white rami. At first there is no indication of a segmental arrangement of the cells of the column (Fig. 257), but at about the seventh week such an arrangement makes its appearance in the cerv'ical region, and later, extends posteriorly, until the column assumes the form of the ganglionated cord. This origin of the ganglionated cord from cells migrating out from the posterior root ganglia has been described by various authors, but recently the origin of the cells has been carried a step further back, to the mantle layer of the central nervous system (Kuntz). Indifferent cells and neuroblasts are said to wander out from the walls of the medullary canal by way of both the posterior and anterior roots and it is claimed that these are the cells that give rise to the ganglionated cord in the manner just described. 428 THE SYMPATHETIC SYSTEM Before, however, the segmentation of the ganglionated cord becomes marked, thickenings appear at certain regions of the cell column, and from these, bundles of fibers may be seen extending Pig. 257. — Reconstruction of the Sympathetic System of an Embryo of 10.2 MM. am, Vitdline artery; ao, aorta; au, umbilical artery; bg, ganglionic mass repre- senting the i>dvic plexus; d. intestine; o€, oesophagus; pc. ganglia of the coeliac plexus; ph, pharynx; rv, right vagus nerve; sp, splanchnic nerves; sy, ganglionated cord; t, trachea;* peripheral sympathetic ganglia in the walls of the stomach. — {His, Jr.) ventrally toward the viscera. The thickenings represent certain of the praevertebral ganglia, and later cells wander out from them and take position in front of the aorta. In an embryo of 10.2 THE SYMPATHETIC SYSTEM 429 mm. two ganglionic masses -(Fig. 257, pc) occur in the vicinity of the origin of the vitelline artery (am), one lying above and the other below that vessel; these masses represent the ganglia oT the coeliac plexus and have separated somewhat from the gang- lionated cord, the fiber bundles which unite the upper mass with the cord representing the greater and lesser splanchnic nerves (sp), while that connected with the lower mass represents the connection of the cord with the superior mesenteric ganglion. Lower down, in the neighborhood of the umbilical arteries, is another enlargement of the cord (bg), which probably represents the inferior mesenteric and hypogastric ganglia which have not yet separated from the cell column. With the peripheral ganglia the conditions are slightly dif- ferent, in that they are formed ver>' largely, if not exclusively, from cells that migrate from the walls of the hind-brain by way of the vagus nerves (Fig. 257). In this way the ganglia of the myenteric, pulmonary and cardiac plexuses are formed, though in the case of the last named it is probable that contributions are also received from the ganglionated cord. The elongated courses of the cardiac sympathetic and splanchnic nerves in the adult receive an explanation from the recession of the heart and diaphragm (see pp. 240 and 325), the latter process forcing down- ward the coeliac plexus, which originally occupied a position opposite the region of the ganglionated cord from which the splanchnic nerves arise. As regards the cephalic s}'mpathetic ganglia, the observations of Remak on the chick and Kolliker on the rabbit show that the ciliar>', sphenopalatine, and otic ganglia arise by the separation of cells from the semilunar (Gasserian) ganglion, and from their adult relations it may be supposed that the cells of the submaxillary and sublingual ganglia have similarly arisen from the geniculate ganglion of the facial nerve. Evidence has also been obtained from human embr}'os that s>inpathetic cells are derived from the ganglia of the vagus and glossophar>'ngeal ner\'es, but, instead of forming distinct ganglia in the adult, these, in all probability, associate themselves with the first cervical ganglia of the gang- lionated cord. 43 O ^^^^ LITERATURE LITERATURE P. Bailey: "Morphology of the roof-plate of the Forebrain and the Lateral Choroid Plexuses in the Human Embryo," Journ. Comp. Neurol., xxvi, 1916. C. R. Bardeen: "The Growth and Histogenesis of the Cerebrospinal Nerves in Mammals," Amer. Jour. Anat., n, 1903. S. R. Cajal: "Nouvelles Observations sur revolution des neuroblasts avec quelques remarques sur I'hypothese neurogenetique de Hensen-Held," Anat. Anzeiger, xxxn, 1908. A. F. Dixon: "On the Development of the Branches of the Fifth Cranial Nerve in Man," Scient. Trans. Roy. Dublin Soc, Ser. i, vi, 1896. C. R. Essick: "The Development of the Nuclei pontis and the Nucleus Arcuatus in Man," Amer. Journ. Anat., xin, 1912. E. GiGLio-Tos: "Sugli organi branchiali e laterali di senso nell' uomo nei primordi del suo sviluppo," Monit. Zool. Ital., xin, 1902. E. GiGLio-Tos: "SulP origine embrionale del nervo trigemino nell' uomo," Anat. Anzeiger, xxi, 1902. E. GiGLio-Tos: "Sul primordi dello sviluppo del nervo acustico-faciale nell' uomo," Anat. Anzeiger, xxi, 1902. K. Goldstein: Die erste Entwicklung der grossen Hirncommissuren und die 'Verwachsung' von Thalamus und Striatum" Archiv fiir Anat. und Physiol., Anat. Abth., 1903. G. Groenberg: "Die Ontogenese einer niederen Saugergehirns nach Untersuch- ungen an Erinaceus europaeus," Zoolog. Jahrb. f. Anat. und Ontogen, xv, 1901. 1. Hardesty: "On the Development and Nature of the Neuroglia," Amer. Journ. Anat., Ill, 1904. R. G. Harrison: " Further Experiments on the Development of Peripheral Nerves," Amer. Journ. of Anat., v, 1906. W. His: "Zur Geschichte des menschlichen Ruckenmarkes und der Nervenwurzeln," Abhandl. der k'dnigl. Sdchsischen Gesellsch., Math.-Physik. Classe, xiii, 1886. W. His: "Zur Geschichte des Gehirns sowie der centralen und peripherischen Ner- venbahnen beim menschlichen Embryo," Abhandl. der Konigl. Sdchsischen Gesellsch., Math.-Physik. Classe, xiv, 1888. W. His: "Die Formentwickelung des menschlichen Vorderhirns vom Ende des ersten bis zum Beginn des dritten Monats," Abhandl. der k'dnigl. Sdchsischen Gesellsch., Math.-Physik. Classe, xv, 1889. W. His: "Histogenese und Zusammenhang der Nervenelemente," Archiv fiir Anat. und Physiol., Anat. Abth., Supplement, 1890. W. His: "Die Entwickelung des menschlichen Gehirns wahrend der ersten Monate," Leipzig, 1904. W. His, Jr. : " Die Entwickelung des Herznervensystem bei Wirbelthieren," Abhandl. der konigl. Sdchsischen Gesellsch., Math.-Physik. Classe, xviii, 1893. W. His, Jr: "Ueber die Entwickelung des Bauchsympathicus beim Hiihnchen und Menschen," Archiv fur Anat. und Physiol., Anat. Abth., Supplement, 1897. C. J. Herrick: "The Cranial and First Spinal Nerves of Menidia: A Contribution upon the Nerve Components of the Bony Fishes," Journ. of Comp. Neurol., DC, 1899. LITERATURE 43 1 C. J. Herrick: "The Cranial Nerves and Cutaneous Sense-organs of the North American Siluroid Fishes," Journ. of Comp. Neurol., xi, 1901. C. H. Heuser: "The Development of the Cerebral Ventricles in the Pig," Amet^ Journ. AnaL, xv, 1913. F. Hochstetter: "Ueber die Entwickelung der Plexus chorioidei der Seitenkam- mern des menschlichen Gehirns," Anat. Anzeiger, xlv, 1913. G. C. Huber: "Four Lectures on the Sympathetic Nervous System," Journ. of Comp. Neurol., vii, 1897. J. B. Johnston: "The Nervus Terminalis in Man and Mammals," Anat. Record, VIII, 1914. A. KuNTz: "A Contribution to the Histogenesis of the Sympathetic System," Anat. Record, in, 1909. A. KuNTz: "The rdle of the Vagi in the Development of the Sympathetic Nervous System," Anat. Anzeiger, xxxv, 1909. A. KuNTz: "The Development of the Sympathetic Nervous System in Mammals," Journ. Compar. Neurol., xx, 19 10. A. KuNTz: "The Development of the Cranial Sympathetic Ganglia in the Pig," Journ. Comp. Neurol., xxiii, 19 13. M. VON Lenhossek: "Die Entwickelung der Ganglienanlagen bei dem menschlichen Embryo," Archiv fur Anat. und Physiol., Anat. Ahth., 1891. F. Marchand: "Ueber die Entwickelung des Balkens im menschlichen Gehirn," Archiv fUr mikrosk. Anat., xxxvu, iSgi. E. L. Mellus: "The Development of the Cerebral Cortex," Amer. Journ. AnaL, xrv, 1912. V. VON Mihalkovicz: " Entwickelungsgeschichte des Gehirns," Leipzig, 1877. A. D. Onodi: "Ueber die Entwickelung des sympathischen Nervensystems," Archiv. fur mikrosk. Anat., xxvn, 1886. C. W. Prentiss: "The Development of the Hypoglossal Ganglia of Pig Embryos," Journ. Comp. Neurol., xx, 1910. G. Retzius: "Das Menschenhirn," Stockholm, 1896. A. Schaper: "Die friihesten Differenzirungsvorgange im Cenlralnervensystem," Archiv fur Entwicklungsmechanik, v, 1897. G. L. Streeter: "The Development of the Cranial and Spinal Nerves in the Occipital Region of the Human Embryo," Amer. Journ. Anat., iv, 1904. G. L. Streeter: "Factors involved in the formation of theFilum terminale," Amer. Journ. Anat., xxv, 19 19. O. Strong: "The Cranial Nerves of Amphibia," Journ. of Morphology, x, 1895. F. Tilney: "An Analysis of the Juxta-neural Epithelial portion of the Hypophysis Cerebri, with an Embryological and Histological Account of a Hitherto Unde- scribed Part of the Organ," Internal. Monastschr. Anat. and Physiol., xxx, 1914- R. Wlassak: "Die Herkunft des Myelins," Archiv fUr Entwicklungsmechanik, vi, 1898. E. Zuckerkandl: "Zur Entwicklung des Balkens," Arbeiten aus neural. Inst. Wien. xvii, 1909. CHAPTER XVI THE DEVELOPMENT OF THE ORGANS OF SPECIAL SENSE Like the cells of the central nervous system, the sensory cells are all of ectodermal origin, and in lower animals, such as the earth-worm, for instance, they retain their original position in the ectodermal epithelium throughout life. In the vertebrates, how- ever, the majority of the sensory cells relinquish their superficial position and sink more or less deeply into the subjacent tissues, being represented by the posterior root ganglion cells and by the sensory cells of the special sense-organs, and it is only in the ol- factory organ that the original condition is retained. Those cells which have withdrawn from the surface receive stimuli only through overlying cells, and in certain cases these transmitting cells are not specially differentiated, the terminal branches of the sensory dendrites ending among ordinary epithelial cells or in such structures as the Pacinian bodies or the end-bulbs of Krause situated beneath undifferentiated epithelium. In other cases, however, certain specially modified superficial cells serve to trans- mit the stimuli to the peripheral sensory neurones, forming such structures as the hair-cells of the auditory epithelium or the gustatory cells of the taste-buds. Thus three degrees of differentiation of the special sensory cells may be recognized and a classification of the sense-organs may be made upon this basis. One organ, however, the eye, cannot be brought into such a classification, since its sensory cells present certain developmental pecularities which distinguish them from those of all other sense-organs. Embryologically the retina is a portion of the central nervous system and not a peripheral organ, and hence it will be convenient to arrange the other sense-organs 432 THE OLFACTORY ORGANS 433 according to the classification indicated and to discuss the history of the eye at the close of the chapter. The Development of the Olfactory Organs. — The general development of the nasal fossa, the epithelium of which contains the olfactory sense cells, has already been described (pp. 102 and 285), as has also the development of the olfactory lobes of the brain (p. 411) , and there remain for consideration here merely the formation of the olfactory nerve and the development of the rudimentary organ of Jacobson. The Olfactory Nerve. — Very diverse results have been obtained by various observers of the development of the olfactory nerve, it having been held at different times that it was formed by the outgrowth of fibers from the olfactory lobes (Marshall), from fibers which arise partly from the olfactory lobes and partly from the olfactory epithelium (Beard), from the cells of an olfactory ganglion originally derived from the olfactory epithelium but later separating from it (His), and finally, that it was composed of the prolongations of certain cells situated and, for the most part at least, remaining permanently in the olfactory epithelium (Disse). The most recent observations on the structure of the olfactory epithelium and nerve indicate a greater amount of probability in the last result than in the others, and the description which follows will be based upon the observations of His, modified in conformity with the results obtained by Disse from chick embryos. In human embryos of the fourth week the cells lining the upper part of the olfactory pits show a distinction into ordinary epithelial and sensory cells, the latter, when fully formed, being elongated cells prolonged peripherally into a short but narrow process which reaches the surface of the epithelium and proximally gives rise to an axis-cylinder process which extends up toward and penetrates the tip of the olfactory lobe to come into contact with the dendrites of the first central neurones of the olfactory tract (Fig. 258). These cells constitute a neuro-epithelium and in later stages of development retain their epithelial position for the most part, a few of them, however, withdrawing into the sub- jacent mesenchyme and becoming bipolar, their peripheral pro- 28 434 THE OLFACTORY ORGANS longations ending freely among the cells of the olfactory epithelium . These bipolar cells resemble closely in form and relations the cells of the embryonic posterior root ganglia, and thus form an interest- ing transition between these and the neuro-epithelial cells. The Organ of Jacob son. — In embryos of three or four months a small pouch-like invagination of the epithelium covering the Fig. 258. — Diagram Illustrating the Relations of the Fibers of the Ol- factory Nerve. Ep, Epithelium of the olfactory pit; C, cribiform plate of the ethmoid, G, glomerulus of the olfactory bulb; M, mitral cell. — {Van Gehuchten.) lower anterior portion of the median septum of the nose can readily be seen. This becomes converted into a slender pouch, 3 to 5 mm. long, ending blindly at its posterior extremity and opening at its other end into the nasal cavity. Its lining epithelium re- sembles that of the respiratory portion of the nasal cavity, and I I THE ORGANS OF TASTE 435 there is developed in the connective tissue beneath its floor a slender plate of cartilage, distinct from that forming the septum of the nose. This organ, which may apparently undergo degeneration in the adult, and in some cases completely disappears, appears to be the representative of what is known as Jacobson's organ, a structure which reaches a much more extensive degree of develop- ment in many of the lower mammals, and in these contains in its epithelium sensory cells whose axis-cylinder processes pass with those of the olfactory sense cells to the olfactory bulbs. In man, however, it seems to be a rudimentary organ, and no satisfactory explanation of its function has as yet been advanced. The olfactory neuro- epithelium, considered from a comparative standpoint, seems to have been derived from the system of lateral line organs so highly developed in the lower vertebrates (Kupffer). In higher forms the system, which is cutaneous in character, has disappeared, except in two regions where it has become highly specialized. In one of these regions it has given rise to the ol- factory sense cells and in the other to the sim'ilar cells