Book - Embryology of the Pig

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Patten BM. Embryology of the Pig. (1951) The Blakiston Company, Toronto.

Online Editor

This historic 1951 embryology of the pig textbook by Patten was designed as an introduction to the topic. Currently only the text has been made available online, figures will be added at a later date. My thanks to the Internet Archive for making the original scanned book available. By the same author: Patten BM. The Early Embryology of the Chick. (1920) Philadelphia: P. Blakiston's Son and Co. Patten BM. Developmental defects at the foramen ovale. (1938) Am J Pathol. 14(2):135-162. PMID 19970381 Modern Notes pig

Historic Disclaimer - information about historic embryology pages

Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Embryology of the Pig

Frontispiece

Reconstruction (X 17.5) showing the organ systems of a 9.4 mm. pig embryo. For explanation see figures 60 and 66.

By BRADLEY M. PATTEN

Professor of Anatomy in the University of Michigan Medical School

THIRD EDITION

WITH COLORED FRONTISPIECE

AND 186 ILLUSTRATIONS IN THE TEXT (CONTAINING 412 FIGURES) OF WHICH 6 ARE IN COLOR

Philadelphia : THE BLAKISTON COMPANY : Toronto

Third Edition

Copyright, October 1948, by The Blakiston Company

BY P. Blakiston ’s Son & Co.

Copyright, 1951, by P Blakiston’s Son & Co , Inc.

Preface to Third Edition

In making the revision for a new edition of this book it did not seem desirable essentially to change its form or scope. Effort has been concentrated on improving the presentation of the original subject matter and bringing it up to date, rather than on its expansion. The entire book has been reset to a greater page width which has permitted enlarging certain of the illustrations that, in earlier editions, had proved to be too greatly reduced. With the generous cooperation of the publishers several of the important plates on the cardiovascular system have been remade to a larger scale and with color. A number of new illustrations have been drawn for sections where experience has shown that students needed additional graphic assistance in interpreting their laboratory material. It is hoped that these changes will all contribute toward making the book as a whole more serviceable.

Bradley M. Patten

August 1048

Preface to First Edition

This book represents an endeavor to set forth in brief and simple form the fundamental facts of mammalian development. The thread of the story and the illustrations have been based on pig embryos because of their value and availability as laboratory material. But special stress has been laid on the embryological phenomena involved instead of on the details of specific conditions existing in the pig. Throughout the book, every efTort has been made to present developmental processes as dynamic events with emphasis on their sequence and significance, rather than as a series of still pictures of selected stages.

Obviously no book can deal fully with all phases of development, even in a single form, and still remain serviceable as a text. As this book is for the student, it has seemed expedient, for the sake of clearness and simplicity, to omit many things which I should like to have included. My primary aim has been to write an account in which the essentials stand out adequately interpreted and unobscured by a multiplicity of details — to lay a foundation which can be further built upon in accordance with special needs or individual desires.

Bradley M. Patten

January 1927

Acknowledgment

The pleasantest thing about working on this book has been the generous aid I have received from many sources. Throughout the preparation of the initial edition the encouragement, criticism, and suggestions of my colleagues, Dr. F. C. Waite and Dr. S. W. Chase, were of the greatest help. In the preparation of material and in making the illustrations for the first edition the beautifully accurate work of Miss Kathryn Toulmin was of inestimable value. In making the new drawings added in the third edition I was fortunate in securing the unusually able assistance of Mrs. Dorothy Van Eck.

Dr. G. L. Streeter and Dr. C. H. Heuser of the Carnegie Institute allowed me free use of their extensive collection of young embryos and generously gave me many photographs made from their material. To Mrs. Charles S, Minot I am indebted for permission to use several figures from the late Professor Minot’s works. The accrediting in the figure legends of these and other borrowed illustrations by no means covers my obligation to other writers. Practically the entire bibliography is a statement of indebtedness for information and ideas.

I wish I might acknowledge individually the helpful services rendered by many of my students, but they are too numerous. Several reconstructions which I have used directly or indirectly have been largely their work. Of even greater assistance have been their suggestions during the shaping of the work — suggestions of especial value because they were made from a point of view difficult for an instructor to appreciate without such aid.

To The Blakiston Company, I am indebted for much helpful cooperation and especially for their liberality with regard to the number and quality of the illustrations.

No person other than my wife could have deciphered and put into usable form manuscript of the character I frequently turned over to her for revision and typing. Without her generous help the preparation of the text would have been much more arduous and long delayed.

Bradley M. Patten

Chapter 10

Tke Development of tke Urogenital System

The excretory and reproductive systems are so closely related both anatomically and embryologically that they must inevitably be considered together. Neither system is particularly simple in organization and the two of them together present quite a formidable array of structures. Naturally the development of such a composite group involves much of special interest to the embryologist. We shall see organs formed by the association of parts which arise independently at different places. Certain organs appear and then disappear completely without ever having become functional. Other organs fall into disuse in their original capacity and begin to degenerate only to have some part seized upon and salvaged by a new organ for a new function. We have, as it were, in the story of the development of these systems many characters. Each character, individually, is doing things of interest. Sooner or later their activities cross. The method of the novelist in dealing with such a situation would be to switch from one character to another to keep us in confusion and suspense as to what is going to happen next. Our method in dealing with this embryological story must be exactly the reverse. To prevent the various threads of the story from becoming entangled we must, as far as possible, follow one group of structures from their origin to their completion before becoming involved with another. Because the , excretory system appears earlier than the reproductive system, we shall take it up first and follow it through. Then we must return to young embryos and pick up the story of the internal reproductive system, watching constantly its relations to that of the excretory system with which we have already become familiar. Yet again we must go back and follow the differentiation of the external genitalia. Any attempt to develop all the threads of the story synchronously would lead only to confusion.

I. The Urinary System

The General Relationships of Pronephros, Mesonephros, and Metanephros. As a preface to the account of the development of the

198

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

excretory organs in the pig, it is desirable to review certain facts about the structure and development of the excretory organs in the vertebrates generally. Without such information as a background the story of the early stages of the formation of these organs in a mammal seems utterly without logical sequence. With it, the progress of events encountered in mammalian development seems but natural, because it is so clearly an abbreviated recapitulation of conditions which existed in the adult stages of ancestral forms.

There occur in adult vertebrates three distinct excretory organs. The most primitive of these is the pronephros which exists as a functional excretory organ only in some of the lowest fishes. As its name implies, the pronephros is located far cephalically in the body. In all the higher fishes and in the Amphibia the pronephros has degenerated and its functional role has been assumed by the mesonephros, a new organ located farther caudally in the body. In birds and mammals a third excretory organ develops caudal to the mesonephros. This is the metanephros or permanent kidney. All three of these organs are paired structures located retroperitoneally in the dorsolateral body-wall. Each consists essentially of a group of tubules which discharge by way of a common excretory duct. In the different nephroi the tubules vary in structural detail but their functional significance is, in all cases, much the same. They are concerned in collecting waste material from the capillary plexuses associated with them and excreting it from the body.

In the development of the urinary system of birds and mammals, pronephros, mesonephros, and metanephros appear in succession, furnishing an excellent epitome of the same evolutionary hi^ory which may be learned in more detail from comparative anatomy. In embryos sufficiently young we find only the pronephros established. It consists of a group of tubules emptying into ducts, called the pronephric ducts, which discharge into the cloaca (Fig. 114, A).

A little later in development there arises in close proximity to each pronephric duct a second group of tubules more caudal in position than the pronephros. These are the mesonephric tubules. In their growth they extend toward the pronephric ducts and soon open into them (Fig. 114, B). Meanwhile the pronephric tubules begin to degenerate and the ducts which originally arose in connection with the pronephros are appropriated by the developing mesonephros. After the degeneration of the pronephric tubules these ducts lose their original name and are called mesonephric ducts because of their new associations (Fig. 114, C).

THE URINARY SYSTEM

. 199

At a considerably later stage outgrowths develop from the mesonephric ducts near their cloacal ends (Fig. 114, C). These outgrowths form the ducts of the metanephroi. They grow cephalo-laterad and eventually connect with a third group of tubules which constitute the metanephros (Fig. 114, D). With the establishment of the metanephroi or permanent kidneys, the mesonephroi begin to degenerate. The only parts of the mesonephric system to persist, except in vestigial form, are some of the ducts and tubules which, in the male, are appropriated by the testis as a duct system (Fig. 114, D, right).

The Pronephros. In the embryos of birds and mammals the pronephros is an exceedingly transitory structure. Very young embryos show rudimentary proncphric tubules arising from the

Fig. 114 . Schematic diagrams to show the relations of pronephros, mesonephros, and metanephros. (Patten: ‘‘Early Embryology of the Chick,” The Blakiston Company.)

200

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

intermediate mesoderm opposite a few of the somites lying well cephalically in the body. (Birds, usually 5th to 16th somites; mammals, usually 6th to 14th somites.) The significance of these vestigial tubules can readily be understood by comparing them with a plan of the fully developed and functional pronephric tubules of which they are a sketchy recapitulation (Fig. 115, A, B).

The pronephric duct arises at the level of the pronephric tubules by the extension caudad of the distal end of each tubule till it meets and fuses with the tubule behind it to form a continuous channel. The

Fig. 115. Drawings to show structure of nephric tubules.

A, Pronephric tubule from section through 12th somite of a 16-somite chick embryo. (After Lillie.)

B, Diagram of functional pronephric tubule. (After Wiedersheim.)

C, Primitive mesonephric tubule with rudimentary nephrostome, from section through 17th somite of 30-somite chick embryo.

D, Schematic diagram of functional mesonephric tubule of the primitive type which retains the nephrostome. (After Wiedersheim.)

THE URINARY SYSTEM

201

Dorsal

Laterai^< J â–º Mesial

Ventral

Fig. 116. Drawings showing the development of the mesonephric tubules in the pig. (Based on figures by McCallum and Lewis.) Abbreviation: T, mesonephric tubule.

duct thus estal^lished continues to grow caudad beyond the level of the tubules until it eventually opens into the cloaca (Fig. 114). Since the pronephric tubules never become functional in mammalian embryos, we need give them no further consideration. The pronephric duct, however, becomes of importance through its subsequent relations to the mesonephros.

The Mesonephros. The mesonephros in young mammalian embryos attains a high degree of development. In the pig it is especially large, being one of the most conspicuous organs in the embryo (Figs. 59 and 60). Its tubules become highly differentiated and, pending the development of the metanephros, are believed to play an active part in the embryo’s elimination of nitrogenous waste.

As was the case with the pronephric tubules, the mesonephric

202

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

tubules are derived from the intermediate mesoderm. At the time the tubules arise from it the intermediate mesoderm shows no trace of segmentation. When viewed in reconstructions or dissections showing its longitudinal extent, it appears as a continuous band connecting the somites with the lateral mesoderm. For this reason it is sometimes spoken of as the nephrogenic cord. When the mesonephric tubules are first budded off from the intermediate mesoderm they appear as cell clusters very close to, but not in contact with, the mesonephric (old pronephric) duct (Fig. 116, A). Once the process of tubule formation starts, the nephrogenic tissue is soon completely converted into young tubules, three or four tubules being formed opposite each somite from about the 14th to the 32nd.

The newly formed tubules grow rapidly, extending toward the mesonephric duct with which they soon attain connection (Fig. 116, B). In birds a few of the more cephalic tubules show a rudimentary nephrostome opening to the coelom, a condition comparable to that in some of the lower forms in which the mesonephros is the adult functional kidney (Fig. 115, C, D). Most if not all of the tubules in the mammalian mesonephros slur over this phase in recapitulation

somite

neural tube>J

notochord/

dorsal aorta afferent vessel glomerulus efferent vessel

^ mesonephric duct

subcardinal

vein

posterior

cardinal vein

collecting vein connecting sulvand post* cardinals

capsule

Fig. 117. Diagrams showing the relations of the blood vessels to a mesonephric tubule. (Based on figures by McCallum.)

THE URINARY SYSTEM

203

and develop without a nephrostome (Figs. 116 and 117). Having no ciliated nephrostome capable of drawing in coelomic fluid, such tubules obtain their liquid content from the glomerular capillaries (Fig. 117). This fluid serves to carry off by way of the mesonephric duct waste materials from the blood stream. The discarding of the nephrostome by the more specialized of the mesonephric tubules is an interesting step toward the still more highly differentiated tubule we shall encounter in the metanephros.

After they have attained connection with the duct, the mesonephric tubules elongate rapidly. Starting from a simple S-shaped configuration, their pattern is complicated by a series of secondary bendings (Fig. 116, C, F). This growth in length greatly increases their surface exposure, thereby enhancing their capacity for interchanging materials with the blood in the adjacent capillaries.

The relations of the mesonephric tubules to the vascular system are indicated schematically in figure 117. The mesonephros is fed by many small arteries arising ventro-laterally from the aorta. Each of these arterial twigs pushes into the dilated free end of a developing tubule, forming from it a double-walled cup called a glomerular (Bowman’s) capsule (Fig. 117, B). Within the capsule the artery breaks up into a knot of capillaries known as the glomerulus. Blood from the glomerulus leaves the capsule over one or more vessels (efferent with reference to the glomerulus) which again break up into capillaries. This time the capillaries form a plexus in close relation to the body of the tubule in its tortuous course from glomerulus to duct. From these capillaries the blood passes to collecting veins which are for the most part peripherally located in the mesonephros and more or less circularly disposed about it (Fig. 1 17, A). These collecting veins form a freely anastomosing system connecting both with the posterior cardinals and the subcardinals through which the blood is eventually returned to the general circulation.

Although it is relatively more conspicuous earlier in development, the mesonephros does not attain its greatest actual bulk until the embryo has reached a size of about 60 mm. When the metanephros becomes well developed, the mesonephros undergoes rapid involution and ceases to be of importance in its original capacity. In dealing with the reproductive system, however, we shall see that its ducts and some of its tubules still persist and give rise to structures of vital functional importance.

THE URINARY SYSTEM

205

The Metanephros. The metanephros has a dual origin. It arises in part from the mesonephric duct, and in part from the intermediate mesoderm. Of these separate primordia the diverticulum arising from the mesonephric duct is the first to appear. In embryos as small as 5 or 6 mm. this metanephric diverticulum can usually be identified as a tiny bud-like outgrowth just cephalic to the point where the mesonephric duct opens into the cloaca (Fig. 118, A). Almost from its first appearance the blind end of the metanephric diverticulum is dilated, foreshadowing its subsequent enlargement to form the lining of the pelvis of the kidney. The portion of the diverticulum near the mesonephric duct remains slender, presaging its eventual fate as the duct draining the kidney {ureter).