of the auditory apparatus. The Organs of Touch and Taste. — ^Little is yet known con- cerning the development of the various forms of tactile organs which belong to the second class of sensory organs described above. The Organs of Taste. — The remaining organs of special sense belong to the third class, and of these the organs of taste present in many respects the simplest condition. They are developed principally in connection with the vallate and foliate papillae of the tongue, and of the former one of the earliest observed stages has been found in embryos of 9 cm. in the form of two ridges of epidermis, lying toward the back part of the tongue and inclined to one another in such a manner as to form a V with the apex di- rected backward. From these ridges solid downgrowths of epi- dermis into the subjacent tissue occur, each downgrowth having the form of a hollow truncated cone with its basal edge continuous with the superficial epidermis (Fig. 259, A). In later stages cylindrical outgrowths develop from the deeper edges of the cone, 436 THE INTERNAL EAR and about the same time clefts appear in the substance of the original downgrowths (Fig. 259, B), and, uniting together, finally open to the surface, forming a trench surrounding a papilla (Fig. 259, C). The outgrowths, which are at first solid, also undergo an axial degeneration and become converted into the glands of Ebner (b), which open into the trench at or near its floor. The various papillae which occur in the adult do not develop simul- taneously, but their number increases with the age of the fetus, and there is, moreover, considerable variation in the time of their development. The taste-buds are formed by a differentiation of the epithe- lium which covers the papillae, and this differentiation appears to stand in intimate relation with the penetration of fibers of the glossopharyngeal nerve into the papillae. The buds form at Pig. 259. — Diagrams Representing the Development of a Vallate Papilla. a. Valley surrounding the papilla; b, von Ebner's gland. — (Graberg.) various places upon the papillae, and at one period are especially abundant upon their free surfaces, but in the later weeks of in- trauterine life these surface buds undergo degeneration and only those upon the sides of the trench persist, as a rule. The foliate papillae do not seem to be developed until some time after the circumvallate, being entirely wanting in embryos of four and a half and five months, although plainly recognizable at the seventh month. The Development of the Ear.— It is customary to describe the mammalian ear as consisting of three parts, known as the inner, middle, and outer ears, and this division is, to a certain extent at least, confirmed by the embryonic development. The inner ear, which is the sensory portion proper, is an ectodermal structure, which secondarily becomes deeply seated in the mesodermal tissue THE INTERNAL EAR 437 of the head, while the middle and outer ears, which provide the apparatus necessary for the conduction of the sound-waves to the inner ear, are modified portions of the anterior branchial arches. It will be convenient, accordingly, in the description of the ear, to accept the usually recognized divisions and to consider first of all the development of the inner ear, or, as it is better termed, the otocyst. The Development of the Otocyst. — In an embryo of 2.4 mm. a pair of pits occur upon the surface of the body about opposite the middle portion of the hind-brain (Fig. 260, A). The ectoderm lining the pits is somewhat thicker than is the neighboring ecto- derm of the surface of the body, and, from analogy with what A '^ B Fig. 260. — Transverse Section Passing through the Otocyst (o/) of Embryos OF {A) 2.4 MM. AND {B) 4 MM. — {His.) occurs in other vertebrates, it seems probable that the pits are formed by the invagination of localized thickenings of the ecto- derm. The mouth of each pit gradually becomes smaller, until finally the invagination is converted into a closed sac (Fig. 260, B)^ which separates from the surface ectoderm and becomes enclosed within the subjacent mesoderm. This sac is the otocyst, and in the stage just described, found in embryos of 4 mm., it has an oval or more or less spherical form. Soon, however, in embryos of 6.9 mm., a prolongation arises from its dorsal portion and the sac assumes the form shown in Fig. 261, A; this prolongation, which is held by some authors to be the remains of the stalk which origi- nally connected the otocyst sac with the surface ectoderm, repre- sents the ductus endolymphaticus , and, increasing in length, it soon becomes a strong club-shaped process, projecting considerably 438 THE INTERNAL EAR beyond the remaining portions of the otocyst (Fig. 261, B). In embryos of about 10.2 mm. the sac begins to show certain other irregularities of shape (Fig. 261, B, sc). Thus, about opposite the point of origin of the ductus endolymphaticus three folds make their appearance, representing the semicircular ducts, and as they increase in size the opposite walls of the central portion of each fold come together, fuse, and finally become absorbed, leaving rsc Pig. 261. — Reconstruction of the Otocysts of Embryos of (A) 6.9 mm. and (B) 10.2 MM. de. Endolymphatic duct; gc, ganglion cochleare; gg, ganglion geniculatum; gv, ganglion vestibulare; sc, lateral semicircular duct. — (His, Jr.) the free edge of the fold as a crescentic canal, at one end of which an enlargement appears to form the ampulla. The transforma- tion of the folds into canals takes place somewhat earlier in the cases of the two vertical than in that of the horizontal duct, as may be seen from Fig. 262, which represents the condition occur- ring in an embryo of 13.5 mm. A short distance below the level at which the canals communi- cate with the remaining portion of the otocyst a constriction ap- THE INTERNAL EAR 439 pears, indicating a separation of the otocyst into a more dorsal portion and a more ventral one. Later, the latter begins to be prolonged into a flattened canal which, as it elongates, becomes coiled up^n itself and also becomes separated by a constriction from the remaining portion of the otocyst (Fig. 263). This canal is the ductus cohlearis (scala media of the cochlea), and the remaining portion of the otocyst subsequently becomes divided by a constriction into the utriculus, with which the semicircular ducts are connected, and the sacculus. The constriction which separates the cochlear duct from the sacculus be- comes the ductus reuniens, while that between the utriculus and sacculus is converted into a narrow canal with which the ductus endolymphaticus connects, and hence it is that, in the adult, the connection between these two portions of the otocyst seems to be formed by the ductus dividing proximally into two limbs, one of which is connected with the utricle and the other with the saccule. When first observed in the human embryo the auditory ganglion is closely associated with the geniculate ganglion of the seventh nerve (Fig. 261, B), the two, usually spoken of as the acustico-facialis ganglion, forming a mass of cells lying in close contact with the anterior wall of' the otocyst. The origin of the ganglionic mass has not yet been traced in the mammalia, but it has been observed that in cow embryos the geniculate ganglion is connected with the ectoderm at the dorsal end of the first branchial cleft (Froriep) , and it may perhaps be regarded as one of the epibranchial placodes Pig. 262. — Reconstruction OF THE Otocyst of an Embryo OF 13.5 MM. CO, Cochlea; de, endolymphatic duct; sc, semicircular duct. — (His, Jr.) 440 THE INTERNAL EAR (see p. 422), and in the lower vertebrates a union of the ganglion with a suprabranchial placode has been observed (Kupffer), this union indicating the origin of the auditory ganglion from one or more of the ganglia of the lateral line system. ^ At an early stage in the human embryo the auditory ganglion shows indications of a division into two portions, a more dorsal one, which represents the future ganglion vestibulare, and a ventral one, the ganglion cochleare. The ganglion cells become bipolar, in which condition they remain throughout life never reaching the de CO ASds Fig. 263. — Reconstruction of the Otocyst of an Embryo of 20 mm., Front View. cc. Common limb of superior and posterior semicircular ducts; eg, cochlear ganglion; co, cochlea; de, endolymphatic duct; s, sacculus; sdl, sdp, and sds, lateral, posterior and superior semicircular ducts; u, utriculus; vg, vestibular ganglion. — iStreeter.) T-shaped condition found in most of the other peripheral cerebro- spinal ganglia. One of the prolongations of each cell is directed centrally to form a fiber of the auditory nerve, while the other penetrates the wall of the otocyst to enter into relations with certain specially modified cells which differentiate from its lining epithelium. In the earliest stages the ectodermal lining of the otocyst is formed of similar columnar cells, but later over the greater part THE INTERNAL EAR 441 of the surface the cells flatten down, only a few, aggregated to- gether to form patches, retaining the high columnar form and de^ veloping hair-like processes upon their free surfaces. These are the sensory cells of the ear. In the human ear there are in all six patches of these sensory cells, an elongated patch (crista ampul- laris) in the ampulla of each semicircular canal, a round patch {macula acustica), in the utriculus and another in the sacculus, and, finally, an elongated patch which extends the entire length of ^■%.;,-^'^m n.^:Y ] J' ^ '" c'' Fig. 264. — Section of the Cochlear Duct of a Rabbit Embryo of 55 mm. a, Mesenchyme; b, to e, epithelium of cochlear duct; M.t, membrana tectoria; V.s.p, vein; i to 7, spiral organ of Corti. — (Baginsky.) the scala media of the cochlea and forms the sensory cells of the spiral organ of Corti. The cells of this last patch are connected with the fibers from the cochlear ganglion, while those of the vestibular ganglion pass to the cristae and maculae. In connection with the spiral organ certain adjacent cells also retain their columnar form and undergo various modifications, giving rise to a rather complicated structure whose development has been traced in the rabbit and bat. Along the whole length of the cochlear duct the cells resting upon that half of the basilar 442 THE INTERNAL EAR membrane which is nearest the axis of the cochlea, and may be termed the inner half, retain their columnar shape, forming two ridges projecting slightly into the cavity of the scala (Fig. 264). The cells of the inner ridge, much the larger of the two, give rise to the memhrana tectoria, as a cuticular secretion to which the cells of the outer ridge also contribute. These latter are arranged in six longitudinal rows (Fig. 264, 1-6); those of the innermost row (i) develop hairs upon their free surfaces and form the inner Ductus semicirc. lat. Precartilage ??etlculum PiG. 265. — Section through the Lateral Semicircular Canal of a Human Embryo of 50 mm. — {Slreeier.) hair cells, those of the next two rows (2 and 3) gradually become transformed on their adjacent surfaces into chitinous substance and form the rods of Corti, while the three outer rows (4 to 6) develop into the outer hair cells. It is in connection with the hair cells that the peripheral prolongations of the cells of the cochlear ganglion terminate, and since these hair cells are ar- ranged in rows extending the entire length of the cochlear duct, the ganglion also is drawn out into a spiral following the coils of the cochlea, and hence is sometimes termed the spiral ganglion. THH INTERNAL EAR 443 While the various changes described above have been taking place in the otocyst, the mesenchyme surrounding it has also been undergoing modification. At first this tissue undergoes a conden- sation around the otocyst and this condensed tissue later assumes the character of pre-cartilage and eventually of cartilage, this rep- resenting the cartilaginous stage of the petrous portion of the temporal bone. The transformation of the mesenchyme into cartilage takes place in embryos of from 25 to 30 mm. in length and at this stage the cartilage is in close contact with the walls of the otocyst. In later stages (Fig. 265), however, the cartilage in the immediate neighborhood of the otocyst undergoes a reversal of development, returning to the precartilage condition and then becoming a syncytial reticulum, and eventually the meshes of the reticulum run together, form cavities of greater or less extent surrounding the various portions of the otocyst and separating them from contact with the surrounding cartilage. The first of these periotic space to form makes its appearance in the region where the stapes is in contact with the otic capsule and it gradually extends so as to enclose the utriculus and sac- culus, forming what is termed the vestibular perilymphatic space. From this the formation of spaces extends into the reticu- lum around each of the semicircular canals, strands of the reticu- lum persisting, however, and imperfectly dividing the space associated with each canal. The reticulum associated with the cochlear duct becomes divided into two portions by the duct forming a broad attachment along its convex surface to the peri- chondrium of the otic capsule and a narrow one along its concave surface to the edge of a shelf-like process of cartilage which later ossifies to form the lamina spiralis (Fig. 266). Above and below these lines of attachment spaces appear in the reticulum, gradu- ally extending along the entire length of the cochlear duct until they communicate at its apex. The upper space so formed com- municates proximally with the vestibular space and forms what is known as the scala vestibuli, while the lower one terminates bhndly at its proximal end, at a point where chondrification and ossification of the otic capsule have failed to occur, producing what 444 THE MIDDLE EAR in the macerated skull appears to be an opening in the petrous bone, the fenestra cochlecB (rotunda). The opening is in reality closed by a thin membrane which separates the proximal end of the lower space from the tympanic cavity, whence the space is known as the scala tympani; the scala media is the cavity of the cochlear duct. A second opening, the fenestra vestibuli (ovalis), also closed by membrane in which the foot of the stapes is em- bedded, occurs in the osseous otic capsule opposite the utriculus and separates the vestibular space from the tympanic cavity. Fig. 266. — Diagrammatic Transverse Section through a Coil of the Cochlea SHOWING the Relation of the Scal/E. c, Organ of Corti; co, ganglion cochleare; Is, lamina spiralis; SM, cochlear duct; ST, scala tympani; SV, scala vestibuli. — (From Gerlach.) The Development of the Middle Ear. — The middle ear develops from the upper part of the pharyngeal groove which represents the endodermal portion of the first branchial cleft. This be- comes prolonged dorsally and at its dorsal end enlarges to form the tympanic cavity, while the narrower portion intervening be- tween this and the pharyngeal cavity represents the tuba auditiva (Eustachian tube). To correctly understand the development of the tympanic cavity it is necessary to recall the structures which form its bound- THE MIDDLE EAR 445 aries. Anteriorly to the upper end of the first branchial pouch there is the upper end of the first arch, and behind it the corre- sponding part of the second arch, the two fusing together dorsal to the tympanic cavity and forming its roof. Internally the cavity is bounded by the outer wall of the cartilaginous investment of the otocyst, while externally it is separated from the upper part of the ectodermal groove of the first branchial cleft by the thin membrane which forms the floor of the groove. Pig. 267. — Semi-diagrammatic View of the Auditory Ossicles of an Embryo OF Six Weeks. i. Incus; J, jugular vein; m, malleus; mc, Meckel's cartilage; oc, capsule of otocyst; R, cartilage of the second branchial arch; st, stapes; VII, facial nerve.— (5te6eri- mann.) It has been seen in an earlier chapter that the axial mesoderm of each branchial arch gives rise to skeletal structures and muscles . The axial cartilage of the ventral portion of the first arch is what is known as Meckel's cartilage, but in that portion of the arch which forms the roof and anterior wall of the tympanic cavity, the cartilage becomes constricted to form two masses which later ossify to form the malleus and incus (Fig. 261, m and i), while the muscular tissue of this dorsal portion of the arch gives rise to the tensor tympani. Similarly, in the case of the second arch there is 446 THE EXTERNAL EAR to be found, dorsal to the extremity of the cartilage which forms the styloid process of the adult, a narrow plate of cartilage which forms an investment for the facial nerve (Fig. 267, VII), and dorsal to this a ring of cartilage (st) which surrounds a small stapedial artery and represents the stapes. ^^ Ithasbeenfound that in the rabbit the mass of cells from which the stapes m. 9^^ is formed is at its first appearance "'"—"""•. quite independent of the second ^ J branchial arch (Fuchs), and it has ' " ■ ' " been held to be a derivative of the ^ .^< , mesenchyme from which the periotic ^^ ^ "x capsule is formed. In later stages, '9J^ however, it becomes connected with * ; ; / the cartilage of the second branchial -.., 7* / arch, as shown in Fig. 267, and it is a ^ question whether this connection, p...^^ __^ which is transitory, does not really fi /' .--^^ ■•.. indicate the phylogenetic origin of ^.;' **"''■ \ «. the ossicle from the second arch ^. ^ I >^'; cartilage, its appearance as an inde- ; ... ,y ^ pendent structure being a secondary „ ,„ ^ ^ ontoerenetic phenomenon. However Fig. 268. — Diagrams Illus- o r- TRATiNG THE MoDE OF ExTEN- that may bc, thc stapedial artery dis- siON OF THE Tympanic Cavity • i 4. ^ a *-\^^ AROUND THE Auditory Ossicles, appears m later stages and the M, Malleus; m, spongy mesen- stapedius musclc, derived from the t^^^^^J^:^. musculature of the second branchial The broken line represents the ^rch and therefore suppHcd by the epithelial lining of the tympanic i i i cavity. facial nervc, becomes attached to the ossicle. The three ossicles at first lie embedded in the mesenchyme forming the roof of the primitive tympanic cavity, as does also the chorda tympani, a branch of the seventh nerve, as it passes into the substance of the first arch on the way to its destination. The mesenchyme in which these various structures are embedded is rather voluminous (Fig. 269), and after the end of the seventh month THE EXTERNAL EAR 447 becomes converted into a peculiar spongy tissue, which, toward the end of fetal life, gradually degenerates, the tympanic cavity at the same time expanding and wrapping itself around the ossicles and the muscles attached to them (Fig. 268) . The bones and their muscles, consequently, while appearing in the adult to traverse the tympanic cavity, are really completely enclosed within a layer of epithelium continuous with that lining the wall of the cavity, while the handle of the malleus and the chorda tympani lie between the epithelium of the outer wall of the cavity and the fibrous meso- derm which forms the tympanic membrane. The extension of the tympanic cavity does not, however, cease with its replacement of the degenerated spongy mesenchyme, but toward the end of fetal life it begins to invade the substance of the temporal bone by a process similar to that which produces the ethmoidal cells and the other osseous sinuses in connection with the nasal cavities (see p. 178). This process continues for some years after birth and results in the formation in the mastoid por- tion of the bone of the so-called mastoid cells , which communicate with the tympanic cavity and have an epithelial lining continuous with that of the cavity. The lower portion of the diverticulum from the first pharyngeal groove which gives rise to the tympanic cavity becomes con- verted into the Eustachian tube. During development the lumen of the tube disappears for a time, probably owing to a pro- liferation of its lining epithelium, but it is re-established before birth. In the account of the development of the ear-bones above it is held that the malleus and incus are derivatives of the first branchial (mandibular) arch and the stapes probably of the second. This view represents the general consensus of recent workers on the difl&cult ques- tion of the origin of these bones, but it should be mentioned that nearly all possible modes of origin have been at one time or other suggested. The malleus has very generally been accepted as coming from the first arch, and the same is true of the incus, although some earlier authors have assigned it to the second arch. ■ But with regard to the stapes the opinions have been very varied. It has been held to be derived from the first arch, from the second arch, from neither one nor the other, but from I the cartilaginous investment of the otocyst, or, finally, it has been held 448 THE EXTERNAL EAR to have a compound origin, its arch being a product of the second arch while its basal plate was a part of the otocyst investment. The Development of the Tympanic Membrane and of the Outer Ear. — Just as the tympanic cavity is formed from the endodermal groove of the first branchial cleft, so the outer ear owes its origin to the ectodermal groove of the same cleft and to the neighboring Fig. 269. — Horizontal Section Passing through the Dorsal Wall of the External Auditory Meatus in an Embryo of 4.5 mm. c. Cochlea; de, endolymphatic duct; i, incus; /5, transverse sinus; w, malleus; me, meatus auditorius externus; me', cavity of the meatus; s, sacculus; sc, lateral semi- circular canal; sc\ posterior semicircular canal; st, stapes; t, tympanic cavity; u, utriculus; 7, facial nerve. — (Siebenmann.) arches. The dorsal and most ventral portions of the groove flat- ten out and disappear, but the median portion deepens to form, at about the end of the second month, a funnel-shaped cavity which corresponds to the outer portion of the external auditory meatus. THE EXTERNAL EAR 449 From the inner end of this a solid ingrowth of ectoderm takes place, and this, enlarging at its inner end to form a disk-like mass, comes into relation with the gelatinous mesoderm which surrounds the malleus and chorda tympani. At about the seventh month a split occurs in the disk- like mass (Fig. 269), separating it into an outer and an inner layer, the latter of which becomes the outer epithelium of the tympanic membrane. Later, the split extends / ;' . C -rp^ Fig. 270. — Stages in the Development of the Auricle. A, Embryo of ii mm.; B, of 13.6 mm., C, of 15 mm.; D, at the beginning of the third month; R, fetus of 8.5 cm.; F, fetus at term, — (His.) Outward in the substance of the ectodermal ingrowth and eventually unites with the funnel-shaped cavity to complete the external meatus. The tympanic membrane is formed in considerable part from the substance of the first branchial arch, the area in which it occurs not being primarily part of the wall of the tympanic cavity, 29 450 THE EXTERNAL EAR but being brought into it secondarily by the expansion of the cavity. The membrane itself is mesodermal, in origin and is lined on its outer surface by an ectodermal and on the inner by an endodermal epithelium. The auricle {pinna) owes its origin to the portions of the first and second arches which bound the entrance of the external meatus. Upon the posterior edge of the first arch there appear about the end of the fourth week two transverse furrows which mark off three tubercles (Fig. 270, A^ 1-3) and on the anterior edge of the second arch a corresponding number of tubercles (4-6) is formed, while, in addition, a longitudinal furrow, running down the middle of the arch, marks off a ridge {c) lying posterior to the tubercles. From these six tubercles and the ridge are developed the various parts of the auricle, as may be seen from Fig. 270 which represents the transformation as described by His. According to this, the most ventral tubercle of the first arch (i) gives rise to the tragus J and the middle one (5) of the second arch furnishes the antitragus. The middle and dorsal tubercles of the first arch (2 and 3) unite with the ridge (c) to produce the helix, while from the dorsal tubercle of the second arch (4) is produced the antehelix and from the ventral one (6) the lobule. More recent observations however, seem to indicate that the lobule is an accessory structure unrelated to the tubercles and that the sixth tubercle gives rise to the antitragus, while the fifth is either included in the anthelix or else disappears. It is noteworthy that up to about the third month of development the upper and posterior portion of the helix is bent forward so as to conceal the anthelix (Fig. 270, D)\ it is just about a corresponding stage that the pointed form of the ear seen in the lower mammals makes its appearance, and it is evident that, were it not for the forward bending, the human ear would also be assuming at this stage a more or less pointed form. Indeed, there is usually to be found upon the incurved edge of the helix, some distance below the upper border of the auricle, a more or less distinct tubercle, known as Darwin's tubercle, which seems to represent the point of the typical mammalian ear, and is, ac- cordingly, the morphological apex of the pinna. THE EYE 451 There seems to be little room for doubt that the otocyst belongs primarily to the system of lateral line sense-organs, but a discussion of this interesting question would necessitate a consideration of details concerning the development of the lower vertebrates which would be foreign to the general plan of this book. It may be recalled, however, that the analysis of the components of the cranial nerves described on page 420 refers the auditory nerve to the lateral line system. 0. * ^^ Pig. 271. — Early Stages in the Development of the Lens in a Rabbit Embryo. The nucleated layer to the left is the ectoderm and the thicker lens epithelium, beneath which is the outer wall of the optic evagination; above and below between the two is mesenchyme. — (Rabl.) The Development of the Eye. — The first indications of the development of the eye are to be found in a pair of hollow out- 452 THE EYE growths from the side of the first primary brain vesicle, at a level which corresponds to the junction of the dorsal and ventral zones. Each evagination is directed at first upward and backward, and, enlarging at its extremity, it soon shows a differentiation into a terminal bulb and a stalk connecting the bulb with the brain (Fig. 237). At an early stage the bulb comes into apposition with the ectoderm of the side of the head, and this, over the area of con- tact, becomes thickened and then depressed to form the beginning of the future lens (Fig. 271). Fig. 272. — Reconstruction of the Brain of an Embryo of Pour Weeks show- ing THE Shorioid Fissure. — (His.) As the result of the depression of the lens ectoderm, the outer wall of the optic bulb becomes pushed inward toward the inner wall, and this invagination continuing until the two walls come into contact, the bulb is transformed into a double-walled cup, the optic cup, in the mouth of which lies the lens (Fig. 273). The cup is not perfect, however, since the invagination affects not only the optic bulb, but also extends medially on the posterior surface of the stalk, forming upon this a longitudinal groove and producing a defect of the ventral wall of the cup, known as the chorioidal fissure (Fig. 272). The groove and fissure become oc- cupied by mesodermal tissue, and in this, at about the fifth week, a blood-vessel develops which traverses the cavity of the cup to reach the lens and is known as the arteria hyaloidea. THE EYE 453 In the meantime further changes have been taking place in the lens. The ectodermal depression which represents it gradu- ally deepens to form a cup, the lips of which approximate and finally meet, so that the cup is converted into a vesicle which finally separates completely from the ectoderm (Fig. 273), much in the same way as the otocyst does. As the lens vesicle is con- FiG. 273. — Horizontal Section through the Bye of an Embryo Pig of 7 mm. Br, Diencephalon; Ec, ectoderm; I, lens; P, pigment, and R, retinal layers of the retina. stricted off, the surrounding mesodermal tissue grows in to form a layer between it and the overlying ectoderm, and a split appear- ing in the layer divides it into an outer thicker portion, which represents the cornea, and an inner thinner portion, which covers the outer surface of the lens and becomes highly vascular. The cavity between these two portions represents the anterior chamber of the eye. The cavity of the optic cup has also become filled 454 THE LENS by a peculiar tissue which represents the vitreous humors while the mesodermal tissue surrounding the cup condenses to form a strong investment for it, which is externally continuous with the cornea, and at about the sixth week shows a differentiation into an inner vascular layer, the chorioid coat, and an outer denser one, which becomes the sclerotic coat. The various processes resulting in the formation of the eye, which have thus been rapidly sketched, may now be considered in greater detail. The Development of the Lens. — When the lens vesicle is com- plete, it forms a more or less spherical sac lying beneath the super- ficial ectoderm and containing in its cavity a few cells, either scattered or in groups (Fig. 273). These cells, which have wandered into the cavity of the vesicle from its walls, take no part in the further development of the lens, but early undergo complete degeneration, and the first change which is concerned with the actual formation of the lens is an increase in the height of the cells forming its inner wall and a thinning out of its outer wall (Fig. 274, A). These changes continuing, the outer half ot the vesicle becomes converted into a single layer of somewhat flat cells which persist in the adult condition to form the anterior epithelium of the lens, while the cells of the posterior wall form a marked projection into the cavity of the vesicle and eventually completely obliterate it, coming into contact with the inner surface of the anterior epithelium (Fig. 274 5). These posterior elongated cells form, then, the principal mass of the lens, and constitute what are known as the lens fibers. At first those situated at the center of the posterior wall are the longest, the more peripheral ones gradually diminishing in length until at the equator of the lens they become continuous with and pass into the anterior epithelium. As the lens increase in size, however, the most centrally situated cells fail to elongate as rapidly as the more peripheral ones and are pushed in toward the center of the lens, the more peripheral fibers meeting below them along a line passing across the inner surface of the lens. The disparity of growth continuing, a similar sutural line appears THE LENS 455 v»M«f?