As the metanephric diverticulum pushes out, it collects about its distal end mesoderm which has arisen from the nephrogenic cord of intermediate mesoderm caudal to the mesonephros. The original relations of this mass of mesoderm are soon entirely lost because it becomes closely massed about the pelvic end of the metanephric diverticulum and pushed farther and farther away from its point of origin as the diverticulum continues to grow ccphalad (Figs. 118, 119, and 120). This mesoderm gives rise to the secretory tubules of the metanephros or permanent kidney, and is, therefore, often designated as metanephrogenous tissue.

While the metanephric primordium is being pushed cephalad, it is increasing rapidly in size and encroaching on the space occupied by the mesonephros. Coincidently, rapid internal differentiation is progressing. The pelvic end of the diverticulum expands within its investing mass of mesoderm and takes on a shape suggestive of the pelvic cavity of the adult kidney (Figs. 119 and 120). From this primitive pelvic dilation arise numerous outgrowths which push radially into the surrounding mass of nephrogenic mesoderm (Fig. 138). These outgrowths become hollow, forming ducts which branch and rebranch as they extend toward the periphery. These are the collecting ducts of the kidney {straight collecting tubules) (Fig. 119, E).

The first changes in the mesoderm which presage the formation of the uriniferous tubules, occur near the distal ends of terminal branches of the collecting ducts. The mesodermal cells become arranged in small vesicular masses which lie in close proximity to the blind end of the collecting duct (Fig. 121, A). Each of these vesicular cell masses is destined to become a uriniferous tubule draining into the duct near which it arises. (In figure 121, A, this condition is

206

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

Fig. 119, Diagrams showing a series of stages in the growth and differentiation of the metanephric diverticulum. (Patten. ‘'Human Embryology,” The Blakiston Company.)

represented schematically, only two uriniferous tubules being shown in relation to the end of the collecting ducts whereas there are actually several. The tubule on the right is represented as slightly further differentiated than that on the left.) As the developing tubules extend toward the end of the collecting duct, the bud-like tips of the duct itself grow out to meet them (Fig. 121, B). Soon the two become confluent (Fig. 121, C). In this stage the metanephric tubules are very similar to young mesonephric tubules (cf. Fig. 116). In their later development the metanephric tubules become much more elaborately convoluted than the mesonephric but their functional significance is the same.

As the kidney grows in mass additional generations of tubules are formed in its peripheral zone. New orders of straight collecting tubules arise from buds, called ampullae, which appear at about the point where the excretory tubules become confluent with the straight collecting tubules of the previous order (Fig. 121, D). At the tips of the new straight collecting tubules a new order of excretory tubules is formed from the metanephrogenous tissue in the same manner that

THE URINARY SYSTEM

207

Neural tube

Notochord _ .

Sacral ,

symp. plexus ^

Mesonephros Metanephros Metonep hric duct

Mesonephric duct

Allantoic art.

Bose of Morn of' allontois urogenitol sinus Urogenital sinus

Urethral groove in genital tubercle

Post.

cardinal vein Allantoic art.

Caudal pole of metanephros Metonephric duct (cut twice)

Coelom Mesorectum Anal orifice

Posterior appendage bud

Fig. 120. Drawings (X 15) of transverse sections through the pelvic region of a 15 mm. pig embryo. The level of each section is indicated on the inset lateral plan.

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

Loop of Henie

Fio. 121. Diagrams showing the development of the mctanephric tubules of mammalian embryos. (After Huber, from Kelly and Burnarn: “Diseases of Kidneys, Ureters, and Bladder,'’ courtesy, D. Appleton-Uentury Co.)

the previous group was formed. This process is repeated many times during the growth of the kidney, about 12 to 14 generations of tubules usually having made their appearance by the time of birth. Some additional generations of tubules may be formed in the period of rapid growth immediately following birth but most of the postnatal growth of the kidneys, by which they keep pace with increased body mass, is due to the growth of the tubules rather than to further increase in their number.

The blood supply to the metanephros, instead of coming directly from the aorta by numerous small branches as is the case in the mesonephros, is brought in from the aorta through the renal artery and thence distributed by a very elaborate system of smaller vessels. Nevertheless the relations of the smaller vessels to the tubules are essentially alike in the two organs. An arterial twig breaks up into a glomerulus within a capsule at the distal end of each tubule. An

THE URINARY SYSTEM

209

efferent vessel leaves the glomerulus to break up again in a meshwork of capillaries in close relation to the tortuous tubule. Collecting veins return the blood to the general circulation, freed of the nitrogenous waste matter which is a constant by-product of metabolism.

Formation of the Bladder and Early Changes in the Cloacal Region. In dealing with the development of the extra-embryonic membranes we have already taken up the formation of the allantois as an evagination from the caudal end of the primitive gut (Fig. 37). Shortly after this occurs, the gut caudal to the point of origin of the allantois becomes enlarged to form the cloaca (Fig. 118, A). When the cloacal dilation is first formed, the hind-gut still ends blindly, but there is an ectodermal depression under the root of the tail which has sunk in toward the gut until the tissue separating the gut from the outside is very thin (Fig. 37, D). This ectodermal depression is known as the proctodaeum and the thin plate of tissue still closing the hindgut is called the cloacal membrane. Eventually the cloacal membrane ruptures, establishing a caudal outlet for the gut. This rupture is similar to the rupture of the oral plate which has previously established communication between the stomodaeum and the cephalic end of the primitive gut.

Before this occurs important changes take place internally. The cloaca begins to be divided into two parts, a dorsal part which forms the rectum and a ventral part, the urogenital sinus (Fig. 122). This division is effected by the growth of the urorectal Jold., a crescentic fold which cuts into the cephalic part of the cloaca where the allantois and the gut meet (Fig. 122). The two limbs of the fold bulge into the lumen of the cloaca from either side, eventually meeting and fusing with each other! The progress of this partitioning fold toward the proctodaeal end of the cloaca makes it difficult to keep track of the original limits of the allantois, since as the urogenital sinus is lengthened, it is, in effect, added onto the allantois (cf. Fig. 118, A~D). The point of entrance of the mesonephric ducts, however, affords a landmark which is sufficiently accurate for all practical purposes. Before the urorectal fold has changed the relations, the mesonephric ducts open from either side into the cephalic part of the cloaca. After the urorectal fold has divided the cloaca, the mesonephric ducts appear to empty into the allantois (Fig. 122). This gives us our bearings, for the mesonephric ducts are actually opening into the newly established urogenital sinus which is continuous with the allantois.

Before the cloacal membrane ruptures, separation of the cloaca is

210

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

Fig. 122. Schematic ventro-latcral view of the urogenital organs of a young mammalian embryo. (Redrawn from Kelly and Burnam, ‘'Diseases of Kidneys, Ureters and Bladder,” courtesy, D. Appleton-Century Co.) The figure as originally drawn was based on human embryos of 12 to 14 mm. In all essentials the relations shown are applicable to 14 to 15 mm. pig embryos.

complete and its two parts open independently. The opening of the rectum is the anus and that of the urogenital sinus is the ostium urogenitale (Fig. 118, D).

Meanwhile the proximal part of the allantois has become greatly dilated and may now quite properly be called the urinary bladder. We should remember, however, that the neck of the bladder has been formed largely from tissue which was originally part of the cloaca.

In the growth of the bladder the caudal portion of the mesonephric duct is absorbed into the bladder wall. This absorption progresses until the part of the mesonephric duct caudal to the point of origin of the metanephric diverticulum has disappeared. The end result of this process is that the mesonephric and metanephric ducts open independently into the urogenital sinus. The metanephric duct,

THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 211

possibly due to traction exerted by the kidney in its migration headwards, acquires its definitive opening somewhat laterally and cephalically to that of the mesonephric duct. It then discharges into the part of the urogenital sinus which was incorporated in the bladder. The mesonephric ducts open into the part of the urogenital sinus which remains narrower and gives rise to the urethra (Fig. 118, D-F). The urethra acquires quite diflferent relations in the two sexes. It is, therefore, desirable to defer consideration of it and take it up in connection with the external genitalia.

II. The Development of the Internal Reproductive Organs

The Indifferent Stage. One of the striking things in the development of the reproductive system is the condition which at first exists as to sexual differentiation. One might expect that reproductive mechanisms as totally unlike as those of adult males and females would be sharply differentiated from one another from their earliest appearance. Such is not the case. Young embryos exhibit gonads which at first give no evidence as to whether they are destined to develop into testes or ovaries. Along with these neuter or indifferent gonads there are present in an undeveloped state two different duct systems. If the individual develops into a female, one of these duct systems forms the oviducts, uterus, and vagina, and the other remains rudimehtary. If the individual is destined to become a male, the potentially female ducts remain rudimentary and the other set gives rise to the duct system of the testes. In dealing with the embryology of the reproductive organs, therefore, conditions as they exist in the indifferent stage (Fig. 123) form a common starting point for the consideration of the later developmental changes in either sex.

Origin of the Gonads. From their earliest appearance the gonads are intimately associated with the nephric system. While the mesonephros is still the dominant excretory organ, the gonads arise as ridge-like thickenings (gonadial ridges, germinal ridges) on its ventromesial face (Fig. 108, F, and 138). Histologically the gonadial ridge consists essentially of a mesenchymal thickening covered by mesothelium. The mesothelial coat of the developing gonad is directly continuous with the mesothelium covering the mesonephros — is in fact merely a part of it stretched over the mesenchymal thickening. It soon, however, begins to show characteristics which differentiate it from the adjacent mesothelium. It grows markedly thicker and its cells round out and increase in size. Some of the cells in the germinal

212

THE DEVELOPMENT OF IHE UROGENITAL SYSTEM

Fig. 123. Schematic diagram showing plan of urogenital system at an early stage when it is still sexually undifferentiated. (Modified from Hertwig.)

epithelium, as this modified layer of mesothelium is now termed, are conspicuously larger than their neighbors. These large cells are the primordial germ cells of the gonad. Considerable evidence has been adduced of late that these germ cells are not formed in situ by the differentiation of mesothelial cells. It is maintained that they can be identified elsewhere in the body before they appear in the germinal epithelium, and that they migrate from their place of origin (yolk-sac entoderm) to settle down in the germinal epithelium and there rear their families. Whatever their previous history may be, they are

THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 213

clearly recognizable in the germinal epithelium and it is not difficult to follow their differentiation from then on, through succeeding generations, to give rise, finally, to the gametes.

If the gonad is to develop into a testis the cells of the germinal epithelium grow into the underlying mesenchyme and form cord-like masses. These cords eventually become differentiated into the seminiferous tubules in which the spermatozoa are formed. In case the gonad develops into an ovary the primordial germ cells grow into the mesenchyme and there become differentiated into ovarian follicles containing the ova. (See Chap. 2.)

The Sexual Duct System in the Male. The ducts which in the male convey the spermatozoa away from the testis are, with the exception of the urethra, appropriated from the mesonephros — a developmental opportunism facilitated by the proximity of the growing testes to the degenerating mesonephros (Fig. 128). The mesonephric structures which are taken over by the testes are shown schematically in figure 124.

Epididymis. Some of the mesonephric tubules which lie especially close to the testes arc retained as the efferent ductules (Figs. 3 and 124). They, together with that part of the mesonephric duct into which they empty, become the epididymis. Cephalic to the tubules which are converted into efferent ductules a few mesonephric tubules sometimes persist in vestigial form as the appendix of the epididymis. Caudal to the efferent ductules a cluster of mesonephric tubules almost invariably persists in rudimentary form as the paradidymis.

Ductus Deferens, Seminal Vesicle, and Ejaculatory Duct. Caudal to th^ epididymis the mesonephric duct receives a thick investment of smooth muscle and becomes the ductus (vas) deferens. A short distance before the vasa deferentia enter the urethral part of the urogenital sinus, local dilations appear in them which become elaborately sacculated and form the seminal vesicles (Fig. 3). The short part of the mesonephric duct between the seminal vesicles and the urethra constitutes the ejaculatory duct. From this point on, the spermatozoa traverse the urethra which thus serves as a common passageway to the exterior for both the sexual cells and the renal excretion.

Prostate and O^wper’s Glands. From the urethral epithelium the prostate and bulbo-urethral glands develop. The prostate sur* rounds the urethra near the neck of the bladder; the bulbo-urethral (Cowper’s) glands lie adjacent (Fig. 124). Their secretions, discharged

214

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

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c X) o 3 <0 ^

2

Kidney

App.of epid. Epididymis

Paradidymis

'

— Diaphragmatic ligament

• Appendage of testis ( hydatid)

Mullerian duct

Mesonephric duct (Vos deferens)

Scrotum

Inguinal ligament (gubernaculum)

Opening of

/V* if!

ejaculatory duct

(mesonephric d.) —

a :

Testis rr

(after descent)

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N

\ â– 

Openings of ureters

Prostotic sinus

Prostate gland

Bulbo -urethral gland

Urethra (penile)

Fig. 124. Diagram of the male sexual duct system in mammalian embryos. (Modified from Hertwig.)

into the urethra with that of the seminal vesicles, serve as a conveying fluid for the spermatozoa.

The Female Duct System. The Mullerian ducts first appear close beside and parallel to the mesonephric ducts. They are the primordial structures from which the uterine tubes (oviducts), uterus, atid vagina arise in the female. It is possible that phylogenetically the Mullerian ducts arose directly from the mesonephric ducts. Ontogenetically in the mammals any such process of splitting has been slurred over and they seem to arise side by side from the same parent tissue. The mesonephric ducts become well developed earlier than the Mullerian ducts and it is very easy to overlook the Miillerian ducts

THE DEVELOI^MENT OF THE INTERNAL REPRODUCTIVE ORGANS 215

Fig. 125. Diagram of the female sexual duct system in mammalian embryos.

(Modified from Hertwig.)

altogether in young specimens. By the time embryos have reached 30 or 40 mm. in length, however, it should be possible to locate them readily in sections or, with care, by dissection.

Vagina. When the Mullerian ducts first appear they are paired throughout their entire length. At their cloacal ends the right and left ducts lie close to the mid-line. In this region they soon approach and fuse with each other in the mid-line to form the vagina (Fig. 125).

Uterus. In some of the primitive mammals fusion of the Mullerian ducts does not progress cephalad beyond the vagina. Such animals have paired uteri formed by enlargement of the Mullerian ducts cephalic to their entrance into the vagina (Fig. 126, A). In all the higher mammals, fusion of the Mullerian ducts involves the caudal end of the uterus so that it opens into the vagina in the form of an

216

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

Fig. 126. Four types of uteri occurring in different gioups of mammals. (After Wiedersheim.)

A, Duplex, the type found in marsupials.

B, Bipartite, the type found in certain rodents.

C, Bicornate, the type found in most ungulatse, and carnivores.

D, Simplex, the type characteristic of the primates.

unpaired neck or cervix. Toward the ovary from the cervix there is great variation in the degree of fusion encountered in the different groups (Fig. 126, B, C, D). In the sow the fusion is carried only a short way beyond the cervix to form a typical bicornate uterus (Fig. 126, C).