«' •••s^/ Fig. 274. — Sections through the Lens (A) of Human Embryo of Thirty to Thirty-one Days and {B) of Pig Embryo of 36 mm. — (Rabl.) 456 THE LENS on the outer surface beneath the anterior epithelium, and the fibers become arranged in concentric layers around a central core composed of the shorter fibers. In the human eye the line of suture of the peripheral fibers becomes bent so as to consist of two limbs which meet at an angle, and from the angle a new Fig. 275. -Posterior (Inner) Surface of the Lens from an Adult showing thi SuTURAL Lines. — (Rabl.) sutural line develops during embryonic life, so that the sutur< assumes the form of a three-rayed star. In later life the star* become more complicated, being either six-rayed or more usuall} nine-rayed in the adult condition (Fig. 275). As early as the second month of development the lens vesicle becomes completely invested by the mesodermal tissue in whicl blood-vessels are developed in considerable numbers, whence th< THE OPTIC CUP 457 investment is termed the tunica vasculosa lentis (Fig. 283, tv). The arteries of the tunic are in connection principally with the hyaloid artery of the vitreous humor (Fig. 288), and consist of numerous" fine branches which envelop the lens and terminate in loops almost at the center of its outer surface. This tunic undergoes degenera- tion after the seventh month of development, by which time the lens has completed its period of most active growth, and, as a rule, completely disappears before birth. Occasionally, however, it may persist to a greater or less extent, the persistence of the por- tion covering the outer surface of the lens, known as the memhrana pupillarisj causing the malformation known as congenital atresia of the pupil. In addition to the vascular tunic, the lens is surrounded by a non-cellular membrane termed the capsule. The origin of this structure is still in doubt, some observers maintaining that it is a product of the investing mesoderm, while others hold it to be a product of the lens epithelium. It is interesting from the standpoint of developmental mechanics to note that W. H. Lewis and Spemann have shown that, in the Am- phibia, contact of the optic vesicle with the ectoderm is necessary for the formation of the lens, and, furthermore, if the vesicle be transplanted to other regions of the body of a larva, a lens will be developed from the ectoderm with which it is then in contact, even in the abdominal region. The Development of the Optic Cup. — When the invagination of the outer wall of the optic bulb is completed, the margins of the resulting cup are opposite the sides of the lens vesicle (Fig. 273), but with the enlargement of the lens and cup the margins of the latter gradually come to lie in front of — that is to say, upon the outer surface of — the lens, forming the boundary of the opening known as the pupil. The lens, consequently, is brought to lie within the mouth of the optic cup, and that portion of the latter which covers the lens takes part in the formation of the iris and the adjacent ciliary body, while its posterior portion gives rise to the retina. The chorioidal fissure normally disappears during the sixth or seventh week of development by a fusion of its lips, and not until 458 THE IRIS AND CILIARY BODY this is accomplished does the term cup truly describe the form assumed by the optic bulb after the invagination of its outer wall. In certain cases the lips of the fissure fail to unite perfectly, pro- ducing the defect of the eye known as colohoma; this may vary in its extent, sometimes affecting both the iris and the retina and forming what is termed coloboma iridis, and at others being confined to the retinal portion of the cup, in which case it is termed coloboma chorioidae. Up to a certain stage the differentiation of the two layers which form the optic cup proceeds along similar lines, in both the ciliary and retinal regions. The layer which . represents the original internal portion of the bulb does not thicken as the cup increases in size, and becomes also the seat of a deposition of dark pigment, whence it may be termed the pigment layer of the cup; while th< other layer — that formed by the invagination of the outer portioi of the bulb, and which may be termed the retinal layer — remain^ much thicker (Fig. 273) and in its proximal portions even increases in thickness. Later, however, the development of the ciliary and retinal portions of the retinal layers differs, and it will be con- venient to consider first the history of the ciliary portion. The Development of the Iris and Ciliary Body. — The first change noticeable in the ciliary portion of the retinal layer is its thinning out, a process which continues until the layer consists, like th< pigment layer, of but a single layer of cells (Fig. 276), the transi- tion of which to the thicker retinal portion of the layer is some- what abrupt and corresponds to what is termed the ora serrata ii adult anatomy. In embryos of 10.2 cm. the retinal layer through- out its entire extent is readily distinguishable from the pigment layer by the absence in it of all pigmentation, but in older forma this distinction gradually diminishes in the iris region, the retinal layer there acquiring pigment and forming the uvea. When the anterior chamber of the eye is formed by the splitting of the mesoderm which has grown in between the superficial ecto- derm and the outer surface of the lens, the peripheral portions o: its posterior (inner) wall are in relation with the ciliary portion of the optic cup and give rise to the stroma of the ciliary body anc THE IRIS AND CILIARY BODY 45Q of the iris (Fig. 276), this latter being continuous with the tunica vasculosa lentis so long as that structure persists (Fig. 283). In embryos of about 14.5 cm. the ciliary portion of the cup becomes thrown into radiating folds (Fig. 276), as if by a too rapid growth, and into the folds lamellae of mesoderm project from the stroma. These folds occur not only throughout the region of the ciHary body, but also extend into the iris region, where, however, they are but temporary structures, disappearing entirely by the end :"^^m. eit««MBi»«»« wf»#.«ri««k«aj(iM|^^^ ***i«ii-j Pm Fig. 276. — Radial Section through the Iris of an Embryo of 19 cm. AE, Pigment layer; CC, ciliary folds; IE, retinal layer; I.Str, iris stroma; Pm, pupil- lary membrane; Rs, marginal sinus; Sph, sphincter iridis. — (Szili.) of the fifth month. The folds in the region of the corpus ciliare persist and produce the ciliary processes of the adult eye. Embedded in the substance of the iris stroma in the adult are non-striped muscle-fibers, which constitute the sphincter and dila- tator iridis. It has long been supposed that these fibers were dif- ferentiated from the stroma of the iris, but recent observations have shown that they arise from the cells of the pigment layer of the optic cup, the sphincter appearing near the pupillary border (Fig. 276, Sph)y while the dilatator is more peripheral. 460 THE RETINA The Development of the Retina. — Throughout the retinal region of the cup the pigment layer, undergoing the same changes as in the ciliary region, forms the pigment layer of the retina (Fig. 274, p). The retinal layer increases in thickness and early becomes differentiated into two strata (Fig. 273), a thicker one lying next the pigment layer and containing numerous nuclei, and a thinner one containing no nuclei. The thinner layer, from its position and O 000 o^ Oo Fig. 277. — Portion of a Transverse Section of the Retina of a New-born Rabbit. ch. Chorioid coat; g, ganglion-cell layer; r, oiiter layer of nuclei; p, pigment layer. — (Falchi.) structure, suggests an homology with the marginal velum of the central nervous system, and probably becomes converted into the nerve-fiber layer of the adult retina, the axis-cylinder processes of the ganglion cells passing into it on their way to the optic nerve. The thicker layer similarly suggests a comparison with the mantle layer of the cord and brain, and in embryos of 38 mm. it be- comes differentiated into two secondary layers (Fig. 277), that nearest the pigment layer (/•) consisting of smaller and more deeply THE RETINA 461 staining nuclei, probably representing the rod and cone and bi- polar cells of the adult retina, while the inner layer, that nearest the marginal velum, has larger nuclei and is presumably composed of the ganglion cells. Little is as yet known concerning the further differentiation of the nervous elements of the human retina, but the history of some of them has been traced in the cat, in which, as in other mammals, Fig. 278. — Diagram showing the Development of the Retinal Elements. a. Cone cell in the unipolar, and b, in the bipolar stage; c, rod cells in the unipolar, and d, in the bipolar stage; e, bipolar cells; / and i, amacrine cells; g, horizontal cells; h, ganglion cells; k, M tiller's fiber; /, external limiting membrane. — (Kallius, after Cajal.) the histogenetic processes take place at a relatively later period than in man. Of the histogenesis of the inner layer the informa- tion is rather scant, but it may be stated that the ganglion cells are the earliest of all the elements of the retina to become recogniz- able. The rod and cone cells, when first distinguishable, are unipolar cells (Fig. 278, a and c), their single processes extending outward from the cell-bodies to the external limiting membrane which bounds the outer surface of the retinal layer. Even at an 462 THE OPTIC NERVE early stage the cone cells (a) are distinguishable from the rod cells (c) by their more decided reaction to silver salts, and at first both kinds of cells are scattered throughout the thickness of the layer from which they arise. Later, a fine process grows out from the inner end of each cell, which thus assumes a bipolar form (Fig. 278, b and d), and, later still, the cells gradually migrate toward the external limiting membrane, beneath which they form a definite layer in the adult. In the meantime there appears oppo- site the outer end of each cell a rounded eminence projecting from the outer surface of the external limiting membrance into the pig- ment layer. The eminences over the cone cells are larger than those over the rod cells, and later, as both increase in length, they become recognizable by their shape as the rods and cones. The bipolar cells are not easily distinguishable in the early stages of their differentiation from the other cells with which they are mingled, but it is believed that they are represented by cells which are bipolar when the rod and cone cells are still in a unipolar condition (Fig. 278, e). If this identification be correct, then it is noteworthy that at first their outer processes extend as far as the external limiting membrane and must later shorten or fail to elongate until their outer ends lie in what is termed the outer granular layer of the retina, where they stand in relation to the inner ends of the rod and cone cell processes. Of the development of the amacrine (/, i) and horizontal cells (g) of the retina little is known. From their position in new-born kittens it seems prob- able that the former are derived from cells of the same layer as the ganglion cells, while the horizontal cells may belong to the outer layer. In addition to the various nerve-elements mentioned above the retina also contains neuroglial elements known as Miiller's fibers (Fig. 278, k), which traverse the entire thickness of the retina. The development of these cells has not yet been thoroughly traced, but they resemble closely the ependymal cells observable in early stages of the spinal cord. The Development of the Optic Nerve. — The observations on the development of the retina have shown very clearly that the great THE OPTIC NERVE 463 majority of the fibers of the optic nerve are axis- cylinders of the ganglion cells of the retina and grow from these cells along the optic stalk toward the brain. Their embryonic history has been traced most thoroughly in rat embryos (Robinson), and what follows is based upon what has been observed in that animal. The optic stalk, being an outgrowth from the brain, is at first a hollow structure, its cavity communicating with that of the third ventricle at one end and with that of the optic bulb at the other. When the chorioid fissure is developed, it extends, as has already been described, for some distance along the posterior surface of the stalk and has lying in it a portion of the hyaloid artery. Later, when the lips of the fissure fuse, the artery becomes enclosed within the stalk to form the arteria centralis retincB of the adult (Fig. 281). By the formation of the fissure the original cavity of the distal portion of the stalk becomes obHterated, and at ^^^ ^79. -Diagrammatic the same time the ventral and posterior Longitudinal Section of the walls of the stalk are brought into con- tinuity with the retinal layer of the optic cup, and so opportunity is given for the passage of the axis-cylinders of the ganglion cells along those walls (Fig. 279). At an early stage a section of the proximal portion of the optic stalk (Fig. 280, A) shows the central cavity surrounded by a number of nuclei representing the mantle layer, and surrounding these a non-nucleated layer, re- sembling the marginal velum and continuous distally with the similar layer of the retina. When the gamglion cells of the latter begin to send out their axis-cylinder processes, these pass into the retinal marginal velum and converge in this layer tow;ard the bottom of the chorioidal fissure, so reaching the ventral wall of the optic stalk, in the velum of which they may be distinguished in rat embryos of 4 mm., and still more clearly in those of 9 mm. Optic Cup and Stalk passing THROUGH the ChORIOID FIS- SURE. Ah, Hyaloid artery; L, lens; On, fibers of the optic nerve; Os, optic stalk; PI, pigment layer, and R, retinal layer of the retina. 