Uterine Tubes. The part of the Mullerian duct between the uterus and the ovary remains slender and forms the uterine tube (oviduct). Near its cephalic end; but not usually at the extreme tip, a more or less funnel-shaped opening develops {ostium tubae abdominale). In different forms the detailed configuration of the ostium and its relation to the ovary are quite variable. Conditions range all the way between a pouch-like dilation which almost completely invests the ovary (sow), and an elaborately fringed, funnel-shaped ostium which opens in the general direction of the ovary (man). Whatever the morphological eccentricities of the ostium may be, they appar

THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 217

ently make less difference in its efficiency in picking up the discharged ovum than one might suppose. Even in forms where the relation of the ostium to the ovary is least intimate, abdominal pregnancies resulting from the fertilization of an ovum which the ostium failed to catch and start on its way to the uterus are comparatively uncommon.

Vestigial Structures in the Genital Duct System. In the conversion of the primordial duct systems to their definitive conditions, some of the parts which are not utilized in the formation of functional structures persist in vestigial form even in the adult. Mention has already been made of the rudimentary mesonephric tubules which persist in the male as the paradidymis and the appendix of the epididymis. Traces of the old Mullerian duct system also can usually be found in the male. Attached to the connective tissue investing the testis there is sometimes a well-marked vesicular structure called the appendix of the testis {hydatid) which represents the cephalic end of the Mullerian duct. These ducts also leave a vestige at their opposite ends in the form of a minute diverticulum {prosiaiic simis^ vagina mascidina) which persists where the fused Mullerian ducts opened into the urogenital sinus (Fig. 124).

In the iemale the ostium of the oviduct does not ordinarily develop at the extreme cephalic end of the Mullerian duct. The tip of the duct is likely to persist in rudimentary form as a stalked vesicle (hydatid) attached to the oviduct (Fig. 125).

The mesonephric tubules and ducts may remain recognizable to a variable extent. Usually there is embedded in the mesovarium a cluster of blind tubules and traces of a duct, corresponding to the part of the mesonephric duct and tubules which in the male form the epididymis. Ifhese vestiges are called the epodphoron. Less frequently the more distal portion of the mesonephric duct (the part which in the male forms the vas deferens) leaves traces known as the canals of Gartner in the broad ligament close to the uterus and vagina.

Changes in Position of the Gonads. Neither the testes nor the ovaries remain located in the body at their place of origin. The excursion of the testes is particularly extensive. Many factors are involved in their descent from the mesonephric region, where they first appear, to their definitive position in the scrotal sac. We can only sketch very briefly the course of events.

The urogenital organs arise in the dorsal body-wall, covered by the mesothelial lining of the coelom. Later when the coelomic mesothelium of the abdominal region is reinforced by connective tissue,

218

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

Diaphragmatic ligament of mesonephros

Mesonephros -Adrenal

Testis Spermatic artery

Aorta Ureter

Umbilical artery

Fig. 127. Dissection showing the relative position of mesonephros, metanephros, and testis in a 33 mm. pig embryo. (Modified from Hill.)

the two layers together constitute the peritoneum. As to position of origin with reference to the body cavity, the urogenital organs may, therefore, be briefly characterized as retroperitoneal. This primary positional relationship is already familiar but it is emphasized again here because it is involved in many phases of the change in position and relations undergone by the reproductive organs.

Descent of the Testes. When the mesonephros begins to grow rapidly in bulk, it bulges out into the coelom, pushing ahead of itself a covering of peritoneum. At either end of the mesonephros the peritoneum is, in this process, thrown into folds. One of them extends cephalad to the diaphragm and is known as the diaphragmatic ligament of the mesonephros 124 and 127). The other, which extends to the

extreme caudal end of the coelom, becomes fibrous and is then known as the inguinal ligament of the mesonephros (Fig. 124). The inguinal ligament is destined to play an important part in the descent of the testes.

We have already seen that when the testis develops it causes a local expansion of the peritoneal covering of the mesonephros to accommodate its increasing mass. As the testis grows, the mesonephros decreases in size and the testis takes to itself more and more of the peritoneal coat of the mesonephros (Figs. 127 and 128). In this

Mesonephric duct,

Renal artery Metanephros

Diaphragm

THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 219

process it becomes closely related to the inguinal ligament of the mesonephros. In effect the inguinal ligament extends its attachment to include the growing testis as well as the shrinking mesonephros. With this change the ligament is spoken of as the gubernaculum (Figs. 124, 129, and 131, A).

In the meantime a pair of coclomic evaginations are formed, one in the inguinal region of each side of the pelvis where the caudal end of the gubernaculum is attached. These are the scrotal pouches. Due perhaps in part to traction exerted by the gubernaculum, the testes and the mesonephric structures which give rise to the epididymis begin to shift their relative position progressively farther caudad (cf. Figs. 127-130). Eventually they come to lie in the scrotal pouches. It would be more direct and vivid to say that the gubernaculum “pulls the testis down.” Although the end results of their association very nearly justify such a phrase, it would not be strictly correct. We would be overlooking the more important factor of differential growth. Failure

Kidney.

Testis, Spermatic artery.

Mesonephros. Mesonephric duct.

Renal artery

•Arteries to mesonephros

.Spermatic artery

.Ureter

Umbilical artery

Fig. 128. Dissection showing the relative size and position of mesonephros, metanephros, and testis in an 87 mm. pig embryo. (Modified from Hill.)

220

THE DEVELOPMENT OE THE UROCiENlTAL SYSTEM

Fig. 129. Dissection of 128 mm. embryo showing an early stage in the descent of the testis. (After Hill.) Abbreviations: A., aorta; B., urinary bladder; E., epididymis (the retrogressing 'mesonephros); G., gubernaculum; K., kidney (metanephros) ; R., rectum; Ring, ‘‘inguinal ring,” the fibrous tissue surrounding the opening (inguinal canal) into the scrotal sac; T., testis; U., ureter; U. A., umbilical artery; W. M., mesonephric (Wolffian) duct and Mullerian duct. The common investment of connective tissue largely conceals the smaller Mullerian duct. In this figure the line of demarcation between the two is most clearly shown just to the left of the gubernaculum.

THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 221

Fig. 130. Dissection of 210 mm. pig embryo showing the testis just entering the inguinal canal. (After Hill.) Abbreviations: A., aorta; B., bladder; E., epididymis; K., kidney; M. D.; Mullerian duct; R., rectum; Ring, inguinal ring; Sp. Art., spermatic artery; T., testis; U. A., umbilical artery; U., left ureter; Ur., right ureter (cut); W. D., mesonephric (Wolffian) duct.

222

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

of the gubernaculum to elongate in proportion to the growth of surrounding pelvic structures is more responsible for the traction exerted on the testis than actual shortening on its part.

In its entire descent, the testis moves caudad beneath the peritoneum. It does not, therefore, enter the lumen of the scrotal pouch directly but slips down under the peritoneal lining and protrudes into the lumen, reflecting a peritoneal layer over itself (Fig. 131). This layer of reflected peritoneum is known anatomically as the visceral tunica vaginalis. In most mammals when the testis has come to rest in the scrotal sac, the canal connecting the sac with the abdominal cavity becomes closed. In some of the rodents, however, it remains patent and the testes descend into the scrotum only during the breeding

Fig. 131. Schematic diagrams illustrating the descent of the testis as seen from the side. Abbreviations: d. def., ductus deferens; Proc. Vag., processus vaginalis (the diverticulum of the peritoneum pushed into the scrotal sac).

season, to be retracted again into the abdominal cavity until the next period of sexual activity. Even in those forms normally exhibiting complete closure of the inguinal canal the obliteration of the opening is not uncommonly incomplete or structurally weak as evidenced by the not infrequent occurrence of inguinal hernias.

Descent of the Ovaries. Although the ovaries move through far less distance than the testes their change in position is quite characteristic and definite. As they increase in size, both the gonads and the Mullerian ducts sag progressively farther into the body cavity. In so doing they pull with them peritoneal folds comparable to the mesenteries of the intestinal tract. As these folds are stretched out they allow the ovaries, uterine tubes, and uterus to move caudally, laterally, and somewhat ventrally (Fig. 125). The peritoneal folds remain attached to the dorsal and lateral body-walls, become reinforced by fibrous tissue, and constitute the broad ligaments. The inguinal liga

THE DEVELOPMENT OF THE INTERNAL REPRODUCTIVE ORGANS 223

ment of the mesonephros which in the male forms the gubemaculum, in the female is caught in the peritoneal folds which form the broad ligaments. When the ovaries move caudad and laterad the inguinal ligament is bent into angular form. Cephalic to the bend it becomes the round ligament of the ovary, caudal to it, the round ligament of the uterus (Fig. 125). Thus the changes in position of the female reproductive organs are carried out in a manner quite different from those in the male. In both sexes the organs arise retroperitoneally, but in the male the testes slide along close to the body-wall beneath the peritoneum, while in the female the ovaries, oviducts, and uterus stretch the peritoneum into a mesentery-like structure which permits a certain latitude of positional change and at the same time serves as a supporting ligament and a path of ingress for blood vessels and nerves.

The Adrenal Glands. The adrenal glands and the accessory chromaffin bodies are endocrine organs which are in no way part of the urogenital system. But the close proximity of the adrenal glands to the kidneys (Figs. 127 and 128) makes it convenient to give them a word of comment at this point.

Certain cells which migrate ventrally from the neural crest at the time the sympathetic ganglia are formed become, not nerve cells, but gland cells active in the production of a specific hormone. Due presumably to the presence of this internal secretion in their cytoplasm they exhibit a characteristic reaction with chromic acid salts which has led to their designation as chromaffin cells. Clusters of these chromaffin cells become located in close proximity to each sympathetic ganglion. These clusters are called the paraganglionic chromaffin bodies. Otheij masses of chromaffin tissue from the same source appear in various places beneath the mesoderm lining the coelom. There is usually a considerable amount of chromaffin tissue present in the region of the abdominal sympathetic plexus. This mass constitutes the aortic chromaffin body (organ of Zuckerkandl). The largest mass of extra-sympathetic chromaffin tissue appears just cephalic to the kidney and becomes converted into the medulla of the adrenal.

The cortical portion of the adrenal gland appears very early in development. Even in embryos of 9~12 mm. there is accelerated local proliferation of cells from the splanchnic mesoderm around the notch on either side of the base of the primary dorsal mesentery adjacent to the cephalic pole of the mesonephros. These cells push into the underlying mesenchyme and begin to show a tendency to become arranged in cords. By the 15-17 mm. stage the aggregation

A 1 . 115mm,

Fig. 132. Photographs (X 5) of the external genitalia of a series of pig embryos. Abbreviations: A, anus; C, clitoris; F, genital fold; GC, glans clitoridis; GP, glans penis; L, labia majora; N, labia minora (nymphae); O, urogenital orifice; P, penis; Pr, prepuce; Proc, proctodaeum; R, raphe; S, genital swelling; Sc, scrotum; T, genital tubercle.

THE EXTERNAL GENITALIA

225

of cell cords which constitutes the primordium of the adrenal cortex is quite conspicuous (Fig. 138). Later in development the migrating cells which give rise to the medulla of the adrenal invade the cortical primordium and become encapsulated within it.

III. The External Genitalia

Indifferent Stages. Still another thread in the story which has to be picked up separately is the development of the external genitals of either sex by divergent differentiation from a common starting point.

In very young embryos there is formed in the mid-line just cephalic to the proctodaeal depression, a vaguely outlined elevation known as the genital eminence. This is soon differentiated into a central prominence {genital tubercle) closely flanked by a pair of folds {genital Jolds) extending toward the proctodaeum. Somewhat farther to either side are rounded elevations known as the genital swellings (Figs. 132, A, B, C). Between the genital folds is a longitudinal depression which attains communication with the urogenital sinus to establish the urogenital orifice (ostium urogenitale). This opening is separated from the anal opening by the urorectal fold (Figs. 118, 122, and 132

A-C).

The Male Genitalia. If the individual develops into a male the genital tubercle becomes greatly elongated to form the penis, the genital folds ensheath the penis as the prepuce, and the genital swellings become enlarged to form the scrotal pouches (Fig. 132, C, D, E, F). During the growth of the penis there develops on its caudal face a groove extending throughout its entire length. Posteriorly the groove is continuous with the slit-like opening of the urogenital sinus. This groove in the penis later becomes closed over by a ventral fusion of its margins, establishing the penile portion of the male urethra. That portion of the urogenital sinus between the neck of the bladder and the original opening of the urogenital sinus becomes the prostatic urethra (Fig. 118, F). Since the margin of the slit-like urogenital orifice closes coincidently with the closure of the urethral groove in the penis, the prostatic urethra and the penile urethra become continuous and the urogenital orifice is projected to the tip of the penis. The line of fusion in the urogenital sinus region and along the caudal surface of the penis is clearly marked by the persistence of a ridge-like thickening known as the raphe (Fig. 132, D, E, F).

Female Genitalia. In the female the genital tubercle becomes the clitoris, the genital folds become the labia minora and the genital

226

THE DEVELOPMENT OF THE UROGENITAL SYSTEM

swellings the labia raajora (Fig. 132, C, G, H, I). The original opening of the urogenital sinus undergoes no such changes ds occur in the male but persists nearly in its original position. Its orifice, enlarged and flanked by the labia, becomes the vestibule into which open the vagina and the urethra (Fig. 118, E). The urethra in the female is derived entirely from the urogenital sinus, being homologous with the prostatic portion of the male urethra.

Chapter 11

Tlie Development of tke Circulatory System

I. The Interpretation of the Embryonic Circulation

The embryonic circulation is difficult to understand only when the meaning of its arrangement is overlooked. If one bears in mind certain fundamental conceptions as to the significance of the circulatory system in organic economics, and the basic morphological principle that any embryo must go through certain ancestral phases of organization before it can arrive at its adult structure, the changes in the arrangement of vascular channels during the course of development form a coherent and logical story.

In the embryo as in the adult the main vascular channels lead to and from the centers of metabolic activity. The circulating blood carries food from the organs concerned with its absorption to parts of the body remote from the source of supplies; oxygen to all the tissues of the body from organs which are especially adapted to facilitate the taking of oxygen into the blood ; and waste materials from the places of their liberation to the organs through which they are eliminated. One of the primary reasons the arrangement of the vessels in an embryonic mammal differs so much from that in the adult, is the fact that the emjbryo lives under conditions totally unlike those which surround its parents. Its centers of metabolic activity are, therefore, different; and, since the course of its main blood vessels is determined by these centers, the vascular plan is different. No such profound changes occur between the embryonic and the adult stages in the circulation of a fish where embryo and adult are both living under similar conditions.

The organs which in the adult mammal carry out such functions as digestion and absorption, respiration, and excretion are extremely complex and highly differentiated structures. They are for this reason slow to attain their definitive condition and are not ready to become functional until toward the close of the embryonic period. Moreover the conditions which surround certain of the developing organs during

227

228

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

intra-uterine life absolutely prevent their becoming functional even were they suflSciently developed so to do. Suppose^ the lungs, for example, were functionally competent at an early stage of development. The fact that the embryo is reliving ancestral conditions in its private amniotic aquarium renders its lungs as incapable of functioning as those of a man under water. Likewise the developing digestive organs of the embryo are inaccessible to raw food materials. Further examples are not necessary to make it obvious that were the embryo dependent on the same organs which carry on metabolism in the adult, development would be at an impasse.

An embryo must, nevertheless, solve the problem of existence during the protracted time in which it is building a set of organs similar to those of its parents. In the absence of a dowry of stored food in the form of yolk, the mammalian embryo draws upon the uterine circulation of the mother. Utilization of this source of supplies depends on the development of a special organ which serves through fetal life and is then discarded. The embryo takes food not into its slowly developing gastro-intestinal tract but into its chorion, a membrane projected outside its own body and applied to the uterine wall to form, together with it, the placenta. The nutritive materials there absorbed from the maternal blood must be transported to the body of the growing embryo by its own blood stream.

The use of food materials to produce the energy expressed in growth depends on the presence of oxygen. For growth there must be a means of securing oxygen and carrying it, as well as food, to all parts of the body. Nor can continued growth go on unless the waste products liberated by the developing tissues are eliminated. The blood of the embryo cannot be relieved of its carbon dioxide and acquire a fresh supply of oxygen in the primordial cell clusters which will later become its lungs. It cannot excrete its nitrogenous waste products through undeveloped kidneys. Its respiration and excretion, like its absorption of food, are carried out in the rich plexus of small blood vessels in the chorion. Here the fetal blood is separated from the maternal, by tissues so thin that it can readily give up its waste materials to, and receive food and oxygen from, the maternal blood stream, just as the mother’s own tissues constantly carry on this interchange with the circulating blood. The placenta is thus the temporary alimentary system, lung, and kidney of the mammalian embryo. The large size of the umbilical blood vessels to the placenta is not a surprising thing — it is the entirely logical, the inevitable, expression of the conditions under which the embryo develops.

THE INTERPRETATION OF THE EMBRYONIC CIRCULATION 229

The enormous chorionic blood supply during fetal life, with the entire disappearance of this special arc of the circulation when the organism assumes adult methods of living, is a striking example of the determination of vascular channels by the location of functional centers. We must not, however, overlook the fact that there are many other centers of activity in the growing embryo less conspicuous but equally important for its continued existence. Each developing organ in the embryonic body is a center of intense metabolic activity. During fetal life it must be supplied by vascular channels adequate to care for its growth. But that is not all. Up to the time of birth each organ has been drawing on blood furnished with food and freed of waste materials by the activities of the maternal organism. At birth all this must change. Each organ essential to metabolism must be ready to assume its own active share in the process. Their vessels must be adequate to take care not only of the needs of these organs themselves but also of the functions these organs must now take over in maintaining the metabolism of the organism as a whole.

While the functional significance of the arrangement of the blood vessels is always of importance, especially in understanding the progressive changes in vascular plan, there is another factor which we cannot overlook. This factor is conservative, having to do with the things we inherit from our forebears. The goal of the embryonic period is the attainment of a bodily structure similar to that of the parents. Because it is so familiar, we accept with complaisance the remarkable fact that this goal is attained with absolute regularity. Accidents there may be, leading to defective development or malformation — but the fertilized ovum of a pig never gives rise to a cow. The new individual will show detailed differences from its parents, differences which are capitalized in the slow march of evolution; but in a single generation these differences are never radical. We say that the offspring has inherited the structure of its parents. It does more. It inherits the tendency to arrive at its adult condition by passing through the same sort of changes which its ancestors underwent in the countless millions of years it took their present structure to evolve.

Applied to the development of the circulatory system of mammals this means that the earliest form in which it appears will not be a miniature of the adult circulation. The simple tubular heart pumping blood out over aortic arches to be distributed over the body and returned to the posterior part of the heart by a bilaterally symmetrical venous system, in short the vascular plan which we see in young

230

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

mammalian embryos (Fig. 45), is essentially the plan of the circulation in fishes. When we realize this, we are not puzzled either by the appearance of a full complement of aortic arches, or by their subsequent disappearance to make way for a new respiratory circulation in the lungs. We see the march of progress from a logical beginning in ancestral conditions toward the consummation of fetal life with an organization like that of the parent.

In addition to the fundamental ground plan of the circulation of the mammalian embryo, recapitulations account for many transitory peculiarities. The formation of a conspicuous though empty yolk-sac with a complement of blood vessels almost as well developed as the vitelline vessels of animals well endowed with yolk, is clearly a recapitulation of ancestral conditions. So also is the highly developed system of venous channels in the mesonephros. If the organ itself appears it brings with it its quota of vessels, no matter whether or not the organ is destined to degenerate later in development.

Whatever peculiarities may be impressed on the course of the circulation by the appearance of ancestral structures or by the development of special fetal organs such as the yolk-sac and the placenta, the main blood currents will at any time be found concentrated at the centers of activity. Changes of these main currents as one center retrogresses and another becomes dominant, must take place gradually. Large vessels become smaller, what was formerly an irregular series of small vessels becomes excavated to form a new main channel, but the circulation of blood to all parts of the body never ceases. Even slight curtailment of the normal blood supply to any region would stop its growth ; any marked local decrease in the circulation would result in local atrophy or malformation ; complete interruption of any important circulatory channel, even for a short time, would inevitably mean the death of the embryo.

II. The Arteries

The Derivatives of the Aortic Arches. In vertebrate embryos six pairs of aortic arches are formed connecting the ventral with the dorsal aorta. The portions of the primitive paired aortae which bend around the anterior part of the pharynx constitute the first (i.e., the most anterior) of these aortic arches. In its course around the pharynx the first aortic arch is embedded in the tissues of the mandibular arch (Fig. 136, A). The other aortic arches develop later, in sequence, one aortic arch in each branchial (gill) arch posterior to the mandibular

232

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

Worsotremnanf,

^ofl^aorftcarch

'd^aorfic arch fyorhc sac S^aorhcarch A^aorhcarch )POhnonaryarch

Right dorsal aorta

\Ana5t0mosiS'

External carotid! artery External carotid artery 5^ aortic arch

4^ aortic arch Pulmonary arch Pulmonary artery

Left dorsal aorta

Putmonary Segmental arteries

Subclauian artery

Aorta

Fig. 134. Ventral aspect of vessels in the branchial region of pig embryos of various ages. (After Heuser.) The drawings in this and the three following figures were made directly from injected specimens rendered transparent by treatment with wintergreen oil. A, 24 somites; B, 4.3 mm.; C, 6 mm.; D, 8 mm.; E, 12 mm.

ftemnant of right pu/mo' nary arch.

Pufmanaryarch â– PuknonatyMfery fbsienor cervical arhny

'^Bmehat artery StMnor mtercos*

SubckMan artery

234

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

arches, leaves only the ventral and dorsal aortic roots and the third, fourth, and sixth arches to play an important r61e in the formation of adult vessels.

In dealing with embryos of 9 to 12 mm. we have already seen how the portions of the ventral aortic roots which formerly acted as feeders to the first two arches were retained as the external carotid arteries. These vessels, in part through the small channels left by the disintegration of the aortic arches with which they were originally associated, and in part through the formation of new branches to subsequently formed structures, nourish the oral and cervical regions (Figs. 67, 133 and 137, A, B).

The internal carotid arteries also, are, familiar as vessels which arise as prolongations of the dorsal aortic roots and extend to the brain (Fig. 67). When the portion of the dorsal aortic root which lies between arch 3 and arch 4 dwindles and drops out, the third arch is left constituting the curved proximal part of the internal carotid artery (Figs. 133, B, C, and 137, A~C). The part of the ventral aortic root which, from the first, has fed the third aortic arch becomes somewhat elongated and persists as the common carotid artery (Figs. 133, 137).

The fourth aortic arch has a different fate on opposite sides of the body. On the left it is greatly enlarged and persists as the arch of the adult aorta (Figs. 133 and 134-137). On the right the fourth arch forms the root of the subclavian artery. The short section of the right ventral aortic root proximal to the fourth arch persists as the innominate (brachiocephalic) artery from which both the right subclavian and the right common carotid artery arise (Fig. 133, C).

The sixth aortic arch changes its original relationships somewhat more than the others. At an early stage of development branches extend from its right and left limbs toward the lungs (Fig. 134, D, E). After these pulmonary vessels have been established^ the right side

^ The details of the formation of the pulmonary arteries differ somewhat in different mammals. In most of the forms which have been carefully studied (man, cat, dog, sheep, cow, opossum) the pulmonary arteries maintain their original paired condition throughout their entire length. In these forms part of the right sixth arch is retained as the proximal portion of the adult right pulmonary artery (Fig, 133). The pig is unusual in having its pulmonary branches fuse with each other proximally, forming a median vessel ventral to the trachea (cf. Figs. 134, E, and 135, A). Distal to this short median trunk the pulmonary vessels retain their original paired condition, each running to the lung on its own side of the body. Proximally the median trunk becomes associated with the left sixth arch and the right sixth arch drops out altogether.

THE ARTERIES

235

of the sixth aortic arch loses communication with the dorsal aortic root and disappears (Fig. 135, A, B). On the left, however, the sixth arch retains its communication with the dorsal aortic root. The portion of it between the point where the pulmonary trunk is given off and the dorsal aorta is called the ductus arteriosus (Figs. 133, C, and 138). During the fetal period when the lungs are not inflated the ductus arteriosus shunts the excess blood from the pulmonary circulation directly into the aorta. The functional importance of this channel will be more fully appreciated when we have given it further consideration in connection with the development of the heart and the changes which take place in the circulation at the time of birth.

While these changes have been taking place in the more peripheral part of the vascular channels which lead to the lungs, a fundamental alteration has occurred in the main ventral aortic stem. Formerly a single channel leading away from the undivided ventricle of the primitive tubular heart, the ventral aorta now becomes divided lengthwise into two separate channels. This division begins in the aortic root just where the sixth arches come off, and progresses thence toward the heart. Meanwhile, as wc shall see when we take up the development of the heart, the ventricle has become divided into right and left chambers. The final result of these two synchronous partitionings is the establishment of a channel leading from the right ventricle to the lungs by way of the sixth aortic arches, and another separate channel leading from the left ventricle to the dorsal aorta by way of the left fourth aortic arch.

The Derivatives of the Intersegmental Branches of the Aorta. In dealing with the structure of 9-12 mm. embryos comment was made on the importance of the small intersegmental branches from the dorsal adrta (Figs. 67 and 136, F). At that time, too, we became familiar with some of the vessels which are derived from these branches. The anterior appendage bud first appears at the level of the seventh cervical intersegmental, and it is this artery which becomes enlarged to form the subclavian. With the enlargement of the left fourth aortic arch to form the main channel leading from the heart to the dorsal aorta, the dorsal aortic root on the right side becomes much reduced (Fig. 135, A-D). Caudal to the level of the subclavian it drops out entirely. It will be recalled that the sixth aortic arch also drops out on this side. This leaves the right subclavian communicating with the dorsal aorta by way of a considerable section of the old dorsal aortic root and the fourth aortic arch. In the adult, both the distal part of

236

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

LeffJVaorhc arch

Lehl^Qorh'carch

Optic vesich

Left 3^ aortic arch

Segmental a rtenes

Left dorsal aorta

Lefr pulmonary arch

Left anterior cardinal i/etrt

Left dorsal aorta

LeftS^aorhc arci

Fig. 136. Lateral aspect of vessels in the branchial region of pig embryos of various ages. (After Heuser.) A, 10 somites; B, 19 somites; C, 26 somites; D, 28 somites; E, 30 somites; F, 36 somites (6 mm.).

this vessel (formed by the intersegmental artery) and its proximal portion (appropriated from the old aortic arch system) pass under the name subclavian. This accounts for the striking dissimilarities of origin between the right and left subclavian arteries in the adult.

THE ARTERIES

237

VtrhbmlarUry

Fig. 137. Continuation of the same series of lateral views of injected embryos. A, 14 mm.; B, 17 mrn.; C, 19.3 mm.; D; 20.7 mm.

Cephalic to the subclavian arteries, a series of longitudinal anastomoses appear connecting the cervical intersegmentals to form the vertebral arteries (Fig. 137). When the vertebral arteries are thus established, all the intersegmental roots back to the subclavian drop out, leaving the vertebral as a branch of the subclavian (Figs. 1 33, C,

238

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

and 137). The manner in which the vertebrals swing in to the mid-line rostrally and become confluent with each other to form the basilar artery, and the anastomosis between the internal carotids and the basilar artery in the region of the hypophysis, are already familiar.

Caudal to the subclavian, the internal mammary artery is formed by longitudinal anastomosing of the more cephalic of the thoracic intersegmental arteries. Subsequent dropping out of the proximal parts of the other intersegmentals leaves it arising from the subclavian. Thus the steps in its origin are strikingly similar to the processes by which the vertebral artery was established cephalic to the subclavian (Fig. 133). Still farther caudally in the body, the intersegmental arteries retain their original independent condition as paired branches extending from the aorta dorsad on either side of the neural tube and the developing spinal column (Fig. 67). Even in the adult these vessels appear with little change in their original relations.

The Enteric Arteries. The first of the three enteric arteries to appear is the anterior {superior) mesenteric. We have already followed its origin as a pair of arteries originally called the omphalomesentcrics which, in young embryos, extended to the surface of the yolk-sac (Fig. 45). When the yolk-sac degenerates and the ventral part of the body closes in, these paired channels fuse with each other to form a median vessel situated in the mesentery and extending to the gut loop in the belly-stalk (Fig. 66). This is now called the anterior mesenteric artery. With the elongation and coiling of the intestine in the region fed by it, the anterior mesenteric artery acquires many radiating terminal branches. Its primary relations, however, remain unchanged.

The celiac artery arises from the aorta in a manner basically similar to the origin of the anterior mesenteric artery, but at a slightly later stage of development. The embryonic body has, therefore, become more nearly closed ventrally and the primary dorsal mesentery has been established. As a result the primary paired condition we expect to see in the early stages of the formation of all of the main enteric arteries is greatly abbreviated in the case of the celiac artery, and almost from its first appearance it is a median vessel extending in the mesentery toward the gastric region of the gut (Fig. 67). As development progresses it becomes extensively branched, being the main artery which feeds the gastro-hepato-pancreatic region of the digestive system and also the spleen which arises in its territory (Fig. 111).