464 tHH- OPTIC NERVE (Fig. 280, A). Later, as the fibers become more numerous, they gradually invade the lateral and finally the dorsal walls of the stalk and, at the same time, the mantle cells of the stalk become more scattered and assume the form of connective-tissue (neurogUa) cells, while the original cavity of the stalk is gradually obHterated (Fig. 280, B). Finally, the stalk becomes a solid mass of nerve- fibers, among which the altered mantle cells are scattered. From what has been stated above it will be seen that the sensory cells of the eye belong to a somewhat different category from those of the other sense-organs. Embryologically they are a specialized portion of /' . '.. . A B Fig. 280. — Transverse Sections through the Proximal Part of the Optic Stalk of Rat Embryos of (A) 9 mm. and {B) ii mm. — (Robinson.) the mantle layer of the medullary canal, whereas in the other organs they are peripheral structures either representing or being associated with representatives of posterior root ganglion cells. Viewed from this standpoint, and taking into consideration the fact that the sensory por- tion of the retina is formed from the invaginated part of the optic bulb, some light is thrown upon the inverted arrangement of the retinal ele- ments, the rods and cones being directed away from the source of light. The normal relations of the mantle layer and marginal velum are re- tained in the retina, and the latter serving as a conducting layer for the axis-cylinders of the mantle layer (ganglion) cells, the layer of nerve- fibers becomes interposed between the source of light and the sensory cells. Furthermore, it may be pointed out that if the differentiation of the retina be imagined to take place before the closure of the medullary canal — a condition which is indicated in some of the lower vertebrates — there would be then no inversion of the elements, this peculiarity being due to the conversion of the medullary plate into a tube, and more espe- THE VITREOUS HUMOR 465 cially to the fact that the retina develops from the outer wall of the optic cup. In certain reptiles in which an eye is developed in connection with the epiphysial outgrowths of the diencephalon, the retinal portion of this pineal eye is formed from the inner layer of the bulb, and in this case there is no inversion of the elements. A justification of the exclusion of the optic nerve from the category which includes the other cranial nerves has now been presented. For if the retina be regarded as a portion of the central nervous system, it is clear that the nerve is not a nerve at all in the strict sense of that word, but is a tract, confined throughout its entire extent within the central nervous system and comparable to such groups of fibers as the direct cerebellar or fillet tracts of that system. The Development of the Vitreous Humor. — It has already been pointed out (p. 452) that a blood-vessel, the hyaloid artery, ac- companied by some mesodermal tissue makes its way into the r Fig. 281. — Reconstruction of a Portion of the Eye of an Embryo of 13.8 mm. ah. Hyaloid artery; ch, chorioid coat; /, lens; r, retina. — {His.) cavity of the optic cup through the chorioid fissure. On the closure of the fissure the artery becomes enclosed within the optic stalk and appears to penetrate the retina, upon the surface of which its branches ramify. In the embryo the artery does not, however, terminate in these branches as it does in the adult, but is continued on through the cavity of the optic cup (Fig. 281) to reach the lens, around which it sends branches to form the tunica vasculosa lentis. According to some authors, the formation of the vitreous humor is closely associated with the development of this artery, the humor being merely a transudate from it, while others have main- tained that it is a derivative of the mesoderm which accompanies 30 466 THE VITREOUS HUMOR the vessel, and is therefore to be regarded as a peculiar gelatinuous form of connective tissue. More recently, however, renewed observations by several authors have resulted in the deposition of the mesoderm from the chief role in the formation of the vitreous and the substitution in it of the retina. At an early stage of development delicate protoplasmic processes may be seen pro- jecting from the surface of the retinal layer into the cavity of the Fig. 282. — Transverse Section through the Ciliary Region of a Chick Embryo of Sixteen Days. ac. Anterior chamber of the eye; c/, conjunctiva; co, cornea; *', iris; Z, lens; mc, ciliary muscle; rl, retinal layer of optic cup; 5/, spaces of Pontana; si, suspensory ligament of the lens; v, vitreous humor. — {^Angelucci.^ optic cup, these processes probably arising from those cells which will later form the Miiller's (neuroglia) fibers of the retina. As development proceeds they increase in length, forming a dense and very fine fibrillar reticulum traversing the space between the lens and the retina and constituting the primary vitreous humor. The formation of the fibers is especially active in the ciliary portion of the retina and it is probable that it is from some of the fibers developing in this region that the suspensory ligament of the lens THE CORNEA 467 {zonula Zinnii) (Fig. 282, si) is formed, spaces which occur between the fibers of the ligament enlarging to produce a cavity traversed by scattered fibers and known as the canal of Petit. A participation of similar protoplasmic prolongations from the cells of the lens in the formation of the vitreous humor has been maintained (von Lenhossek) and as strenuously denied. But it is generally admitted that at the time when the hyaloid artery penetrates the vitreous to form the tunica vasculosa lentis it carries with it certain mesodermal elements, whose fate is at present un- certain. It has been held that they take part in the formation of the definite vitreous, which, according to this view, is of mixed origin, being partly ectodermal and partly mesodermal (Van Pee), and, on the contrary, it has been maintained that they eventually undergo complete degeneration, the vitreous being of purely ectodermal origin (von Kolliker). The degeneration of the mesodermal elements which the latter view supposes is associated with the degeneration of the hyaloid artery. This begins in human embryos in the third month and is completed during the ninth month, the only trace after birth of the existence of the vessel being a more fluid consistency of the axis of the vitreous humor, this more fluid portion representing the space originally occupied by the artery and forming what is termed the hyaloid canal {canal of Cloquet). The Development of the Outer Coat of the Eye, of the Cornea, and of the Anterior Chamber. — Soon after the formation of the optic bulb a condensation of the mesoderm cells around it occurs, form- ing a capsule. Over the medial portions of the optic cup the further differentiation of this capsule is comparatively simple, resulting in the formation of two layers, an inner vascular and an outer denser and fibrous, the former becoming the chorioid coat of the adult eye and the latter the sclera. More laterally, however, the processes are more complicated. After the lens has separated from the surface ectoderm a thin layer of mesoderm grows in between the two structures and later gives place to a layer of homogeneous substance in which a few cells, more numerous laterally than at the center, are embedded. 468 THE ANTERIOR CHAMBER OF THE EYE Still later cells from the adjacent mesenchyme grow into the layer, which increases considerably in thickness, and blood-vessels also grow into that portion of it which is in contact with the outer surface of the lens. At this stage the interval between the surface ectoderm and the lens is occupied by a solid mass of mesodermal tissue (Fig. 283, co and tv), but as development proceeds, small spaces {ac) filled with fluid begin to appear toward the inner por- tion of the mass, and these, increasing in number and size, eventu- ac eC' Fig. 283. — Transverse Section through the Ciliary Region of a Pig Embryo OF 23 MM. ac. Anterior chamber of the eye; co, cornea; ec, ectoderm; /, lens; mc, ciliary mus- cle; p, pigment layer of the optic cup; r, retinal layer; tv, tunica vasculosa lentis. — {Angelucci.) ally fuse together to form a single cavity which divides the mass into an inner and an outer portion. The cavity is the anterior chamber of the eye, and it has served to separate the cornea (co) from the tunica vasculosa lentis (/y), and, extending laterally in all directions, it also separates from the cornea the mesenchyme which rests upon the marginal portion of the optic cup and constitutes I the stroma of the iris. Cells arrange themselves on the corneal surface of the cavity to form a continuous endothelial layer, and . THE EYELIDS 469 the mesenchyme which forms the peripheral boundary of the cavity assumes a fibrous character and forms the ligamentum pedinatum iridis, among the fibers of which cavities, known as' the spaces of Fontana (Fig. 282, 5/), apppear. Beyond the margins of the cavity the corneal tissue is directly continuous with the sclerotic, beneath the margin of which is a distinctly thickened portion of mesenchyme resting upon the ciliary processes and forming the stroma of the ciliary body, as well as giving rise to the muscle tissue which constitutes the ciliary muscle (Figs. 282 and 283, mc). The ectoderm which covers the outer surface of the eye does not proceed beyond the stage when it consists of several layers of cells, and never develops a stratum corneum. In the corneal region it rests directly upon the corneal tissue, which is thickened slightly upon its outer surface to form the anterior elastic lamina; more peripherally, however, a quantity of loose mesodermal tissue lies between the ectoderm and the outer surface of the sclerotic, and, together with the ectoderm, forms the conjunctiva (Fig. 282, cj). The Development of the Accessory Apparatus of the Eye. — The eyelids make their appearance at an early stage as two folds of skin, one a short distance above and the other below the cornea. The center of the folds is at first occupied by indifferent mesodermal tissue, which later becomes modified to form the connective tissue of the lids and the tarsal cartilage, the muscle tissue probably secondarily growing into the lids as a result of the spreading of the platysma over the face, the orbicularis oculi apparently being a derivative of that sheet of muscle tissue. At about the beginning of the third month the lids have be- come sufficiently large to meet one another, whereupon the thick- ened epithelium which has formed upon their edges unites and the lids fuse together, in which condition they remain until shortly before birth. During the stage of fusion the eyelashes (Fig. 284, h) develop at the edges of the lids, having the same developmental history as ordinary hairs, and from the fused epithelium of each lid there grow upward or downward, as the case may be, into the mesodermic tissue, solid rods of ectoderm, certain of which early 470 THE EYELIDS give off numerous short lateral processes and become recognizable as the tarsal (Meibomian) glands (m), while others retain the simple cylindrical form and represent the glands of Moll. When the eyelids separate, these solid ingrowths become hollow by a breaking down of their central cells, just as in the sebaceous and sudoriparous glands of the skin, the tarsal glands being really Fig. 284. — Section through the Margins of the Fused Eyelids in an Embryo OF Six Months. h. Eyelash; U, lower lid; m, tarsal gland; mu, muscle bundle; ul, upper lid. — {Schiveig- ger Seidl.) modifications of the former glands, while the glands of Moll are probably to be regarded as specialized sudoriparous glands. A third fold of skin, in addition to the two which produce the eyelids, is also developed in connection with the eye, form- ing the plica semilunaris. This is a rudimentary third eyelid, representing the nictitating membrane which is fairly well developed in many of the lower mammals and especially well in birds. THE LACHRYMAL GLAND 471 The lachrymal gland is developed at about the third month as a number of branching outgrowths of the ectoderm into the adjacent mesoderm along the outer part of the line where the epithelium of the conjunctiva becomes continuous with that covering the inner surface of the upper eyelid. As in the other epidermal glands, the outgrowths and their branches are at first solid, later becoming hollow by the degeneration of their axial cells. The naso-lachrymal duct is developed in connection with the groove which, at an early stage in the development (Fig. 63), extends from the inner corner of the eye to the olfactory pit and is Fig. 285. — Diagram showing the Insertions of the Lachrymal Ducts in Embryos of 40 mm. and 170 mm., the Caruncula Lacrimalis being formed in the Latter. The eyelids are really fused at these stages but have been represented as separate for the sake of clearness. — {Ask.) bounded posteriorly by the maxillary process of the first visceral arch. The epithelium lying in the floor of this groove thickens toward the beginning of the sixth week to form a solid cord, which sinks into the subjacent mesoderm. From its upper end two outgrowths arise which become connected with the ectoderm of the edges of the upper and lower lids, respectively, and represent the lachrymal ducts ^ and, finally, the solid cord and its outgrowths acquire a lumen and a connection with the mucous membrane of the inferior meatus of the nasal cavity. The inferior duct connects with the border of the eyelid some distance lateral to the inner angle of the eye, and between its open- ing and the angle a number of tarsal glands develop. The superior j duct, on the other hand, opens at first close to the inner angle and 472 LITERATURE later moves laterally until its opening is opposite that of the infe- rior duct. During this change the portion of the lower lid between the opening of the inferior duct and the angle is drawn somewhat upward, and, with its glands, forms a small reddish nodule, resting upon the plica semilunaris and known as the caruncula lacrimalis (Fig. 285). LITERATURE G. Alexander: "Ueber Entwicklung und Bau des Pars inferior Labyrinthi der hoheren Saugethiere," Denkschr. kais. wissench. Acad. Wien, Math.-Naturw. Classe, Lxx, 1901. A. Angelucci: "Ueber Entwickelung und Bau des vorderen Uvealtractus der Verte- braten," Archir fur mikrosk. Anat., xrx, 1881. F. Ask: "Ueber Entwickelung der Caruneula lacrimalis beim Menschen, nebst Bemerkungen iiber die Entwickelung der Tranenrohrchen und derMeibom'schen Driisen," Anatom. Anzeiger, xxx, 1907. F. Ask: "Ueber die Entwicklung der Lidrander, der Tranenkarunkel und der Nick- haut beim Menschen, nebst Bemerkungen zur Entwicklung der Tranenabfiihr- ungswege," Anat. Hefte, xxxvi, 1908. B. Baginsky: "Zur Entwickelung der Gehorschnecke," Archiv fiir mikrosk. Anat., xxvni, 1886. W. M. Baldwin: "Die Entwicklung der Fasern der zonula Zinnii im Auge der weissen Maus nach der Geburt," Arch, fur mikrosk. Anat., lxxx, 191 2. E. A. Baumgartner: "The Development of the serous glands (von Ebner's) of the vallate papillae in man," Amer. Journ. Anat., xxn, 1917. I. Broman: "Die Entwickelungsgeschichte der Gehorknochelchen beim Menschen," Anat. Hefte, xi, 1898. S. Ramon y Cajal: "Nouvelles contributions a I'^tude histologique de la r6tine," Journ. deVAnat. et de la Physiol., xxxii, 1896. G. Cirincione: "Ueber den gegenwartigen Stand der Frage hinsichtlich der Genese des Glaskorpers," Arch, fiir Augenheilk., l, 1904. A. CoNHNo: "Ueber Bau and Entwicklung des Lidrandes beim Menschen," Arch, fiir Ophthalmol., lxvi, 1908. A. CoNTiNo: "Ueber die Entwicklung der Karunkel und der plica semilunaris beim Menschen," Arch, fiir Ophthalmol, lxxi, 1909. J. Disse: "Die erste Entwickelung der Riechnerven," Anat. Hefte, rx, 1897. B. Fleischer: "Die Entwickelung der Tranenrolirchen bei den Saugetiere/* Archiv fiir Ophthalmol., Lxn, 1906. H. FucHs: "Bemerkungen iiber die Herkunft und Entwickelung der Gehorknochel- chen bei Kanichen-Embryonen (nebst Bemerkungen iiber die Entwickelung des Knorpelskeletes der beiden ersten Visceralbogen)," Archiv. fiir Anat und Phys., Anat. Abth., Supplement, 1905. J. Graberg: "Beitrage zur Genese des Geschmacksorgans der Menschen," Morphol. Arbeiten, vii, 1898. J. A. Hammar: "Zur allgemeinen Morphologic der Schlundspalten des Menschen. LITERATURE 473 Zur Entwickelungsgeschichte des Mittelohrraumes, des ausseren Gehorganges und des Paukenfelles beim Menschen," Anat. Anzeiger, xx, 1901. J. A. Hammar: "Studien iiber Entwicklung des Vorderdarms und einiger angrenz~ ender Organe," Arch, fur