The inferior mesenteric artery has an origin similar to that of the celiac. It is established caudal to the anterior mesenteric artery slightly

THE ARTERIES

239

Choroid plexus of ventricle IZ

Basilar artery

Primordium of occipital bone

Arytenoid process//^; of larynx

Pharyngeal bursa Recurrent laryngeal n

Aortic arch

Ductus arteriosus

Dorsal aorta

Left common cardinal vein

Lung bud

Adrenal gland

Stomach

Pancreas

Gonad

Gut loop in mesentery

Mesonephros

Metanephros

Post cardinal vein

Dorsal root ganglion

Mesocoele

Tuberoulum posterius

Infundib ulum

Rathke's pocket

Foremen of Monro

Tongue Thyroid gland

Pulmonary valves

Pericardial coelom

Septum transversum

Gastric branch of vagus n.

Left umbilical vein in liver

Dorsal

mesogastrium (omental portion)

Gut loop in ^^^^belly-stolk

(umbilical) art

Genital tubercle

Nerves of lumbosocral plexus

Fig. 138. Drawing (X 10) of parasagittal section of 15 mm. pig embryo. The section is in a plane slightly to the left of the mid-line and passes through the ductus arteriosus, lung bud, stomach, gonad, and metanephros.

240

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

later in development than the time at which the celiac appears and is the main vessel to the posterior part of the intestinal tract (Fig. 111).

The Renal Arteries. The mesonephros is suppliea by many small arteries which arise ventro-laterally from the aorta. While the metanephroi or permanent kidneys are still very small, they lie in close proximity to the mesonephroi and are fed by small arteries which arise from the aorta along with the mesonephric vessels (Fig. 127). The local vessels associated with the kidneys are progressively enlarged as the kidneys themselves grow in bulk and become the renal arteries of the adult (Fig. 128).

The Arteries Arising from the Caudal End of the Aorta. The

main aortic trunk decreases abruptly in size where the large umbilical (allantoic) arteries (Fig. 138) turn off into the belly-stalk. Beyond this point the aorta is continued toward the tail as a slender median vessel called the caudal artery (Fig. 67).

The posterior appendage buds arise some time after the placental circulation has been established. The umbilical arteries are consequently of considerable size, and the small vessels which branch off from them to feed the appendage buds are by comparison quite insignificant. As the appendage buds grow, these small vessels grow with them to become the external iliac arteries. When, at birth, the placental circulation stops, the umbilical arteries are reduced to small vessels nourishing the local tissues between their point of origin and the umbilicus. We then know their proximal portions as the internal iliac^ or hypogastric arteries^ and the fibrous cords which still mark their course along the wall of the bladder (the old allantoic stalk) as the obliterated branches of the hypogastric arteries. Thus the tables are turned between fetal and adult life. In the fetus the external iliac artery to the leg appears as a branch of the dominating umbilical artery. After birth the reduced umbilical arteries under their new name of internal iliacs, or hypogastrics, appear as branches of the now larger external iliacs. The original umbilical root proximal to the origin of the external iliac is called the common iliac (Fig. 150).

III. The Veins

There is a natural grouping of the veins according to their relationships which it is convenient to follow in discussing their development. Under the term systemic veins we can include all the vessels which collect the blood distributed to various parts of the body in the routine of local metabolism. In young embryos these would be the cardinal

THE VEINS

241

veins and their tributaries, that is, the return channels of the primitive intra-embryonic circulatory arc. In older embryos and adults the systemic veins would include the anterior (superior) caval system which is evolved from the anterior cardinals, and the posterior (inferior) caval system which takes the place of the postcardinals and their tributaries.

We can set apart from the general systemic circulation three special venous arcs: the umbilical, returning the blood from the })lacenta; the pulmonary, returning the blood from the lungs; and the hepatic portal, carrying blood from the intestinal tract to the liver. I'he specialized nature of the placental and pulmonary circulations is obvious. The peculiarities of the hepatic portal system call, perhaps, for a word of explanation. Ordinarily veins^ collect blood from local capillaries and pass it on directly to the heart. Their blood stream is away from the organ with which they arc associated ; once collected within a vein the blood is not redistributed in capillaries until it has again jiassed through the heart. The portal vein arises in typical fashion by collecting the blood from capillaries in the digestive tube. But then, contrary to the usual procedure, its blood flows, not directly to the heart, but to the liver where it enters a second capillary bed and is returned by a second set of collecting vessels to the heart. With reference to the plexus of capillaries in the liver this vein is aflferent. Hence its designation as a portal (translated = carrying to) vein, setting it apart from other veins which carry blood only away from the organ with which they are associated.

There is a tendency among those who have done but little work on the circulation to regard any vessel which carries oxygenated blood as an artery, and any vessel which carries blood poor in oxygen and high in carbon dioxide content as a vein. This is not entirely correct even for the circulation of adult mammals on which the ( onception is based. In comparative anatomy and especially in embryology it is far from being the .case. It is necessary, therefore, in dealing with the circulation of the embryo, to eradicate this not uncommon misconception.

The differentiation between arteries and veins which holds good for all forms, both embryonic and adult, is based on the structure of their walls, and on the direction of their blood flow with reference to the heart. An artery is a vessel carrying blood away from the heart under a relatively high, fluctuating pressure due to the pumping of the heart. Correlated with the pressure conditions in it, its walls are heavily reinforced by elastic tissue and smooth muscle. A vein is a vessel carrying blood toward the heart under relatively low and constant pressure from the blood welling into it from capillaries. Correlated with the pressure conditions characteristic for it, the walls of a vein have much less elastic and muscle tissue than artery walls, and more non-elastic connective-tissue fibers.

Heart

" Artt Cardinal

Developing SubcordinolPlwu3 in tleson.

SubcL

von

Fig. 139. Diagrams illustrating stages in the development of the systemic veins of the pig. (After Butler.) The cardinal and omphalomesenteric veins are shown in black, the subcardinal system is stippled, the supracardinals are horizontally hatched, and vessels arising independently of these three systems are indicated by small crosses,

A, Ground plan of the veins of a young mammalian embryo (cf. Fig. 45).

B, Cross-section (at level of arrow in A) showing dorso-ventral relations of the various veins.

C, Diagrammatic plot of veins of mm. pig embryos.

D, Arrangement of veins in 6“-7 ram. pig embryos.

242

Juoulor;;,

E, Cross-section (at level of arrow in D) showing dorso- ventral relations of vessels.

F, Veins in 12—13 mm. embryos.

G, Veins in 16-19 mm. embryos.

H, Veins in 22-24 mm. embryos.

I, Veins in 30-35 mm. embryos.

J, Cross-section of 17 mm, embryo at level of arrow in G.

K, Plan of veins in adult pig^

243

244

THE DEVELOPMENT OF THE CTRC.ULATORY SYSTEM

Changes in the Anterior Systemic Veins Resulting in the Establishment of the Anterior (Superior) Vena <^va. The main tributaries draining the anterior parts of the adult body are the external and internal jugulars and the subclavians. In 12 mm. embryos we saw all these vessels laid down. The internal jugular is merely the original anterior cardinal under a new name. The external jugular develops from the small branch draining the mandibular region, and the subclavian as an enlargement of one of the segmental tributaries at the level of the anterior appendage bud (Fig. 68).

When the appendage buds first appear, the heart lies far forward in the body. As development progresses it is carried caudad. With this change in the position of the heart, the common cardinal veins (ducts of Cuvier) change their relative position in the body and come to lie caudal to the anterior appendage buds. As a result of this altered relation the subclavian veins from the anterior appendages, which early in development drain into the posterior cardinals (Fig. 139, C) eventually empty into the anterior cardinals (Fig. 139, G).

The outstanding characteristic of the systemic venous plan of a young embryo is its bilateral symmetry. Paired vessels from the anterior and from the posterior parts of the body become confluent to enter the sinus region of a simple tubular heart (Figs. 1 39, A and 144, A-C). The rerouting of the blood to enter the right side of the heart is the all-important end toward which the mammalian venous system is progressing throughout its development. In dealing with local changes this basic trend should never for a moment be forgotten.

In the anterior systemic channels this shift to the right is accomplished very simply and directly. A new vessel forms between the right and left anterior cardinals and shunts the left anterior cardinal blood stream across to the right (Fig. 139, H). With the establishment of this new channel, the part of the left anterior cardinal toward the heart drops out (Fig. 139, I). We have now but to apply the familiar adult names (Fig. 139, K): the new connecting vessel is the left innominate; the old anterior cardinal between the union of the subclavian with the jugulars and the new transverse connection is the right innominate ; from the confluence of the innominates to the heart is the anterior vena cava. The anterior vena cava is thus composed of the most proximal part of the right anterior cardinal and the right common cardinal vein (duct of Cuvier). The small azygos (cervicothoracic) vein, which is the reduced posterior cardinal, indicates the old point of transition from anterior cardinal to common cardinal.

THE VEINS

245

Changes in the Posterior Systemic Veins Resulting in the Establishment of the Posterior (Inferior) Vena Cava. The changes in the systemic veins of the posterior part of the body are much more radical than they are anteriorly. The posterior cardinal veins which are the primitive systemic drainage channels are associated primarily with the mesonephroi. When the mesonephroi degenerate, it is but natural that the posterior cardinals should degenerate with them. Hie posterior vena cava which replaces the cardinals is a composite vessel which gradually takes shape by the enlargement and straightening of small local channels which are, as it were, pressed into service as the posterior cardinals degenerate.

The subcardinal veins initiate the diversion of the postcardinal blood stream. The subcardinals arc established as vessels lying along the ventro-mesial border of the mesonephros parallel with, and ventral to, the postcardinals. Taking origin from an irregular plexus of small vessels emptying from the mesonephroi into the posterior cardinals, the subcardinals from their first appearance have many channels connecting them with the postcardinals (Fig. 139, A-C). As the mesonephroi increase in size and bulge toward the mid -line the subcardinals are brought very close together. In the mid -mesonephric region they anastomose with each other to form a large median vessel, the subcardinal sinus, or intersubcardinal anastomosis (Figs. 60, 77, and 139, D-F). When this sinus is established the small vessels connecting sub- and postcardinals drain into the capacious sinus rather than toward the posterior cardinals. The result of this change very soon becomes apparent in the disappearance of the posterior cardinals at the level of this sinus. The blood from the posterior part of the body is still collcctecl by the distal ends of the postcardinals but it returns to the heart by way of the subcardinal sinus. Consequently the anterior portions of the posterior cardinals, although they persist, are much reduced in size (Fig. 139, F).

Meanwhile the increased volume of blood entering the subcardinal sinus is finding a new and more direct route to the heart. The cephalic pole of the right mesonephros lies close to the liver. A fold of dorsal body-wall tissue, just to the right of the primary dorsal mesentery, early makes a sort of bridge between these two organs. This fold is known as the caval plica {caval mesentery) (Fig. 140). In it, as everywhere in the growing body, are numerous small vessels. Connection of these small vessels with the plexus of channels in the liver cephalically (Fig. 140, A), and the mesonephros caudaliy (Fig. 140, B),

246

THE DEVELOPMENT OF THE CIRCULATORY SYSl’EM

' : Dorsal aorta

Posterior cardinal vein^rV

Cava leaving ‘ : mesonephros^

Caval plica hCava

entering liver

Stomach

Ductus venosus

Gall-bladder

Rt umbilical vein

Fig. 140. Drawings of transverse sections of 5 mm. pig embryos showing the relations of the caval fold of the mesentery (caval plica). A, Section at level where cephalic end of caval plica merges with liver. Here the small vessel which is the primordium of the mesenteric portion of the posterior vena cava enters the sinusoidal circulation of the liver. B, Section showing merging of caudal end of caval plica with right mesonephros. At this level the developing mesenteric portion of the posterior vena cava anastomoses with the right subcardinal vein (cf. Fig. 139, D).

provides the entering wedge. Once a current of blood finds its way from the mesonephros to the liver through these small vessels, enlargement of the channel proceeds with great rapidity. This new channel becomes the mesenteric part of the inferior vena cava, (See relations of posterior vena cava in figures 75 and 76, and portion of cava indicated with small crosses in figure 139, D.)

Within the liver this new blood stream at first finds its way by devious small channels eventually entering the sinus venosus along with the omphalomesenteric circulation. As its volume of blood increases it excavates through the liver a main channel which gradually becomes walled in. As this new vessel becomes more and more definitely organized it gradually crowds toward the surface and eventually appears as a great vein lying in a notch along the dorsal side of the liver. This is the hepatic part of the inferior vena cava.

From the subcardinal sinus the most direct route to this new

THE VEINS

247

outlet is by way of the right subcardinal vein. Thus in embryos as young as 9 to 12 mm., the formation of the posterior vena cava is well started with its proximal portion consisting of subcardinal sinus, a portion of the right subcardinal vein, and the new channels through the mesentery and through the liver. (Follow this part of the cava through figure 139 from D to K.)

Posterior to the level of the subcardinal sinus still amother set of veins enters into the formation of the post-cava. These are the supracardinal veins which appear, relatively late in development, as paired channels draining the dorsal body-wall (Fig. 139, G, J).

At the mid-mesonephric level, the supracardinals are diverted into the subcardinal sinus just as happened with the postcardinals earlier in development. Cephalic to the sinus, parts of the supracardinals persist as the azygos group draining in a somewhat variable manner into the reduced proximal part of the postcardinals. Caudal to the anastomosis with the subcardinal sinus, the right supracardinal becomes the principal drainage channel of the region. Its appropriation of the tributary vessels from the posterior appendages establishes it as the postrenal portion of the inferior vena cava and is the last step in the formation of that composite vessel (Fig. 139, G—K).

The Coronary Sinus. The ultimate fate of the left common cardinal vein (duct of Cuvier) is a result of the shift in the course of the systemic blood so that it all enters the right side of the heart. Formerly returning a full half of the systemic blood stream to the heart, the left common cardinal vein is finally left almost without a tributary from the body. In the pig a small amount of blood usually does continue to enter it over the left azygos (Fig. 139, K). Occasionally in the pig, and normally in most other mammals, even this is cut off and the azygos drainage is by way of the right side to the superior cava (dotted line in Fig. 139, K). Nevertheless the proximal part of the old left cardinal channel is utilized. Pulled around the heart in the course of the migration of the sinus venosus toward the right, the left common cardinal vein lies close against the heart wall for a considerable distance (Fig. 144, D). As the heart muscle grows in bulk it demands a greater blood supply for its metabolism. The small returning veins of this circulation find their way into this conveniently located main vessel (Fig. 144, E). Thus even when its peripheral circulation is cut off the left common cardinal vein still persists as the coronary sinus into which the vessels of the cardiac wall drain (Fig. 144, F).

248

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

right

omplLv'

right

iimb.v,

umb. vein* fused in belly stalk

coronary sinus (left duct of

hepatic v, (omph.)

left

umb.v« 

Fig. 141. Diagrams showing the development of the hepatic portal circulation from the omphalomesenteric veins, and the relations of the umbilical veins to the liver. (Adapted from several sources.)

A is based on conditions in pig embryos of 3-4 mm.; B, on embryos of about 6 mm.; C, on embryos of 8-9 mm.; D, on embryos of 20 mm. and older.