mikrosk. Anat., lix, 1902. C. Heerfordt: "Studien iiber den Muse, dilatator pupillse sammt Angabe von gemeinschaftlicher Kennzeichen einiger Falle epithelialer Musculatur," Anat, Hefte, XIV. J. Hegetschweiler : "Die embryologische Entwickelung des Steigbugels," Archiv fiir Anat. und Physiol., Anat. Abth., 1898. F. Hochstetter: "Ueber die Bildung der primitiven Clioanen beim Menschen," Verhandl. Anat. Gesellsch., vi, 1892. W. His, Jr: "Die Entwickelungsgeschichte des Acustico-Facialisgebietes beim Menschen," Archiv fur Anat. und Physiol., Anat. Abth., Supplement, 1897. A. VON Kolliker: "Die Entwicklung und Bedeutung des Glaskorpers," Zeitschr. fiir wissensch. Zoolog., lxxvi, 1904. P. Lang: Zur Entwicklung des Tranenausfiihrsappa rates beim Menschen," Anat. Anzeiger,^' xxxviu, 191 1. G. Leboucq: "Contribution a I'^tude de I'histog^nSse de la retine che^ les mam- miferes," Arch. Anat., Microsc, x, 1909. J. Ma WAS and A. Magitot: "Etude sur le developpement du corps vitre et de la zonule chez I'homme," Arch. d'Anat. Microsc, xrv, 1912. V. VON Mihalkovicz: "Nasenhohle und Jacobsonsches Organ. Eine morpholog- ische Studie." AncU. Hefte, xi, 1898. J. L. Paulet: "Contribution a r6tude de I'organe de Jacobson chez I'embryon humain," Bibliogr. Anat., xvii, 1907. P. VAN Pee: "Recherches sur I'origine du corps vilre," Archiv de Biol., XK, 1902. C. W. Prentiss: "On the Development of the membrana tectoria with reference to its structure and attachments," Amer. Journ. Anal., xiv, 1913. C. Rabl: "Ueber den Bau und Entwickelung der Linse," Zeitschrift fur wissensch. Zoologie, Lxn and lxv, 1889; lxviii, 1899. A. Robinson: "On the Formation and Structure of the Optic Nerve and Its Relation to the Optic Stalk," Journal of Anat. and Physiol., xxx, 1896. G. Speciale-Cirincione: "Ueber die Entwicklung der Tranendruse beim Men- schen," Arch, fur Ophthalmol., lxix, 1908. J. P. Schaeffer: "The Genesis and Development of the Nasolachrymal Passages in Man," Amer. Journ. Anat., xiii, 191 2. U. Seefelder: "Beitrage zur Entwicklung des menschlichen Auges," Anat. Hefte, XLViii, 1 913. G. L. Streeter "On the Development of the Membranous Labyrinth and the Acoustic and Facial Nerves in the Human Embryo," Amer. Journ. of Anat., VI, 1907. G. L. Streeter: "The histogenesis and growth of the otic capsule and its contained periotic tissue-spaces in the human embryo," Publications Carnegie Inst., No. 227, Contrib. to Embryol. xx, 1919. N. VAN dER Stricht: "L'histogenese des parties constituantes du neuro6pith61ium acoustique, des taches et des cretes acoustiques et de I'organe de Corti," Arch. de Biol., xxin, 1908. 474 LITERATURE A. SziLi: "Zur Anatomic und Entwickelungsgeschichte der hinteren Irisschichten, mit besonderer Berucksichtigung des Musculus sphincter iridis des Menschen," Anat. Anzeiger,'KX, 1901. A. SziLi : " Ueber das Entstehen eines fibrillares Stiitzgewebes im Embryo und dessen Verbal tnis zur Glaskorperfrage," Anat. Hefte, xxxv, 1908. F. Tuckerman: "On the Development of the Taste Organs in Man," Journal of Anat. andFhysioL,-xxiv, 1889. R. Versari: "Ueber die Entwicklung der Blutgefasse des menschlichen Auges," Anat. Anzeigefy xxxv, 1909. CHAPTER XVII POST-NATAL DEVELOPMENT In the preceding pages attention has been directed principally to the changes which take place in the various organs during the period before birth, for, with a few exceptions, notably that of the liver, the general form and histological peculiarities of the various organs are acquired before that epoch. Development does not, however, cease with birth, and a few statements regard- ing the changes which take place in the interval between birth and maturity will not be out of place in a work of this kind. The conditions which obtain during embryonic life are so different from those to which the body must later adapt itself, that arrangements, such as those connected with the placental circula- tion, which are of fundamental importance during the life in utero, become of little or no use, while the relative importance of others is greatly diminished, and these changes react more or less profoundly on all parts of the body. Hence, although the post-natal development consists chiefly in the growth of the struc- tures formed during earlier stages, yet the growth is not equally rapid in all parts, and indeed in some organs there may even be a relative decrease in size. That this is true can be seen from the annexed figure (Fig. 286), which represents the body of a child and that of an adult man drawn as of the same height. The greater relative size of the head and upper part of the body in the child is very marked, and the central point of the height of the child is situated at about the level of the umbilicus, while in the man it is at the symphysis pubis. That there is a distinct change in the geometric form of the body during growth is also well shown by the following considera- tion (Thoma). Taking the average height of a new-born male as 500 mm., and that of a man of thirty years of age as 1686 mm., the 475 476 POST-NATAL DEVELOPMENT height of the body will have increased from birth to adolescence 1686 ~- — = 3-37 times. The child will weigh 3.1 kilos and the man 66.1 kilos, and if the specific gravity of the body with the included gases be taken in the one case as 0.90 and in the other as 0.93 then the volume of the child's body will be 3.44 liters and that of 71.08 the man's 71.08 liters, and the increase in volume will be 3-44 Fig. 286. — Child and Man Drawn as of the Same Height. — (Langer, from the "Growth of the Brain," Contemporary Science Series by permission of Charles Scribner's Sons.) 20.66. If the increase in volume had taken place without any alteration in the geometric form of the body, it should be equal to the cube of the increase in height; this, however, is 3.37^ = 38.27, a number well-nigh twice as large as the actual increase. But in addition to these changes, which are largely dependent upon differences in the supply of nutrition, there are others associ- ated with alterations in the general metabolism of the body. Up to adult life the constructive metabolism or anabolism is in excess POST-NATAL DEVELOPMENT 477 of the destructive metabolism or katabolism, but the amount of the excess is much greater during the earlier periods of develop-- ment and gradually diminishes as the adult condition is ap- proached. That this is true during intrauterine life is shown by the following figures, compiled by Donaldson: Age in Weeks Weight in Grams Age in Weeks Weight in Grams o (ovum) 0.0006 24 63s 4 — 28 1,220 8 4.0 32 1,700 12 20.0 36 2,240 i6 120.0 40 (birth) 3,250 20 . 285.0 From this table it may be seen that the embryo of eight weeks is six thousand six hundred and sixty-seven times as heavy as the ovum from which it started, and if the increase of growth for each of the succeeding periods of four weeks be represented as percent- ages, it will be seen that the rate of increase undergoes a rapid diminution after the sixteenth week, and from that on diminishes gradually but less rapidly, the figures being as follows : Periods of Weeks Percentage Increase Periods of Weeks Percentage Increase 8-12 12-16 16-20 20-24 400 500 ' 137 123 24-28 28-32 32-36 36-40 92 39 32 45 That the same is true in a general way of the growth after birth may be seen from the following table, representing the average weight of the body in English males at different years from birth up to twenty- three (Roberts), and also the percentage rate of mcrease. Certain interesting peculiarities in post-natal growth become apparent from an examination of this table. For while there is a general diminution in the rate of growth, yet there are marked 478 POST-NATAL DEVELOPMENT Year Number of Cases Weight in Kilograms Percentage Increase O 451 3.2 I — (10.8) (238) 2 2 14.7* (36)* 3 41 154 4.8* 4 I02 16.9 9-7 5 193 18. 1 71 6 224 20.1 II. 7 246 22.6 12.4 8 820 24.9 10.2 9 1,425 27.4 10. lO 1,464 30.6 II. 5 II 1,599 32.6 6.5 12 1,786 34.9 7.0 13 2,443 37.6 7-7 ■ 14 2,952 41.7 10.9 IS 3,118 46.6 II. 7 i6 2,235 53.9 157 17 2,496 59.3 lO.O i8 2,150 62.2 4-9 19 1,438 63.4 1.9 20 851 64.9 2.5 21 738 65.7 1.2 22 542 67.0 1.9 23 551 67.0 0.0 irregularities, the most noticeable being (i) a rather marked dimi- nution during the eleventh and twelfth years, followed by (2) a rapid acceleration which reaches its maximum at about the six- teenth year and then very rapidly diminishes. These irregulari- ties may be more clearly seen from the charts on p. 479, which represent the curves obtained by plotting the annual increase of weight in boys (Chart I) and girls (Chart II). The diminution and acceleration of growth referred to above are clearly observable and * From a comparison with other similar tables there is little doubt but that the weight given above for the second year is too high to be accepted as a good average. Consequently the percentage increase for the second year is too high and that for the third year too low. It may be mentioned that the weights in the original table are expressed in pounds avoirdupois and have been here converted into kilograms, and further the figures representing the percentag increase have been added. POST-NATAL DEVELOPMENT 479 it is interesting to note that they occur at earlier periods in girls than in boys, the diminution occurring in girls at the eighth and ninth years and the acceleration reaching its maximum at the thirteenth year. Considering, now, merely the general diminution in the rate of growth which occurs from birth to adult life, it becomes interesting I Am "x ii -^ i . ^' . 9 \> i^ 12 x3 u a X 17 m -t ' " T LbsM l/X -y^ « « V l^^X -' - #^^A ' JZ V t ^\\ I ^L Vr -. «- 4 ^^ It 3 -,3 - jfc ' i 2Z ns ' ^v ^2Z^ ^S^ ,. c ^^S yil^z '^r'c. • ..-^.^d^^^c 2=^^ ^22 „. X ^-^^"'^ ^S'^' ^ • 1 II / 2 a * 5 6 7 5 9 lO 11 iZ 13 H ti jf /7 ^r J "t: \ L^ ** y i Jj. # \^ i( " > :> V ^■x '// 5i :1 £^ 1/ 3L ^ -/ M T jt • ^ i ;!?' \/ s -~ ^ "Sfc/Jl ^± - -t Age Lbs/4 " 12 " JO ■• / '• 6 " f ' Z Fig. 287. — Curves Showing the Annual Increase in Weight in (I) Boys and (II) Girls. The faint line represents the curve from British statistics, the dotted line that from American (Bowditch), and the heavy line the average of the two. Before the f ixth year the data are unreliable. — {Stephenson.) to note to what extent the organs which are more immediately associated with the metabolic activities of the body undergo a rela- tive reduction in weight. The most important of these organs is undoubtedly the liver, but with it there must also be considered the thyreoid and thymus glands, and probably the suprarenal bodies. 48o POST-NATAL DEVELOPMENT In all these organs there is a marked diminution in size as com- pared with the weight of the body, as will be seen from the follow- ing table (H. Vierordt), which also includes data regarding other organs in which a marked relative diminution, not in all cases readily explainable, occurs. ABSOLUTE WEIGHT New-born and a IN GRAMS \dult Liver Thy- reoid Thy- mus Suprarenal Bodies Spleen Heart Kidney B-in 'goTd' 141. 7 1,819.0 4.85 33.8 8.15 26.9 7.05 7-4 10.6 163.0 23.6 300.6 233 305.9 381.0 1,430.9 1 5-5 3915 PERCENTAGE WEIGHT OF ENTIRE BODY New-born and Adult Heart Kidney Brain Liver Thy- reoid l^s 'XSS°' Spleen Spinal Cord 4.57 0.16 2.57 0.05 0.26 0.04 0.23 O.OI 0.34 0.76 0.25 0.46 0.75 0.46 12.29 2.16 0.18 0.06 Recent observations by Hammar render necessary some modifica- tion of the figures given for the thymus in the above table. He finds the average weight of the gland at birth to be 13.26 grams, and that the weight increases up to puberty, averaging 37.52 grams between the ages of II and 15. After that period it gradually diminishes, falling to 16.27 grams between 36 and 45, and to 6.0 grams between 66 and 75. Expressed in percentage of the body weight this gives a value in the new-born of 0.42 and in an individual of 50 years of 0.02, a difference much more striking than that shown in Vierordt's table. It must be mentioned, however, that the gland is subject to much individual variation, being largely influenced by nutritive conditions. The remaining organs, not included in the tables given above, when compared with the weight of the body, either show an in- crease or remain practically the same. POST-NATAL DEVELOPMENT 481 ABSOLUTE WEIGHT IN GRAMS New-born and Adult Skin and Sub- cutaneous Tissues Skeleton Musculature Stomach and Intestines Pancreas Lungs 611.75 11,765.0 425.5 11,575.0 776.5 28,732.0 65 1,364 3-5 97.6 54-1 994.9 PERCENTAGE OF BODY WEIGHT New-born and Adult Skin and Sub- cutaneous Tissues Skeleton Musculature Stomach and Intestines Pancreas Lungs 19-73 17.77 13.7 17.48 25.05 43.40 2.1 2.06 0. II 0.15 1.75 1.50 From this table it will be seen that the greatest increment of weight is that furnished by the muscles, the percentage weight of which is one and three-fourths times as great in the adult as in the child. The difference does not, however, depend upon the differ- entiation of additional muscles; there are just as many muscles in the new-born child as in the adult, and the increase is due merely to an enlargement of organs already present. The percentage weight of the digestive tract, pancreas, and lungs remains practically the same, while in the case of the skeleton there is an appreciable in- crease, and in that of the skin and subcutaneous tissue a slight diminution. The latter is readily understood when it is remem- bered that the area of the skin, granting that the geometric form of the body remains the same, would increase as the square of the length, while the mass of the body would increase as the cube, and hence in comparing weights the skin might be expected to show a diminution even greater than that shown in the table. The increase in the weight of the skeleton is due to a certain extent to growth, but chiefly to a completion of the ossification of the cartilage largely present at birth. A comparison of the weights of this system of organs does not, therefore, give evidence of the many changes of form which may be perceived in it during 31 482 POST-NATAL DEVELOPMENT the period under consideration, and attention may be drawn to some of the more important of these changes. In the spinal column one of the most noticeable pecularities observable in the new-born child is the absence of the curves so characteristic of the adult. These curves are due partly to the weight of the body, transmitted through the spinal column to the hip-joint in the erect position, and partly to the action of the mus- FiG. 288. -Longitudinal Section through the Sacrum of a New-born Female Child. — (Fehling.) cles, and it is not until the erect position is habitually assumed and the musculature gains in development that the curvatures become pronounced. Even the curve of the sacrum, so marked in the adult, is but slight in the new-born child, as may be seen from Fig. 285, in which the ventral surfaces of the first and second sacral vertebrae look more ventrally than posteriorly, so that there is no distinct promontory. POST-NATAL DEVELOPMENT 483 But, in addition to the appearance of the curvatures, other changes also occur after birth, the entire column becoming much_ more slender and the proportions of the lumbar and sacral vertebrae becoming quite different, as may be seen from the following table (Aeby): LENGTHS OF THE VERTEBRAL REGIONS EXPRESSED AS PERCENT- AGES OF THE ENTIRE COLUMN Age Cervical Thoracic Lumbar New-born child 25.6 23.3 20.3 19.7 22. I 47-5 46.7 45.6 47.2 46.6 26.8 Male 2 years 300 34.2 33.1 31.6 Male 5 years Male 1 1 years Male adult The cervical region diminishes in length, while the lumbar gains, the thoracic remaining approximately the same. It may be noticed, furthermore, that the difference between the two variable regions is greater during youth than in the adult, a condition possi- bly associated with the general more rapid development of the lower portion of the body made necessary by its imperfect develop- ment during fetal life. The difference is due to changes in the vertebrae, the intervertebral disks retaining approximately the same relative thickness throughout the period under consideration. The form of the thorax also alters, for whereas in the adult it is barrel-shaped, narrower at both top and bottom than in the middle, in the new-born child it is rather conical, the base of the cone being below. The difference depends upon slight differences in the form and articulations of the ribs, these being more horizon- tal in the child and the opening of the thorax directed more directly upward than in the adult. As regards the skull, the processes of growth are very compli- cated. Cranium and brain react on one another, and hence, in harmony with the relatively enormous size of the brain at birth, the cranial cavity has a relatively greater volume in the child than in the adult. The fact that the entire roof and a considerable part of the sides of the skull are formed of membrance bones which, at 484 POST-NATAL DEVELOPMENT birth, are not in sutural contact with one another throughout, gives opportunity for considerable modifications, and, furthermore, the base of the skull at the early stage still contains a considerable amount of unossified cartilage. Without entering into minute de- tails, it may be stated that the principal general changes which the skull undergoes in its post-natal development are (i) a relative elongation of its anterior portion and (2) an increase in the relative height of the maxillae . If a line be drawn between the central points of the occipital condyles, it will divide the base ot the skull into two portions, Fig. 289. — Skull of a New-born Child and of an Adult Man, Drawn as of Approximately the Same Size. — {Henke.) which in the child's skull are equal in length. The portion of the skull in front of a similar line in the adult skull is very much greater than that which lies behind, the proportion between the two parts being 5:3, against 3 : 3 in the child (Froriep) . There has, therefore, been a decidedly more rapid growth of the anterior portion of the skull, a growth which is associated with a cor- responding increase in the dorso-ventral dimensions of the maxillae. These bones, indeed, play a very important part in determining proportions of the skull at different periods. They are so the intimately associated with the cranial portions of the skull that their increase necessitates a corresponding increase in the anterior part of the cranium, and their increase in this direction standsjin relation to the development of the teeth, the eight teeth which are developed in each maxilla (including the premaxilla) in the adult re- POST-NATAL DEVELOPMENT 485 quiring a longer bone than do the five teeth of the primary dentition, these again requiring a greater length when completely developed than they do in their immature condition in the new-born child. But far more striking than the difference just described is that in the relative height of the cranial and facial regions (Fig. 289). It has been estimated that the volumes of the two portions have a ratio of 8 : 1 in the new-born child, 4 : i at five years of age, and 2:1 in the adult skull (Froriep), and these differences are due principally to changes in the vertical dimensions of the maxillae. As with the increase in length, the increase now under consideration is, to a certain extent at least, associated with the development of the teeth, these structures calling into existence the alveolar proc- esses which are practically wanting in the child at birth. But a more important factor is the development of the maxillary sin- uses, the practically solid bodies of the maxillae becoming trans- formed into hollow shells. These cavities, together with the sinuses of the sphenoid and frontal bones, which are also post-natal developments, seem to stand in relation to the increase in length of the anterior portion of the skull, serving to diminish the weight of the portion of the skull in front of the occipital condyles and so relieving the muscles of the neck of a considerable strain to which they would otherwise be subjected. These changes in the proportions of the skull have, of course, much to do with the changes in the general proportions of the face. But the changes which take place in the mandible are also impor- tant in this connection, and are similar to those of the maxillae in being associated with the development of the teeth. In the new- born child the horizontal ramus is proportionately shorter than in the adult, while the vertical ramus is very short and joins the horizontal one at an obtuse angle. The development of the teeth of the primary dentition, and later of the three molars, necessi- tates an elongation of the horizontal ramus equivalent to that occurring in the maxillae, and, at the same time, the separation of the alveolar borders of the two bones requires an elongation of the vertical ramus if the condyle is to preserve its contact with the mandibular fossa, and this, again, demands a diminu- 486 POST-NATAL DEVELOPMENT tion of the angle at which the rami join if the teeth of the two jaws are to be in proper apposition. In the bones of the appendicular skeleton secondary epiphy- sial centers play an important part in the ossification, and in few are these centers developed prior to birth, while the union of the epiphyses to the main portions of the bones take place only to- ward maturity. The dates at which the various primary and sec- ondary centers appear, and the time at which they unite, may be seen from the following table: UPPER EXTREMITY Rone Appearance of Appearance of Secondary Fusions of jDone Primary Center Centers Centers Clavide 6lh week. (At sternal end) 17th year. 20th year. Scapula. Body Sth week. ■! 2 acromial isth year. 2 on vertical border i6th year. > 20th year. Coracoid ist year. I Sth year. Head ist year. Great tuberosity 3d year. Lesser tuberosity sth year. 20th year. Humerus yth week. Inner condyle sth year. I Sth year. Capitellum 3d year. Trochlea loth year. 1 7th year. Outer condyle 14th year. Ulna yth week. Olecranon loth year i6th year. Distal epiphysis 4th year. iSth year. Radius yih week. Proximal epiphysis 5 th year. 17th year. Distal epiphysis 2d year 20th year. Capitatum. . . . I St year. Hamatum 2d year. Triquetrum . . . 3d year. Lunatum 4th year. Multangulum Sth year. majus. Navicular 6th year. Multangulum Sth year. minus. Pisiform 12 th year. Metacarpals . . 3d year. 20th year. Phalanges gth-iith week. 3d-sth years. 1 7th- 1 Sth years. The dates in italics are before birth. POST-NATAL DEVELOPMENT 487 LOWER EXTREMITY Bene Appearance of Appearance of Seconadry Fusion of Pnmary Centei Centers Centers ~ Ilium gth week. 4th month. Crest I sth year. Ischium Anterior inferior spine 15 th year. Tuberosity 15 th year. 2 2d year. Pubis 4th month. Crest i8th vear. Patella Cartilage appears at 4th month, ossification in 3d year. Head ist year. 20th year. Femur yth week. Great trochanter 4th year. 19th year. Lesser trochanter I3th-i4th year I Sth year. Condyle gth month 2 1 st year. Tibia jth week. Head end of gth month. Distal end 2d year. 2ist-2Sth year. I Sth year. Fibula Sth week. Upper epiphysis 5 th year. 2 ist year. Lower epiphysis 2d year. 20th year. Talus 7th month. Calcaneus 6th month. loth year. 1 6th year. Cuboid A few days after birth. Navicular 4th year. Cuneiforms . . . I St year. Metatarsals . . . gth week. 3d year. 20th year. Phalanges gth-i2th week. 4th-8th year« 1 7th- 1 Sth years The dates in italics are before biith. So far as the actual changes in the form of the appendicular bones are concerned, these are most marked in the case of the lower limb. The ossa innominata alter somewhat in their proportions after birth, a fact which may conveniently be demonstrated by con- sidering the changes which occur in the proportions of the pelvic diameters, although it must be remembered that these diameters are greatly influenced by the development of the sacral curve. Taking the conjugate diameter of the pelvic brim as a unit for com- parison, the antero-posterior (dorso-ventral) and transverse diame- ters of the child and adult have the proportions shown in the table on the opposite page (Fehling). It will be seen from this that the general form of the pelvis in the new-born child is that of a cone, gradually^ diminishing in diameter from the brim to the outlet, a condition very different 488 POST-NATAL DEVELOPMENT from what obtains in the adult. Furthermore, it is interesting to note that sexual differences in the form of the pelvis are clearly distinguishable at birth; indeed, according to Fehling's obser- vations, they become noticeable "during the fourth month of intra- uterine development. Diameter New-bom Female Adult Female New-born Male Adult Male Conjugata vera I.OO 1. 19 0.96 1. 01 0.91 0.83 I.OO 1.292 1. 19 1. 151 I. OS I-I54 I.OO 1.20 o.gi 0.99 0.78 8d ^ Transverse 1.294 I 18 >. 1 Antero-Dosterior *> < U Transverse. > I. 14 1.07 T T C-7 *j 1 Antero-Dosterior O Transverse The upper epiphysis of the femur is entirely unossified at birth and consists of a cartilaginous mass, much broader than the rather slender shaft and possessing a deep notch upon its upper surface (Fig. 290). This notch marks off the great trochanter from the head of the bone, and at this stage of development there is no neck, the head being practically sessile. As development proceeds the inner upper portion of the shaft grows more rapidly than the outer portion, carrying the head away from the great trochanter and forming the neck of the bone. The acetabulum is shallower at birth than in the adult and cannot contain more than half the head of the femur; consequently the articular portion of the head is much less extensive than in the adult. It is a well-known fact that the new-born child habitually holds the feet with the soles directed toward one another, a position only reached in the adult with some difficulty, and associated with this supination or inversion there is a pronounced extension of the foot {i.e., flexion upon the leg as usually understood; see p. 104), it being difl&cult to flex the child's foot beyond a line at right angles with POST-NATAL DEVELOPMENT 489 the axis of the leg. These conditions are due apparently to the extensor and tibialis muscles being relatively shorter and the oppos- ing muscles relatively longer than in the adult, and with the elon^ gation or shortening, as the case may be, of the muscles on the assumption of the erect position, the bones in the neighborhood of the ankle-joint come into new relations to one another, the result being a modification of the form of the articular surfaces, especially of the talus (astragalus). In the child the articular cartilage of the trochlear surface of this bone is continued onward to a consid- erable extent upon the neck of the bone, which comes into contact Fig. 290. — Longitudinal Sections of the Head of the Femur of {A) New BORN Child and (B) a Later Stage of Development. with the tibia in the extreme extension possible in the child. In the adult, however, such extreme extension being impossible, the cartilage upon the neck gradually disappears. The supination in the child brings the talus in close contact with the inner surface of the calcaneus and with the sus tenaculum tali; with the alteration of position a growth of these portions of the calcaneus occurs, the sustentaculum becoming higher and broader, and so becoming an obstacle in the way of supination in the adult. At the same time a greater extent of the outer surface of the talus comes into contact with the lateral malleolus, with the result that the articular surface 490 LITERATURE is considerably increased on that portion of the bone. Marked changes in the form of the talo-navicular articulation also occur, but their consideration would lead somewhat further than seems desirable. LITERATURE C. Aeby: "Die Altersverschiedenheiten der menschlichen Wirbelsaule." Archiv fur Anat. und Physiol., Anat. Abth., 1879. W. Camerer: " Utersuchungen iiber Massenwachsthum und Langenwachsthum der Kinder," Jahrbuchfiir Kinder heilkunde, xxxvi, 1893. H. H. Donaldson: "The Growth of the Brain," London, 1895. H. Fehling: "Die^Form des Beckens beim Fotus und Neugeborenen und ihre Bezie- hung zu der beim Erwachsenen," Archiv fUr GynakoL, x, 1876, H. Friedenthal: "Das Wachsthum des Korpergewichtes des Menschen und anderer Saugethiere in verschiedenen Lebensaltern," Zeit. allgem. Physiol., DC, 1909. J. A. Hammar: "Ueber Gewicht, Involution und Persistenz der Thymus im Post- fotalleben des Menschen," Archiv jur Anat. und Phys., Anat. Abth., Supplement, 1906. W. Henke: "Anatomic des Kindersalters," Handbuch der Kinder krankheiten (Ger- hardt), Tubingen, 1881. C. Hennig: "Das kindliche Becken," Archiv fUr Anat. und Physiol., Anat. Abth., 1880. C. Huter: "Anatomische Studien an den Extremitatengelenken Neugeborener und Erwachsener," Archiv fiir patholog. Anat. und Physiol., xxv, 1862. W. Stephenson: "On the Relation of Weight to Height and the Rate of Growth in Man," The Lancet, 11, 1888. R. Thoma: " Untersuchungen iiber die Grosse und das Gewicht der anatomischen Bestandtheile des menschlichen Korpers," Leipzig, 1882. H. Vierordt: "Anatomische, Physiologische und Physikalische Daten und Tabel- len," Jena, 1893. H. Welcker: "Untersuchungen iiber Wachsthum und Bau des menschlichen Schadels," Leipzig, 1862. INDEX After-birth, 140 After-brain, 390 Age of embryos, 105 Agger, nasi, 179 Allantois, 112, 116, 364 Alveolo-lingual glands, 295 groove, 291 Amitotic division, 7 Amnion, iii, 112 Amniotic cavity, 57 Amphiarthrosis, 190 Amphiaster, 5 Angioblast, 222 Annulns of Vieussens, 235 Anterior commissure, 410 Anthelix, 450 Antitragus, 450 Anus, 283 Aortic arches, 245 bulb, 232 septum, 237 Archenteron, 51, 282 Archoplasm sphere, 4 Arcuate fibers, 394 Areas of Langerhans, 315 Arrectores pilorum, 149 Arteries, 241 anterior tibial, 255 aorta, 246 branchial, 243 carotid, 244 centralis retinae, 463 coeliac, 248 common iliac, 246, 252 costo-cervical, 251 dorsalis pedis, 256 epigastric, 251 external iliac, 249 maxillary, 244 Arteries, femoral, 255 hyaloid, 452 hypogastric, 249, 269 inferior gluteal, 256 inferior mesenteric, 248 innominate, 246 intercostal, 246 internal mammary, 251 maxillary, 244 spermatic, 247 interosseous, 252, 255 lingual, 244 lumbar, 246 median, 252 middle sacral, 247 peroneal, 256 popliteal, 255 posterior tibial, 255 profunda femoris, 255 pulmonary, 245 radial, 254 renal, 247 sciatic, 255 subclavian, 246, 252 superficial radial, 252 superior mesenteric, 248 vesical, 249 temporal, 244 ulnar, 252 umbilical, 119, 243, 248 vertebral, 249 vitelline, 224 Articular capsule, 190 Ary-epiglottic folds, 338 Arytenoid cartilages, 339 Aster, s Atresia of duodenum, 309 of pupil, 457 Atrial septum, 234 Atrio-ventricular bundle, 240 valves, 239 491 492 INDEX Auerbach, plexus of, 425 Auricle, 449 Axis cylinder, 382 B Bartholin, glands of, 367 Belly-stalk, 72, 116 Bile capillaries, 311 Bladder, 366 Blastoderm, 45 Blastopore, 51, 57. 