THE VEINS

249

The Pulmonary V eins. Phylogenetically the lungs are relatively new structures. It is not surprising, therefore, that we find the pulmonary veins arising independently and not by the conversion of old vascular channels. They originate as vessels which drain the various branches of the lung buds and converge into a common trunk (Fig. 107), entering the left atrium dorsally. In the growth of the heart this trunk vessel is gradually absorbed into the atrial wall and two or more of its original branches open directly into the left atrium as the main pulmonary veins of the adult (Fig. 144, D-F).

The Portal Vein. The blood supply to the intestines is first established through the omphalomesenteric arteries which later become modified to form the anterior mesenteric artery. Likewise the drainage of the intestinal tract is provided for by vessels which were originally the return channels of the primitive omphalomesenteric circulatory arc (Fig. 45). In dealing with 9 to 12 mm. embryos we have already seen the primary changes which occur in these vessels. The growing cords of hepatic tissue break up the proximal portion of the omphalomesenteric veins into a maze of small channels ramifying through the substance of the liver (Fig. 141, A, B). But the stubs of the omphalomesenterics persist and drain this plexus. Distal to the liver, the original veins are for a time retained, bringing blood from the yolk-sac and intestines to the liver. With the disappearance of the yolk-sac and the growth of the intestines, the omphalic (yolk-sac) portions of these veins necessarily disappear, but the mesenteric branches persist and become more extensive concomitantly with the increased length and complexity of the intestinal tract.

The original omphalomesenteric trunks into which these tributaries converge become the unpaired portal vein by forming transverse anastomoses and then abandoning one of the original channels. The curious spiral course of the portal vein is due to the dropping out of the original left channel cephalic to the middle anastomosis and the original right channel caudal to the anastomosis (Fig. 141, D).

The Umbilical Veins. When they are first established the umbilical (allantoic) veins are embedded in the lateral body-walls throughout their course from the belly-stalk to the sinus venosus (Fig. 45). As the liver grows in bulk, it fuses with the lateral body-wall. Where this fusion occurs vessels develop connecting the umbilical veins with the plexus of vessels in the liver (Fig. 141, B). Once these connections are established the umbilical stream tends more and more

250

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

to pass by way of them to the liver, and the old channels to the sinus venosus gradually degenerate (Fig. 141, C). ^

Meanwhile the umbilical veins distal to their entrance into the body become fused with each other so that there comes to be but a single vein in the umbilical cord (Fig. 141, C). Following this fusion in the cord, the intra-embryonic part of the umbilical channel also loses its original paired condition. The right umbilical vein is abandoned as a route to the liver and all the placental blood is returned over the left umbilical vein. It is interesting to note that in spite of its ceasing to be a through channel, part of the right umbilical vein persists, draining the body-wall. The small blood stream it then carries is reversed in direction, flowing back into the left umbilical (Fig. 141, D).

When first diverted into the liver, the umbilical blood stream passes through by way of a mesh work of small anastomosing sinusoids. As its volume increases it excavates a main channel through the substance of the liver which is known as the ductus venosus (Figs. 138 and 141, B~D). Leaving the liver, the ductus venosus becomes confluent with the hepatic veins (omphalomesenteric stubs) which drain the maze of small sinusoids in the liver. At this point, also, the vena cava joins the others. Thus the blood streams from the posterior systemic circulation, from the portal circulation, and from the placental circulation all enter the heart together. Embryologically this great trunk vessel represents the fused proximal parts of the old omphalomesenteric veins enlarged by the placental blood from the ductus venosus and by the systemic blood from the vena cava (Fig. 141). During its early developmental phases it is often called the common revehent hepatic vein. In the adult or in older fetuses it is more convenient to regard it as a part of the vena cava because, with the cessation of the placental circulation at the time of birth, the caval blood stream becomes the dominant one.

IV. The Lymphatic System

Important and interesting as the subject is, it has seemed expedient to omit any account of the development of the lymphatic vessels. Those interested in this field will find that an unusual amount of careful work has been done on the development of the lymphatics in pig embryos. References to some of the more important recent papers have been included in the bibliography appended at the end of the book.

BLOOD CORPUSCLES

251

V. Blood Corpuscles

The first blood corpuscles which appear in the circulation are produced extra-embryonically in the blood islands of the yolk-sac (Fig. 48). Later in development there are many blood-forming centers within the embryo. Concerning the establishment of these centers we find the same controversy that was commented on in connection with the origin of blood vessels. It is maintained by some authorities that these centers always arise from cells originally produced in the yolksac blood islands. According to this interpretation some of these blood cells are believed to remain sufficiently undifferentiated to retain their power of active proliferation. As such cells are carried by the circulation to various parts of the body they settle in favorable locations and raise new families of blood corpuscles.

According to the local origin idea it is not necessary to account for all the centers of blood corpuscle formation on the basis of bloodmother-cells wandering in from the yolk-sac and settling down in new locations within the embryo. It is maintained that mesodermal cells arising in the body have the same capacity of becoming differentiated into blood-mother-cells as mesodermal cells which arise in the yolksac. On this interpretation blood-forming centers arise in various parts of the body from blood-mother-cells differentiated in situ from local mesoderm. The recent experimental work tends to indicate that such “local origin” does occur. That this same evidence proves that the origin of blood-forming centers from migrating cells never occurs is by no means so clear.

Whatever the source of the original blood-mother-cells may be we always find them establishing their centers of proliferation in places where the current of the circulation is sluggish. In very young embryos the centers of corpuscle formation are located in the maze of small channels in the yolk-sac and the allantois. When the yolk-sac degenerates and the allantois becomes highly specialized as part of the chorion, these centers cease to be active and new ones are established in connection with such rich vascular plexuses as those in the mesonephros and the liver. Still later other centers appear in the lymphoid organs, and last of all in the bone marrow (Fig. 152).

The histological details of the processes involved in the production of red blood corpuscles and the various types of white blood corpuscles are exceedingly complex. Moreover there is by no means agreement as to the exact manner in which these processes occur, nor as to the

252

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

genetic relations of one type of blood corpuscle to another. This whole subject, other than the recognition of the multiplicity of blood-forming centers and their shifting locations in the embryo at various phases of development, is a special field of histogenesis entirely beyond the scope of an elementary text.

VI. The Heart

To appreciate the significance of the changes which occur in the growing heart one must have in mind the exigencies under which it develops. Starting as a simple tube with the blood passing through

Fig. 142. Ventral aspect of the heart of the pig at various stages showing the formation of the cardiac loop and the establishment of the primary regional divisions of the heart. Drawn (A-E, X 30; F, X 20) from reconstructions made from series in the Carnegie Collection (A-D) and in the Western Reserve University Collection (E, F).

A, 7 somites; B, 13 somites; C, 17 somites; D, 25 somites; E, 3.7 mm. (after flexion); F, 6 mm.

Abbreviations: At., atrium (t., right; 1., left); Bui., aortic bulb (bulbus arteriosus); Endc., endocardial tubes; Myc., cut edge of epi-myocardium; S.V., sinus venosus; Tr. Art., truncus arteriosus; V. ao. r., ventral aortic roots; Vent., ventricle (r., right; 1., left); V.O.M., omphalomesenteric veins.

THE HEART

253

it in an undivided stream, it must become converted into an elaborately valved, four-chambered organ, partitioned in the mid-line and pumping from its right side a pulmonary stream which is returned to the left side and pumped out again as the systemic blood stream. And the heart cannot cease work for alteration ; there can be no interruption in the current of blood it pumps to the growing embryo. This is but one phase of the matter. At the end of gestation the vascular mechanism must be prepared to function under conditions radically different from those surrounding the embryo. In spite of the impossibility of the developing lungs being effectively exercised under air-breathing conditions, they themselves, their blood vessels,

Fig. 143. Sinistral aspect of reconstructions of the pig heart.

A, 13 somite embryo (cf. Fig. 142, B); B, 17 somite embryo (cf. Fig. 142, C); C, 25 somite embryo (cf. Fig. 142, D); D, 3.7 mm. embryo (cf. Fig. 142, E); E, 6 mm. embryo (cf. Fig. 142, F).

Abbreviations: A.C.V., anterior cardinal veins; Al.V., allantoic (umbilical) vein; Ao., aorta; At., atrium; Bui., aortic bulb; Cav. P., posterior vena cava; Cuv. d., duct of Cuvier (common cardinal vein); Myc., cut edge of epi-myocardium; P.C.V.; posterior cardinal vein; S.V., sinus venosus; Sin-at., sino-atrial region of heart; Tr. Art., truncus arteriosus; V. ao. r., ventral aortic roots; Vent., ventricle; V.O.M., omphalomesenteric veins.

254

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

and the right ventricle which pumps blood to them, must at the moment of birth be ready to take over the entire r^esponsibility of oxygenating the blood. And the systemic part of the circulation as well as the pulmonary must be prepared. Throughout intra-uterine development the left side of the heart receives less blood from the pulmonary veins than the right side of the heart receives from the venae cavae. Yet after birth the left ventricle is destined to carry a greater load than the right ventricle. It must pump through the myriad peripheral vessels of the systemic circulation,, sufficient blood to care for the active metabolism and continued growth of the entire body. These are some of the situations which must be faced before the heart can arrive at its adult condition. The manner in which they are met is doubly interesting because they seem at first sight so difficult.

The Formation of the Cardiac Loop and the Establishment of the Regional Division of the Heart. In dealing with the establishment of the circulatory system in very young embryos we saw how the tubular heart was formed by the fusion of paired primordia (see Chap. 5 and especially Figs. 43 and 44). The primary factor which brings about its regional differentiation is the rapid elongation of this primitive cardiac tube. The heart increases in length so much faster than the chamber in which it lies that it is first bent to the right and then twisted into a loop. Since the anterior end of the heart is anchored in the body by the aortic roots, and the posterior end by the great veins, it is the mid-portion of the heart-tube which, in this process, undergoes the most extensive changes in position. This is facilitated by the early disappearance of the dorsal mesocardium which leaves the heart entirely free in its mid-region.

During the period in which the cardiac loop is being formed, the primary regional divisions of the heart become clearly differentiated. The sinus venosus is the thin-walled chamber in which the great veins become confluent to enter the heart at its primary posterior end (Fig. 144). The atrial region is established by transverse dilation of the heart-tube just cephalic to the sinus venosus (Fig. 144).

The ventricle is formed by the bent mid-portion of the original cardiac tube. As this ventricular loop becomes progressively more extensive, it at first projects ventrally beneath the attached aortic and sinus ends of the heart (Fig. 143, A-C). Later it is bent caudally so that the ventricle, formerly situated cephalic to the atrium, is brought into its characteristic adult position caudal to the atrium (Fig. 143, D, E). Between the atrium and ventricle the heart remains

Pulmonary A from Arch 11

Left

Com

CardV

Auricular /

App

Left Superior Pulmonary V

Uft Inf Pul.V

Oblique Vein Hrshall) â–  of L Atrium

Great Cardiac V.

Coronary Sinus ^

toralTOv)

Leff Ventricle

f^XCom Card V Vena Cava)

-Pul Artery

Rt Pul Veins

Right Ventricle

Superior Vena Cava

Sulcus Terminalis

Sinus Venarum

Small Cardiac V

Inferior Vena Cava

Middle Cardiac Vein

Fig. 144. Six stages in the development of the heart, drawn in dorsal aspect to show the changing relations of the sinus venosus and great veins entering heart. (Patten: ‘‘Human Embryology,” The Blakiston Company.)

255

256

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

relatively undilated. This narrow connecting portion is the atrioventricular canal.

The most cephalic part of the cardiac tube undergoes least change in appearance, persisting as the truncus arteriosus connecting the ventricle with the ventral aortic roots (Fig. 142). In very young embryos there is a conspicuous bulge where the truncus arteriosus swings toward the mid-line to break up in the aortic arches. This sharply bent and somewhat dilated region is called the aortic bulb (Fig. 142, B, C). Its location is of interest as being the place at which the paired endocardial primordia first fused with each other (Figs. 43 and 44) and the place at which, later in development, the division of the truncus arteriosus into separate aortic and pulmonary roots will first become apparent. The bulge itself soon merges into the rest of the truncus arteriosus without giving rise to any special structure.

Almost from their earliest appearance the atrium and the ventricle show external indications of the impending division of the heart into right and left sides. A distinct median furrow appears at the apex of the ventricular loop (Figs. 142, E, F, and 144, U, E). The atrium meanwhile has undergone rapid dilation and bulges out on either side of the mid-line (Fig. 144). Its bilobed configuration is emphasized by the manner in which the truncus arteriosus compresses it mid-ventrally (Fig. 142, E, F).

The Partitioning of the Heart. These superficial features suggest the more important changes going on internally. As the wall of the ventricle increases in thickness it develops on its internal face a meshwork of interlacing muscular bands, the trabeculae carneae. Opposite the external furrow in the ventricle these muscular bands become consolidated as a partition which appears to grow from the apex of the ventricle toward the atrium. This is the interventricular septum (Fig. 147).

Meanwhile two conspicuous masses of peculiar, loosely organized mesenchyme (called endocardial-cushion tissue) develop in the walls of the narrowed portion of the heart between the atrium and the ventricle. One of these so-called endocardial cushions of the atrio-ventricular canal is formed in its dorsal wall (Fig. 147, A) and the other is formed opposite, on the ventral wall. These two masses nearly occlude the central part of the canal and thus initiate its separation into right and left channels.

At the same time a median partition appears in the cephalic wall of the atrium. Because another closely related partition is destined

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257

to form here later, this one is called the first interatrial septum or septum primum. In shape it is crescentic with its concavity directed toward the ventricle and the apices of the crescent extending, one along the dorsal wall, and one along the ventral wall of the atrium, all the way to the atrio-ventricular canal where they merge, respectively, with the dorsal and ventral endocardial cushions (Fig. 147). This leaves the atria separated from each other except for an opening called the interatrial foramen primum.

While these changes have been occurring, the sinus venosus has been shifted out of the mid-line so that it opens into the atrium to the right of the interatrial septum (Fig. 147). The heart is now in a critical stage of development. Its simple tubular form has been altered so that the four chambers characteristic of the adult heart are clearly recognizable. Partitioning of the heart into right and left sides is well under way. But there is as yet no division of the blood stream because there are still open communications from the right to

Carotid arch (III) Aortic arch (IV) Pulmonary arch (VI)

Left atrium— Anterior cardinal

Posterior cardinal vein / Interatrial foramen Iv

Septum 1 1

Truncus arteriosus

Pulmonary channel

-Aortic channel

interventricular

foramen

Interventricular

septum

Trabeculae

Valvulae venosae

/ Inferior vena cava

Atrio-ventricular valve

Fio. 145. Reconstruction of the heart of a 9.4 mm. pig embryo cut open somewhat to the right of the mid-line to show its internal structure (cf. Fig. 146).

258

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

the left side in both atrium and ventricle. A little further progress in the growth of the partitions, however, and the two si^cs of the heart would be completely separated. Were this to occur now, the left side

Fig. 146. Section (X 45) through the heart of a 9.4 mm. pig embryo, at the level of the atrio-ventricular canals. (From the series used in making the reconstruction appearing as figure 145. This section may be oriented as passing horizontally through Fig. 145 at the level of the most caudal portion of the interventricular foramen.)

of the heart would become almost literally dry. For the sinus venosus, into which systemic, portal, and placental currents all enter, opens on the right of the interatrial septum, and not until much later do the lungs, and their vessels develop sufficiently to return any considerable volume of blood to the left atrium. The partitions in the

THE HEART

259

ventricle and in the atrio-ventricular canal do progress rapidly to completion (Figs. 147, 148, and 149), but an interesting series of events takes place at the interatrial partition which assures an adequate supply of blood reaching the left atrium and thence the left ventricle.

Just when it appears that the septum primum is going to fuse with the endocardial cushions of the atrio-ventricular canals, closing the interatrial foramen primum and isolating the left atrium, a new opening is established. The more cephalic part of the septum primum ruptures to form the interatrial for amen secundum, thus keeping a route open from the right to the left atrium (Fig. 148).

At about this time the second interatrial partition makes its appearance just to the right of the first. Also crescentic in form, this septum secundum extends its apices along the dorsal and ventral walls of the atrium to fuse with the septum primum near the endocardial cushion mass which now completely divides the atrio-ventricular

Fig. 147. Drawings showing the initial steps in the partitioning of the heart.

A, Slightly schematized drawing from reconstruction of heart of 3.7 mm. pig embryo. The heart has been opened by a diagonally frontal cut in the plane which can be indicated by drawing a line through the labels At. and Vent, in figure 143, D. The dorsal portion of the heart is shown viewed from the ventral side.

B, Slightly schematized drawing from a reconstruction of the heart of a 6 mm. pig embryo. The heart has been opened in a plane which can be indicated by drawing a line through the labels At, and Vent, in figure 143, E. The dorsal portion of the heart is shown viewed from the ventral side.

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THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

septum II

septum I

septum

spurium"

trabeculae

cameae

^ interatrial

foramen II

septum I

interatrial â– " foramen I ^almost closed}

a V canal endocardial cushion

— intervent septum

Fig, 148. Slightly schematized drawing from a reconstruction of the heart of a 9.4 mm. pig embryo. Dorsal part of heart, interior view. The plane in which the heart is opened can be indicated by drawing a line through the center of the interatrial and the interventricular foramina in figure 145.

canals. But the septum secundum never becomes a complete partition. An oval opening of considerable size persists in its center. This is the foramen ovale (Fig. 149).

The newly established septum secundum and the flap-like remains of the septum primum constitute an efficient valvular mechanism between the two atria. When the atria are filling, some of the blood discharged from the venae cavae into the right atrium can pass freely through the foramen ovale by merely pushing aside the flap of the septum primum. The inferior caval entrance lies adjacent to, and is directed straight into, the orifice of the foramen ovale (Fig. 149). Consequently it is primarily — some think exclusively — blood from the inferior vena cava which passes through the foramen ovale into the left atrium. When the atria start to contract, pressure of the blood within the left atrium forces the flap of the septum primum against the foramen ovale, effectively closing it against return flow into the right atrium. Without some such mechanism affording a supply of blood

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261

septum 11

^ interatrial foramen 11

septum I

anterior vena cava

- pulmonary veins

left atrium

coronary

right

ventricle

papillary muscle interventricular

septum

Fig. 149. Schematic drawing based on dissected heart of pig fetus shortly before birth. Interior aspect of dorsal part of heart to show valvular mechanism at foramen ovale.

to its left side, the developing heart could not be partitioned in the mid-line ready to assume its adult function of pumping two separate blood streams.^

While alf these changes have been going on in the main part of the heart, the truncus arteriosus has been divided into two separate channels. Reference has already been made to the start of this process in the aortic root between the fourth and sixth arches (Fig. 133). Continuing toward the ventricle, the division is effected by the formation of longitudinal ridges of plastic young connective tissue of the same type as that making up the endocardial cushions of the atrioventricular canal. These ridges, called truncus ridges^ bulge progres

^ There are on record a few cases of a peculiar cardiac malformation in which this valvular communication was prematurely closed and the left atrium thereby shut off from the right. In all these cases the left side of the heart has not been sufficiently developed to support life for any length of time after birth.

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THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

sively farther into the lumen of the truncus arteriosus and finally meet to separate it into aortic and pulmonary channels. ^ (Note shape of lumen in Figs. 142, F, and 145.) The semilunar valves of the aorta, and of the main pulmonary trunk (Fig. 138), develop as local specializations of these truncus ridges. Toward the ventricles from the site of formation of the semilunar valves the same ridges are continued into the conus of the ventricles. The fact that proximal to the valves these ridges are, for descriptive purposes, called conus ridges should not be allowed to obscure their developmental and functional continuity with the truncus ridges. The truncus and conus ridges follow a spiral course such that where the conus ridges extend down into the ventricles they meet and become continuous with the interventricular septum. The right ventricle then leads into the pulmonary channel and the left into the aorta. With this condition established the heart is completely divided into right and left sides except for the interatrial valve which must remain open throughout fetal life, until, after birth, the lungs attain their full functional capacity and the full volume of the pulmonary stream passes through them to be returned to the left atrium.

This leaves but one of the exigencies of heart development still to be accounted for. If, during early fetal life, before the lungs were well developed, the pulmonary channel were the only exit from the right side of the heart, the right ventricle would have an outlet inadequate to develop its pumping power. For it is only late in fetal life that the lungs and their vessels develop to a degree which prepares them for assuming their postnatal activity, and the power of the heart muscle must be built up gradually by continued functional activity. This situation is met by the ductus arteriosus leading from the pulmonary trunk to the aorta (Fig. 138). The right ventricle is not unprepared for its adult function because it pumps its full share of the blood throughout fetal life. Instead of all going to the lungs, however, part of the blood pumped by the right ventricle passes by way of the ductus arteriosus into the aorta (Fig. 150). As the lungs increase in size, relatively more blood goes to them and relatively less goes through the ductus arteriosus. By the time of birth enough blood is passing through the lungs to support life, and within a short time after birth, under the stimulus of functional activity, the lungs are able to take all the blood from the right side of the heart and the ductus arteriosus is gradually obliterated. The ductus arteriosus, therefore, serves during intra-uterine life as what might be called a ‘‘compensated exercising channel” for the right ventricle.

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263

Changes in the Sinus Region. In following the story of the development of the heart from the functional standpoint, many things of less striking significance have been passed over. Some of these should have a word of comment. Cephalic to the sinus orifice the valvulae venosae which guard it against return flow fuse and are prolonged onto the dorsal wall of the atrium in the form of a ridge called the septum spurium (false septum). This septum is, for a time, too conspicuous to ignore, but it is of little importance in the partitioning of the heart and soon undergoes retrogression.

As the heart grows it absorbs the sinus venosus into its walls so that eventually the anterior and posterior venae cavae and the coronary sinus all open separately into the right atrium (cf. Figs. 147, 148, and 149). Portions of the right valvula venosa are retained as the valves of the caval and coronary orifices. In the adult heart a small external sulcus can usually be found between the entrance of the anterior and the posterior vena cava which records the old line of demarcation between sinus venosus and atrium.

The Atrio-ventricular Valves and the Papillary Muscles. At the point where the atrio-ventricular canals open into the ventricles there are early indications of the establishment of valves. From the partition in the atrio-ventricular canal and from the outer walls on either side, masses of tissue in the shape of thick, blunt flaps project toward the ventricle (Figs. 146 and 148). It is these masses of a primitive type of connective tissue, similar to that in the endocardial cushions of the canal, which later become differentiated into the flaps of the adult valves (Fig. 149). The papillary muscles and tendinous cords which, in the adult, act as stays to these valves, arise by modification of soine of the related trabeculae carneae (cf. Figs. 146, 148, and 149).

The Aortic and Pulmonary Valves. The valves which guard the orifices of the aorta and of the pulmonary artery arise from mesenchymal pads (Fig. 138) already mentioned as developing in connection with the truncus septum. In early histological appearance and in the manner in which this loose tissue gradually becomes organized into the exceedingly dense fibrous tissue characteristic of adult valves, they are similar to the atrio-ventricular valves. They do not, however, develop any supporting strands comparable to the papillary muscles and tendinous cords.

Course and Balance of Blood Flow in the Fetal Heart. All the steps in the partitioning of the embryonic heart lead gradually toward the final adult condition in which the heart is completely divided into

264

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

right and left sides. Yet from the nature of its living conditions it is not possible for the tetus in utero fully to attain the adult type of circulation. The plan of the completely divided circulation is predicated on lung breathing. In the adult the right side of the heart receives the blood returning from a circuit of the body and pumps it to the lungs where it is relieved of carbon dioxide and acquires a fresh supply of oxygen. The left side of the heart receives the blood that has just passed through the lungs and pumps it again through ramifying channels to all the tissues of the body. In the fetus the function of respiration is carried out in the placenta by interchange with the maternal blood circulating through the uterus. The lungs, although in the last part of fetal life they are fully formed and ready to function, cannot actually begin their work until after birth. The radical change which must inevitably take place immediately following birth in the manner in which the blood is oxygenated has led to a widespread belief that there must be revolutionary changes in the routing of blood through the heart and great vessels. However, as the embryology of the circulatory system has been studied more closely from a functional angle it is becoming increasingly clear that the heart and the major vascular channels develop in such a manner that the pumping load on the different parts of the heart remains balanced at all times during fetal life. Moreover, the very mechanisms which maintain this cardiac balance during intra-uterine life are perfectly adapted to rebalance the circulatory load on the new postnatal basis without involving any sudden overloading of previously inactive parts of the vascular system.

To understand the changes in circulation which are so smoothly accomplished at the time of birth it is necessary to have clearly in mind the manner in which the way for them has been prepared during intra-uterine life. In the foregoing account of the development of the interatrial septal complex, emphasis was laid upon the fact that at no time were the atria completely separated from each other. This permits the left atrium, throughout prenatal life, to receive a contribution of blood from the inferior cava and the right atrium by a transseptal flow which compensates for the relatively small amount of blood entering the left atrium of the young embryo by way of the pulmonary circuit, and maintains an approximate balance of intake into the right and left sides of the heart.

The precise manner in which this transseptal flow occurs, and where, and to what extent the various blood streams of the fetal

THE HEART

265

circulation are mixed has long been a controversial subject. The recent brilliant work of Barcroft and Barron and their co-workers has gone far toward putting some of these old controversies into proper perspective. Their first approach was through the quantitative analysis of blood samples drawn from various critical parts of the fetal circulation. The oxygen content of such samples has given important evidence as to what mixing of the currents is actually taking place in the living fetus. Later work involving the collaboration of Barclay and Franklin utilized serial x-ray photography following the injection of opaque material into the blood stream at various points. This method has given further direct evidence as to the course followed by some of the important blood currents. Synthesizing the most significant of the anatomical evidence with the newer experimental evidence, the course followed by the blood in passing through the fetal heart may be summarized somewhat as follows. The inferior caval entrance is so directed with reference to the foramen ovale that a considerable portion of its stream passes directly into the left atrium (Figs. 149 and 150). Under fluctuating pressure conditions — say following uterine contractions which send a surge of placental blood through the umbilical vein — the placental flow may temporarily hold back any blood from entering the circuit by way of either the portal vein or the inferior caval tributaries (Fig. 150). For a time, under these conditions, the left atrium would be charged almost completely with fully oxygenated blood. Such conditions, however, would be but temporary and would be counterbalanced 6y periods when the portal and systemic veins poured enough blood into the common channels to load the heart for a time with mixed or depleted blood. The ipiportant thing physiologically is not the fluctuations, but the maintenance of the average oxygen content of the blood at adequate levels.

Compared with conditions in adult mammals, the mixing of oxygenated blood freshly returned from the placenta with depleted blood returning from a circuit of the body may seem inefficient. But this is a one-sided comparison. The fetus is an organism in transition. Starting with a simple ancestral plan of structure and living an aquatic life, it attains its full heritage but slowly. It must be viewed as much in the light of the primitive conditions from which it is emerging as in comparison with the definitive conditions toward which it is progressing. Below the bird-mammal level circulatory mechanisms with partially divided and undivided hearts and correspondingly un

266

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

birth.

THE HEART

267

separated blood streams meet all the needs of metabolism and growth. Maintenance of food, oxygen, and waste products at an average level which successfully supports life does not depend on pure currents,” although such separated currents undoubtedly make for higher efficiency in the rate of interchange of materials. From a comparative viewpoint, the fact that the mammalian fetus is supported by a mixed circulation seems but natural.

Another significant fact is that careful measurements have shown that the interatrial communication in the heart of the fetus at term is considerably smaller than the inferior caval inlet. This would mean that the portion of the inferior caval stream which could not pass through this opening into the left atrium would eddy back and mix with the rest of the blood in the right atrium.

One of the most important inferences as to the fetal circulation based on vessel size is that the circulation through the lungs in a fetus which is sufficiently mature to be viable is of considerable volume. This too has now been supported by experimental work. From the standpoint of smooth postnatal circulatory readjustments, the larger the fetal pulmonary return becomes the less will be the balancing transatrial flow, and the less will be the change entailed by the assumption of lung breathing. Very early in development, before the lungs have been formed, the pulmonary return is negligible and the flow from the right atrium through the interatrial ostium primum constitutes practically the entire intake of the left atrium. After the ostium primum is closed and while the lungs are but little developed, flow through the interatrial ostium secundum must still be the major part of the blood entering the left atrium. During the latter part of fetal life the foramen ovale in septum secundum becomes the transseptal route. As the lungs grow and the pulmonary circulation increases in volume, a progressively smaller proportion of the left atrial intake comes by way of the foramen ovale and a progressively larger amount from the vessels of the growing lungs.

The balanced atrial intake thus maintained implies a balanced ventricular intake, and this in turn implies a balanced ventricular output. Although not in the heart itself, we have seen that there is in the closely associated great vessels a mechanism which affords an adequate outlet from the right ventricle during the period when the pulmonary circuit is developing. When the pulmonary arteries are formed from the sixth pair of aortic arches, the right sixth arch soon loses its original connection with the dorsal aorta. On the left, how

268

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

ever, a portion of the sixth arch persists as a large vessel connecting the pulmonary artery with the dorsal aorta (Fig^. 138 and 150). This vessel, already familiar to us as the ductus arteriosus, remains open throughout fetal life and acts as a .shunt, carrying over to the aorta whatever excess of blood the pulmonary vessels at any particular phase of their development are not prepared to receive from the right ventricle. As has already been pointed out, the ductus arteriosus can be called the “exercising channel” of the right ventricle because it makes it possible for the right ventricle to carry its full share of work throughout development and thus to be prepared for pumping all the blood through the lungs at the time of birth.