59 Blastula, 42 Blood, 226 islands, 223 platelets, 230 vessels, 222 Body cavity, 62 Bone, development of, 156 growth of, 159 Bone-marrow, 158 Bones: atlas, 165, 167 axis, 167 carpal, 187, 190, 486 clavicle, 185, 486 coccyx, 168 conch ae, 178 epistropheus, 165, 167 ethmoid, 177 femur, 189, 487, 488 fibula, 189, 487 frontal, 180 humerus, 187, 486 hyoid, 184 ilium, 188, 487 incus, 182, 445 innominate, 188, 487 interparietal, 175 ischium, 188, 487 lachrymal, 180 malleus, 182, 445 mandible, 182 maxilla, 181 metacarpal, 188, 486 metatarsal, 190, 487 nasal, 180 Bones: occipital, 172, 17s palatine, 181 parietal, 180 patella, 189, 487 periotic, 171, 179 phalanges, 188, 190, 486, 487 precoracoid, 191 premaxilla, 181 pubis, i88, 487 radius, 187, 486 ribs, 164, 167 sacrum, 168, 482 scapula, 186, 486 sphenoid, 176 stapes, 446 sternum, 168 suprasternal, 169 tarsal, 189, 487, 488 temporal, 179 tibia, 189, 487 turbinated, 178 ulna, 187, 486 vertebrae, 162, 166, 483 vomer, 178 zygomatic, 180 Brachia conjunctiva, 398 Brain, 390, 480 Branchial arches, 93, 99 clefts, 93 epithelial bodies, 296, 297 fistula, 94 Branchiomeres, 84 Bronchi, 335 Bucconasal membrane, 285 Bulbo-urethral glands, 367 Bulbo-vestibular glands, 367 Burdach, fasciculus of, 389 Bursa omentalis, 327 Caecum, 304, 307 Calcar, 408 Canal, inguinal, 371 of Cloquet, 467 of Gartner, 361 of Nuck, 369 INDEX 493 Canal of Petit, 467 Canalized fibrin, 130 Capillaries, 224 Cartilages of Santorini, 339 of Wrisberg, 339 Caruncula lacrimalis, 472 Cauda equina, 388 Caul, 115 Cell, I, 3 division, s theory, i Centrosome, 4 Cerebellum, 396 Cerebral aqueduct, 399 convolutions, 407 cortex, 412 hemispheres, 404 peduncles, 398, 399 Charcot, crystalloid of, 14 Cheek groove, 293 Chin ridge, 103 Chondrioconts, 5 Chondriosomes, $ Chondrocranium, 172, 175 Chorda canal, 60 dorsalis, 78 endoderm, 78 Chorioid coat, 454, 467 plexus, 393, 401, 406 Chorioidal fissure of brain, 406 of eye, 452, 457 Chorion, 71, 121 frondosum, 127 laeve, 127 Chorionic villi, 1 26 Chromaflfine organs, 374 Chromatin, 4 Chromosomes, 5 reduction of, 15, 30 Ciliary body, 458 ganglion, 429 muscle, 469 Cleft palate, 286 sternum, 171 Clitoris, 367 Cloaca, 282, 363 Cloacal membrane, 283 Cloquet, canal of, 467 Coccygeal ganglion, 276 Ccelom, 51 62, 73, 81 Collateral eminence, 409 Colliculus seminalis, 362 Coloboma, 458 Colon, 306 Colostrum, 153 Conjunctiva, 469 Connective tissues, 155 Cornea, 453, 468 Corniculate cartilages, 338 Corona radiata, 21, 357 Coronary sinus^ 234, 260 Corpora mammillaria, 402 quadrigemina, 399 Corpus albicans, 24 callosum, 410 luteum, 23 striatum, 404 Corti, spiral organ of, 441 Cowper, glands of, 367 Cranial nerves, 414 sinuses, 257 Cricoid cartilage, 339 Cuneiform cartilages, 338 Cutis plate, 83 Cytoplasm, 3 Cyto-trophoblast, 57, 125 D Darwin's tubercle, 450 Decidua basalis, 132, 135 capsularis, 124, 133, 134 reflexa, 124, 133 serotina, 132 vera, 132, 133 Decidual cells, 134, 140 'Dendrites, 382 Dental groove, 287 papilla, 287 shelf, 287 Dentate gyrus, 408 Dermatome, 83 Descent of ovary, 369 of testis, 370 494 INDEX Diaphragm, 323 Diarthrosis, 191 Diencephalon, 390, 399 Discus proligerus, 20, 357 Double monsters, 49 Duct of Santo rini, 315 of Wrisberg, 315 Ductus arteriosus, 245, 269 Botalli, 245 choledochus, 310 cochlearis, 439 Cuvieri, 259 ejaculatorius, 359 endolymphaticus, 437 reuniens, 439 venosus, 262 Duodenum, 305, 306, 309 E Ear, 436 Ebner, glands of, 436 Ectoderm, 51 Embryo, age of, 105 external form, 89 growth of, 477 Embryonic disc, 57 Embryo troph, 125 Enamel organ, 287, 289 Enchylema, 4 Endocardium, 230 Endoderm, 51, 54, 57 Enveloping layer, 45, 48 Ependymal cells, 381 Epiblast, 51 Epibranchial placodes, 422 Epidermis, 143 Epididymis, 358 Epiglottis, 338 Epiphyses, 158 Epiphysis cerebri, 400 Epiploic foramen, 327 Episternal cartilages, 169 Epitrichium, 143 Eponychium, 147 Epoophoron, 360 Erythrocytes, 226, 227 Erythroplastids, 227 Eustachian tube, 296, 444 valve, 23s Extrauterine pregnancy, 23 Eye, 451 Eyelids, 469 Fallopian tubes, 361 Fasciculus communis, 419 of Burdach, 389 of Goll, 388 solitarius, 393, 419 Fenestra cochleae, 444 ovalis, 444 rotunda, 444 vestibuli, 444 Fertilization of ovum, 31 Fetal circulation, 267 Fibrinoid, 130 Fifth ventricle, 411 Filum terminale, 388 Fimbria, 410 ovarica, 362 Foliate papillae, 436 Fontana, spaces of, 469 Foramen caecum, 298 of Winslow, 327 ovale, 234, 241 Fore-brain, 390 Formatio reticularis, 394 Fornix, 410 Frontal sinuses, 178 Funiculus cuneatus, 389 gracilis, 388 Furcula, 296, 337 Gartner, canals of, 361 Gall bladder, 310 Ganglionated cord, 427 Gastral mesoderm, 53, 61 Gastrula, 51 Geniculate bodies, 401 Genital folds, 367 ridge, 341, 353 INDEX 495 Genital swelling, 367 tubercle, 367 Germ cells, 8 layers, 50, 63 plasm, 8 Giraldes, organ of, 358 Glands of Bartholin, 367 bulbo-urethral, 367 bulbo-vestibular, 367 of Cowper, 367 of Ebner, 436 Meibomian, 470 of Moll, 470 salivary, 293 tarsal, 470 Goll, fasciculus of, 388 Graafian follicle, 19 Great omentum, 327 Groove of Rosenmiiller, 297 Gubernaculum testis, 360 Gynsecomastia, 153 Haemoblasts, 222 Haematopoietic organs, 226 Haemolymph nodes, 275 Hairs, 148 Hare lip, 102, 182 Hassall's corpuscles, 300 Haversian canals, 160 Head cavities, 82 process, 59, 72 Heart, 230, 480 Helix, 450 Hensen's node, 59 Hermaphroditism, 369 Hind-brain, 390 Hippocampus, 408 Hyaloid canal, 467 Hydatid of Morgagni, 359 stalked, 362 Hydramnios, 115 Hymen, 362 Hyperthelia, 152 Hypertrichosis, 150 Hypoblast, 51 Hypochordal bar, 163 Hypophysis, 403 Hypospadias, 369 Hypothalamic region, 401 Idiochromosomes, 16, 34 Iliac lymph sac, 270 Implantation of ovum, 121 Infracardial bursa, 327 Infundibulum, 404 Inguinal canal, 371 Inner cell mass, 48 Insula, 409 Interarticular cartilages, 191 Intercarotid ganglion, 377 Intermediate cell mass, 80 Interrenal organs, 374 Interventricular foramen, 405 Intervertebral fibro-cartilage, 162, 164 Intestine, 304, 481 Iris, 458 Isthmus cerebri, 390, 398 Jacobson, organ of, 434 Joints, 190 Jugular lymph sac, 270 K Karyokinesis, 7 Karyoplasm, 3 Kidney (see Metanephros), 347, 48c L Labia majora, 368 minora, 368 Lachrymal gland, 471 Lamina terminalis, 402 Langerhans, areas of, 315 Langhans cells, 129 Lanugo, 149 Larynx, 337 Lateral thyreoids, 301 Lens, 452, 454 496 INDEX • Lesser omentum, 326 Leukocytes, 229 Ligaments: broad, of uterus, 352, 360 coraco-humeral, 217 coronary, of liver, 324 falciform, of liver, 324 fibular lateral, of knee, 201 flavan, 164 inguinal, 353, 360, 362 interspinous, 164 mucosum, 192 of the ovary, 362 pectinatum iridis, 469 round, of liver, 270 round, of uterus, 362 sacro-tuberous, 201 spheno-mandibular, 184 suspensory of lens, 466 Limbs, 93, 103 Lip-ridge, 103 Lips, 286 Liver, 309, 480 Lubarsch, crystalloid of, 14 Lungs, 334, 481 Luschka's ganglion, 276 Lymphatics, 270 Lymph nodes, 273 sacs, 270 Lymphocytes, 229, 276 M Magma, cellular, 68 reticular, 70 Mammary gland, 150 Mandibular process, 94 Mastoid cells, 447 Maturation of ovum, 28 Maxillary antrum, 178 process, 94 Meckel's cartilage, 173, 182 diverticulum, 116, 307 Mediastina, 325 Medulla oblongata, 390 Medullary canal, 77, 90 cords, 356 Medullary folds, 75 groove, 73 sheath, 386 Megacaryocytes, 230 Meibomian glands, 470 Meissner, plexus of, 425 Membrana pupillaris, 457 reuniens, 84 tectoria, 442 Membrane bone, 156 Menstruation, 26 Mesencephalon, 390, 398 Mesenchyme, 64 Mesenteriole, 330 Mesentery, 326 Mesocardium, 319 Mesocolon, 328 Mesoderm, 51 somatic, 80 splanchnic, 81 ventral, 80 Mesodermic somites, 75, 79 Mesogastrium, 326 Mesonephros, 345, 358 Mesorchium, 359, 371 Mesothelium, 64 Metamere, 86 Metanephros, 347 Metencephalon, 390, 395 Mid-brain, 390 Middle ear, 444 Milk ridge, 150 Mitochondria, 5 Mitosis, 7 Moll, glands of, 470 Montgomery's glands, 151 Morgagni, hydatid of, 359 Morula, 46 Mouth cavity, 285 Miillerian duct, 351 Muscle plates, 83 Muscles: arrectores pilorum, 149 biceps femoris, 217 branchiomeric, 207 chondroglossus, 211 ciliary, 469 INDEX 497 Muscles: coccygeus, 206 constrictor of pharynx, 209, 301 cranial, 206 curvator coccygis, 206 depressors of hyoid, 203 digastric, 209 dilatator iridis, 459 dorsal, 202 eye, 207 facial, 209 gastrocnemius, 215, 219 geniohyoid, 203 genioglossus, 203 glosso-palatinus, 209 hyoglossus, 204 hyposkeletal, 204 intercostal, 204 laryngeal, 209, 340 latissimus dorsi, 200, 216 levator ani, 206 limb, 211 longus capitis, 204 colli, 204 lumbrical, 219 masseter, 209 mylohyoid, 209 obliqui abdominis, 204 occipito-f rental is, 201, 209 omohyoid, 200 pectorals, 216 perineal, 206 peroneus longus, 217 platysma, 209 pronator quadratus, 217 psoas, 204 pterygoids, 209 pyramidalis, 203 rectus abdominis, 201, 203 sacro-spinalis, 201, 204 scaleni, 204 serrati posteriores, 201 serratus anterior, 201, 216 skeletal, 199 soleus, 215, 219 sphincter ani, 206 sphincter cloacae, 206 32 Muscles: sphincter cloacae, 206 iridis, 459 stapedius, 209, 446 sternohyoid, 200 sterno mastoid, 200, 204, 211 styloglossus, 204 stylohyoid, 209 stylopharyngeus, 209, 301 temporal, 209 tensor tympani, 209, 445 veli palati, 209 transversus abdominis, 204 thoracis, 204 trapezius, 200, 204, 211 Muscle tissue, 195 Myelencephalon, 390, 393 Myelin, 386 Myelocytes, 229 Myoblasts, 197 Myocardium, 230 Myotome, 83, 199 N Nails, 14s Nape bend, 93 Nasal pit, 10 1 process, loi Naso-lachrymal duct, 471 Nephrogenic cord, 346 Nephrostome, 344 Nephrotome, 83 Nerve components, 415, 418, 421 roots, 384 Nerves: auditory, 420 cranial, 414 hypoglossal, 417 olfactory, 433 optic, 462 recurrent, 340 spinal, 413 accessory, 421 splanchnic, 429 terminal, 417 Nerve tissue, 381 Neural crest, 384 498 INDEX Neurenteric canal, 6i, 73, 76 Neuroblasts, 382 Neuroglia cells, 382 Neuromeres, 423 Neurone theory, 386 Nitabuch's stria, 139 Non-sexual reproduction, 9 Normoblasts, 227 Notochord, 77 Nuck, canal of, 369 Nucleoli, 4 Nucleus, 3 Odontoblasts, 290 (Esophagus, 301 (Estrus, 28 Olfactory lobes, 41 1 organ, 433 Olivary body, 394 Omentum, 327 Oocyte, 29 Optic cup, 452, 457 recess, 402 Oral fossa, 91, loi, 282 Organ of Giraldes, 358 of Jacobson, 434 of Rosenmiiller, 360 Organs, 3 chromafline, 374 interrenal, 374 of taste, 435 of Zuckerkandl, 378 suprarenal, 374, 480 Osteoblasts, 156 Osteoclasts, 160 Otocyst, 437 Otic ganglion, 429 Ovary, 356 descent of, 369 Ovulation, 22, 26 Ovum, 19 fertilization of, 31 implantation of, 121 maturation of, 28 segmentation of, 41 Palate, 285 Pancreas, 314, 481 Paradidymis, 358 Paraphysis, 400 Parathymus, 301 Parathyreoid bodies, 299 Paroophoron, 360 Parotid gland, 293 Parovarium, 360 Parthenogenesis, 9 Penis, 368 Pericardial cavity, 320, 321 Perineal body, 366 Perionyx, 147 Periosteum, 157 Periotic capsule, 171, 178 Peritoneum, 326 Petit, canal of, 467 Pfliiger's cords, 356 Pharyngeal bursa, 296 membrane, 282 tonsil, 296 Pharynx, 296 Pharyngo-palatine arches, 285 Pineal body, 400 Pinna, 450 Pituitary body, 403 Placenta, 135, 140 accessory, 127 deciduate, 140 embryotrophic, 126 haematrophic, 126 indeciduate, 140 praevia, 136 Placentar infarcts, 139 Plasmodi-trophoblast, 57, 125 Plasmodium, 125 Pleurae, 325 Pleuro-peritoneal cavity, 81, 322 Plica semilunaris, 470 Polar globules, 30 Polycaryocytes, 230 Polymastia, 152 Polyspermy, 35 Pons, 395 flexure, 392 INDEX 499 Post-anal gut, 283 Post-natal development, 466 Precaudal recess, 283 Precoracoid, 191 Prepuce, 368 Primitive groove, 59, 72 streak, 53, 72 Processus globularis, loi Pronephric duct, 342 Pronephros, 342 Pronuclei, 32 Prooestrum, 28 Prostate gland, 365 Prostomial mesoderm, 53, 61 Protoplasm, 2 Pro to vertebrae, 80 Rathke's pouch, 287, 403 Rauber's covering layer, 48 Rectum, 283 Red nucleus, 399 Reduction of chromosomes, 15, 30 Restiform body, 395 Rete cords, 353 ovarii, 357 testis, 356 Retina, 460 Retroperitoneal lymph sac, 270 Rhinencephalon, 412 RosenmtiUer, groove of, 297 organ of, 360 Sacculus, 439 Sacral bend, 93 Salivary glands, 293 Santorini, cartilages of, 339 duct of, 315 Sarcode, i Scala tympani, 444 vestibuli, 443 Sclerotic coat, 454, 467 Sclerotome, 83 Scrotum, 368 Sebaceous glands, 149 Segmentation nucleus, 32 of ovum, 41 Semicircular ducts, 438 Semilunar valves, 240 Seminiferous tubules, 356 Septum aortic, 237 pellucidum, 411 primum, 234 secundum, 234 spurium, 234 transversum, 321, 323, 327 ventricular, 237 Sertoli cells, 14 Sex cells, 353 cords, 353 Sexual reproduction, 9 Sinusoid, 225 Sinus, coronary, 234, 260 pocularis, 359 praecervicalis, 100 terminalis, 224 venosus, 232 Situs inversus viscerum, 49 Skin, 143, 481 Skull, 171, 483 Socia parotidis, 293 Solitary fasciculus, 393, 419 Somatic cells, 8 Spaces of Fontana, 469 Spermatic cord, 371 Spermatid, 14 Spermatocyte, 14 Spermatogenesis, 13 Spermatogonia, 14 Spermatozoon, 11 Sphenoidal cells, 178 Spheno-palatine ganglion, 429 Spinal cord, 387, 480 nerves, 413 Spiral organ of Corti, 441 Spleen, 275, 480 Stomach, 302 Sublingual ganglion, 429 gland, 295 Submaxillary ganglion, 429 Submaxillary gland, 294 Substance islands, 223 500 INDEX Sudoriparous glands, 150 Sulcus Monroi, 399 Superfetation, 37 Suprabranchial placodes, 422 Suprarenal bodies, 374, 480 accessory, 376 Supratonsillar fossa, 297 Suture, 190 Sympathetic nervous system, 423 Synchondrosis, 190 Syncytium, 125 Systems, 3 Tail filament, 96 Tarsal glands, 470 Taste, organs of, 435 Teeth, 287 Tegmentum, 398 Telencephalon, 390, 402 Testis, 354 descent of, 369 Thalami, 401 Thebesian valve, 235 Thoracic duct, 272 Thymus gland, 299, 480 Thyreoid cartilage, 338 gland, 298, 480 Thyreo-glossal duct, 298 Tissues, 3 Tongue, 291 Tonsils, 297 Touch, organs of, 435 Trachea, 337 Tragus, 450 Trophoblast, 57 Tuba auditiva, 444 Tubae uterinae, 361 Tuber cinereum, 402 Tuberculum impar, 291 Tubuli recti, 356 Tunica albuginea, 354, 356 vaginalis testis, 371 vasculosa lentis, 457 Tween-brain, 390 Twin-development, 48 Tympanic cavity, 444 membrane, 448 U Ultimo-branchial bodies, 301 Umbilical cord, 95, 119 Umbilicus, 90 Urachus, 118, 364 Ureter, 348 Urethra, 365 Urogenital sinus, 364 Uterovaginal camil, 353 Uterus, 361, 363 masculinus, 359 Utriculus, 439 prostaticus, 359 Vagina, 361, 363 Vaginal process, 369 Vallate papillae, 435 Vas deferens, 359 Veins: anterior cardinal, 256 tibial, 267 ascending lumbar, 266 azygos, 266 basilic, 267 cephalic, 266 emissary, 260 external jugular, 260 hemiazygos, 266 hepatic, 263 inferior vena cava, 265 innominate, 259 internal jugular, 256 jugulo-cephalic, 267 limb, 266 long saphenous, 267 portal, 262 posterior cardinal, 256, 260 primary fibular, 267 ulnar, 266 pulmonary, 235, 267 renal, 265 INDEX 501 Veins : subcardinal, 263 superior vena cava, 259 supracardinal, 265 suprarenal, 265 umbilical, 121, 262 vitelline, 224, 261 Velum, anterior, 398 interpositum, 400 marginal, 381 posterior, 393 Vena capitis, 256 Ventricular septum, 237 Vermiform appendix, 307 Vernix caseosa, 115, 149 Vertex bend, 90 Vesicula seminalis, 359 Vieussens, annulus of, 235 Villi, chorionic, 126 intestinal, 308 Vitreous humor, 454, 465 Vulva, 368 W Wharton's jelly, 121 Winslow, foramen of, 327 Wirsung, duct of, 315 Witch milk, 153 Wolfl&an body, 342, 358 duct, 342, 358 ridge, 341 Wrisberg, cartilage of, 339 Yolk sac, 89, no, 115 stalk, 89, 93, no Zona pellucida, 21 Zuckerkandl, organ of, 378 DATE DUE SLIP UNIVERSITY OF CALIFORNIA MEDICAL SCHOOL LIBRARY THIS BOOK IS DUE ON THE LAST DATE STAMPED BELOW Tlw. ;n, i]g2b 2 192e' Library of the University of California Medical School and Hospitals