VII. The Changes in the Circulation Following Birth

The two most obvious changes which occur in the circulation at the time of birth are the abrupt cutting off of the placental blood stream and the immediate assumption by the pulmonary circulation of the function of oxygenating blood. One of the most impressive things in embryology is the perfect preparedness for this event which has been built into the very architecture of the circulatory system during its development. The shunt at the ductus arteriosus, whic ii has been one of the factors in balancing ventricular loads throughout development, and the valvular mechanism at the foramen ovale, which has at the same time been balancing atrial intakes, are perfectly adapted to effect the postnatal rebalancing of the circulation. The closure of the ductus arteriosus is the primary event and the closure of the foramen ovale follows as a logical sequel.

It has long been known that the lumen of the ductus arteriosus is gradually occluded postnatally by an overgrowth of its intimal tissue. This process in the wall of the ductus is as characteristic and regular a feature of the development of the circulatory system as the formation of the cardiac septa. Its earliest phases begin to be recognizable in the fetus as the time of birth approaches, and postnatally the process continues at an accelerated rate to terminate in complete anatomical occlusion of the lumen of the ductus about six to eight weeks after birth,

Barcroft, Barclay, and Barron have conducted an extensive series of experiments on animals delivered by Cesarean section which, indicate that the ductus arteriosus closes functionally far sooner than it does anatomically. Following birth there appears to be a contraction of the circularly disposed smooth muscle in the wall of the ductus

THE CHANGES IN THE CIRCULATION FOLLOWING BIRTH 269

which promptly reduces the flow of blood through it. This reduction in the shunt from the pulmonary circuit to the aorta, acting together with the newly assumed respiratory activity of the lungs themselves, aids in raising the pulmonary circulation promptly to full functional level. At the same time the functional closure of the ductus by muscular contraction paves the way for the ultimate anatomical obliteration of its lumen by overgrowth of intimal connective tissue. This concept of the immediate functional closure of the ductus is so appealing on theoretical grounds that a little extra caution in evaluating the evidence is indicated. It should be borne in mind that an initial tendency on the part of the circular smooth muscle of the ductus to contract does not necessarily imply a contraction sufficiently strongly and steadily maintained to shut off all blood flow during the six to eight weeks occupied by morphological closure. The dramatic quality of an immediate muscular response should not cause us to forget the importance of the slower but more positive structural closure.

The results of increased pulmonary circulation with the concomitant increase in the direct intake of the left atrium are manifested secondarily at the foramen ovale. Following birth, as the pulmonary return increases, compensatory blood flow from the right atrium to the left decreases correspondingly, and finally ceases altogether. This is indicated anatomically by a progressive reduction in the looseness of the valvula foraminis ovalis and the consequent diminution of the interatrial communication to a progressively narrower slit between the valvula and the septum. When equalization of atrial intakes has occurred, the compensating one-way valve at the foramen ovale falls into disuse, and the foramen ovale may be regarded as functionally closed.

Anatomical obliteration of the foramen ovale follows leisurely in the wake of its functional abandonment. There is a considerable interval following birth before the septum primum fuses with the septum secundum to seal the foramen ovale. This delay is, however, of no import because as long as the pulmonary circuit is normal and pressure in the left atrium does not fall below that in the right, the orifice between them is functionally inoperative. It is not uncommon to find the fusion of these two septa incomplete in the hearts of individuals who have, as far as circulatory disturbances are concerned, lived uneventfully to maturity. Such a condition can be characterized as ‘‘probe potency’’ of the foramen ovale. When, in such hearts, one inserts a probe under the margin of the fossa ovalis and pushes it

270

THE DEVELOPMENT OF THE CIRCULATORY SYSTEM

toward the left atrium one is, so to speak, prying behind the no longer used, but still unfastened, interatrial door. ,

With birth and the interruption of the placental circuit there follows the gradual fibrous involution of the umbilical vein and the umbilical arteries. The flow of blood in these vessels, of course, ceases immediately with the severing of the umbilical cord, but obliteration of the lumen is likejy to take from three to , five weeks, and isolated portions of these vessels may retain a vestigial lumen for much longer. Ultimately these vessels are reduced to fibrous cords. The old course of the umbilical vein is represented in the adult by the round ligament of the liver extending from the umbilicus through the falciform ligament, and by the ligamentum venosus within the substance of the liver. The proximal portions of the umbilical arteries are retained in reduced relative size as the hypogastric or internal iliac arteries. The fibrous cords extending from these arteries on either side of the urachus toward the umbilicus represent the remains of the more distal portions of the old umbilical arteries. They are known in the adult as the obliterated branches of the hypogastric arteries, or as the lateral umbilical ligaments.

Much yet remains to be learned as to the more precise physiology of the fetal circulation and as to the interaction of various factors during the transition from intra-uterine to postnatal conditions. Nevertheless, with our present knowledge it is quite apparent that the changes in the circulation which occur following birth involve no revolutionary disturbances of the load carried by different parts of the heart. The fact that the pulmonary circulation is already so well developed before birth means that the changes which must occur following birth are far less profound than was formerly believed ; and the compensatory mechanisms at the foramen ovale and the ductus arteriosus which have been functioning all during fetal life are entirely competent to effect the final postnatal rebalancing of the circulation with a minimum of functional disturbance. It is still true that as individuals we crowd into a few crucial moments the change from water living to air living that in phylogeny must have been spread over eons of transitional amphibious existence. But as we learn more about this change in manner of living, it becomes apparent that we should marvel more at the completeness and the perfection of the preparations for its smooth accomplishment, and dwell less on the old theme of the revolutionary character of the changes involved.

Chapter 12

Tke Histogenesis of Bone and tlie Development of tke Skeletal System

I. Histogenesis of Bone

Histologically bone belongs to the group of tissues known as the connective and supporting tissues. In spite of their widely varying adult conditions these.tissues are all similar in that the secreted parts, rather than the cells themselves, carry out the functional role characteristic of the tissues. It is the secreted, fibrous portion of the binding connective tissues which ties together various other tissues and organs ; it is the secreted matrix of cartilage and of bone which affords rigid support and protection to soft parts and furnishes a lever system on which the muscles may be brought into play.

The cellular elements of these tissues must not be overlooked, however, in emphasizing the functional importance of the cell products. The cells are, so to speak, the power behind, in that they extract the appropriate raw materials from the circulation, elaborate them within their cytoplasm, and deposit the characteristic secretion as an end-product. Moreover after the fiber is formed or the matrix is laid down, it is dependent on the cells for maintenance in a healthy active conditidn.

Embryologically the entire connective-tissue group arises from mesenchymal cells. It is not surprising, in view of their closely related functions and their derivation from a common type of ancestral cell, that one type of connective tissue may be converted into or replaced by another. This facility for changing the type of specialization is sometimes referred to as plasticity.

The plasticity of the connective-tissue series is well exemplified in the development of bone. Bone does not form in vacant spaces. It is always laid down in an area already occupied by some less highly specialized member of the connective-tissue family. The formation of some bones begins in areas already occupied by connective tissue — such bones are said to be intramembranous in origin, or are spoken

271

272 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

of as membrane bones. Other bones are laid down in areas already occupied by cartilage. In this case they are said to be pndochondral in origin, or, are called cartilage bones. It should be clearly borne in mind that these terms apply solely to the method by which a bone develops and do not imply any differences in histological structure, once the bone is fully formed.

Likewise we should know at the outset what histologists mean when they speak of cancellous bone and compact bone. These terms refer not to the method of origin of the bone but to its density when fully formed. Developmen tally all bone goes through the spongy or cancellous stage. Some bones later become compact, others remain cancellous. Most bones are compact in some areas and cancellous in others.

The subject of bone development can be presented more simply if we take up first the formation of primary cancellous bone intramembranously ; then the method by which this same type of spongy bone is formed within cartilage, and finally the changes by which cancellous bone, formed in either of the above ways, may become secondarily compact.

Intramembranous Formation of Primary Cancellous Bone. In

an area where intramembranous bone formation is about to begin we find an abundance of mesenchymal cells congregated and numerous small blood vessels present. The mesenchymal cells soon exhibit a tendency to cluster together in more or less elongated groups here and there throughout the area. If we study a group of this type which has been aggregated for a short time we can make out the beginning of a definite plan of organization. Near the axis of the cord delicate fibers appear, produced by the secretory activity of the cells. As this fibrous strand becomes more definite, the cells tend to become ranged against it (Fig. 151, A). In so doing they retract the cytoplasmic processes which are so characteristic of undifferentiated mesenchymal cells and become rounded. In this stage we have essentially a connective tissue in which the fibrous strands are for the most part rather widely separated from one another, and in which each strand has, lined up against it^ the cells responsible for its production.

The actual deposition of bone matrix begins very soon after the establishment of these primordial strands of mesenchymal cells and fibers. In fact one usually finds the formation of bone beginning on the older part of a strand while the strand itself is still being extended at one end by the aggregation of more mesenchymal cells (Fig. 151,

HISTOGENESIS OF BONE

273

I'k;. 151, Formation of trabeculae of membrane bone. Projection drawings from the mandible of a pig embryo 130 mm. in length (cf. Fig. 182).

Abbreviations: Matrix cal., ossein matrix impregnated with calcium salts; Matrix oss., ossein matrix not yet impregnated with calcium salts.

A). When the mesenchymal cells ranged against the fibrous axis of such a strand become active in the secretion of calcareous material they are spoken of as osteoblasts. We should not lose sight of the fact that they are the same cells which formed the fibrous axis of the original strands, given a new name in deference to their further specialization and altered internal chemistry.

In studying the deposition of bone matrix one must bear in mind its dual nature. The matrix consists of an organic fibrous framework which is impregnated by a subsequent deposit of inorganic calcium compounds. We may liken the matrix of bone to reinforced concrete* In the making of a road or a wall, a meshwork of steel is first placed in the forms and concrete is then poured in. The steel gives the finished structure tensile strength and a certain amount of elasticity, the concrete gives form and hardness. So in bone the organic fibers {ossein fibers) impart strength and resilience, while the calcium salts whh which the fibers are impregnated give to the completed matrix body and rigidity.

274 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

The two steps in the deposition of bone matrix may be demonstrated readily in areas where active bone forma^tion is going on, owing to the fact that the presence of calcium compounds- in a tissue markedly increases its affinity for stains. Even after most of the calcium salts have been removed from the ossein framework by treatment of the tissue with acids (decalcification) to permit the making of sections, the staining reaction is still apparent. This indicates that the ossein fibers in which calcium has once been deposited are more or less permanently changed chemically even though all the calcium possible is subsequently removed.

If we look at a strand on which the osteoblasts have been active for a time (Fig. 151, B) we see, next to the osteoblasts, a zone of bone matrix which takes very little stain. This is the newly deposited organic portion of the matrix as yet unimpregnated with calcium salts. It consists of a feltwork of minute fibers so delicate and so closely matted together that it is very difficult in ordinary preparations to see the individual fibers at all. Slightly farther from the osteoblasts the matrix is densely stained (Fig. 151, B). This part of the matrix has been impregnated with calcium salts, chiefly phosphates and carbonates, and has thereby been converted into true bone matrix. The calcium utilized by the osteoblasts in this process is brought to them by the blood stream where it is carried in soluble form, probably in organic linkage. It is interesting to note in this connection that the presence of calcium and of phosphates in the blood is not in itself all that is necessary for this process. There must be present also sufficient vitamin D, which in some way facilitates the extraction by the osteoblasts of these raw materials from the blood and their deposition in insoluble form as part of the bone matrix. The absence of vitamin D from the system results in the formation of bone matrix deficient in calcium salts and therefore lacking in rigidity — a cohdition not infrequent in pigs. Stock raisers have miscalled this condition rheumatism but it is really the same condition known medically as rickets.

In the deposition of the matrix, the fibrous core of the original strand serves as a sort of axis on which the first matrix is laid down. When such a strand is completely invested by bone matrix, it is called a trabecula (little beam). As the osteoblasts continue to secrete and thereby thicken the trabecula, the accumulation of their own product forces them farther and farther away from the axial strand about which the first of the matrix was formed. The new matrix added is not laid down uniformly. It is possible to make out in it markings

HISTOGENESIS OF BONE

275

which are suggestive of the growth rings of a tree. Apparently the osteoblasts work more or less in cycles, depositing a succession of thin layers of matrix. Each of these layers of the matrix is called a lamella (Fig. 152). As the row of osteoblasts is forced back with the deposit of each succeeding lamella, not all the cells free themselves from their secretion. Here and there a cell is left behind. As its former fellows

Erythroblast extruding nucleus

Reticular connective-tissue cell j Erythroblast in mitosis Young erythroblast

Normoblast Blood vessel .

Fat cell --tHemocytoblast —

Granuloblast - Hemocytoblast in mitosis

Polykaryocyte.

Osteoblast ^ t

I

Bone cell

Bone

lamella

Fio. 152. A small area of bone and adjacent marrow as seen in highly magnified decalcified sections. The drawing has been schematized somewhat to emphasize the relations of the cytoplasmic processes of the osteoblasts* and the bone cells so important in nutrition. In the adjacent marrow developmental stages of various types ofiiiijioQd cells, have been

continue to pile up new matrix, it becomes completely buried (Fig, 151, B). An osteoblast so caught and buried is called a bone cell {osteocyte)^ and the space in the matrix which it occupies is called a lacuna. The bone cells, thus entrapped, of necessity cease to be active bone formers, but they play a vital part in the maintenance of the bone already formed. They have delicate cytoplasmic processes radiating into the surrounding matrix through minute canalidhli. The processes of one cell come into communication with the processes of its neighbors (Fig. 152). Thus the bone cells nearer to blood vessels

276 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

Fig. 153. Diagrams showing stages in establishing of a characteristic area of primary cancellous bone by extension and coalescence of originally separate trabeculae.

absorb and hand on materials to their more remote fellows which in turn utilize these materials in maintaining a healthy condition in the organic part of the bone matrix. It is the senescence of these cells with the consequent lowering of their efficiency and the resultant deterioration of the ossein component of the matrix which is in part responsible for the decreased resiliency of the bones in advanced age.

As the various trabeculae in an area of developing bone grow, they inevitably come in contact with each other and fuse. Thus trabeculae, at first isolated, soon come to constitute a continuous system (Fig. 153). Because of its resemblance to a latticework (Latin — cancellus), bone in thb condition, where the trabeculae are slender and the spaces between them extensive, is known as cancellous bone. The spaces between the trabeculae are known as marrpw spaces.

Endochondral Bone Formation. As the term implies, endochondral bone formation goes on within cartilage. It cannot be stated too strongly that cartilage does not, in this process, become converted int# bone. Cartilage is destroyed and bone is formed where the cartilage used to be. The actual bone formation is essentially the same as in the case of membrane bone. The phenomena of special

mSTCXJENESIS OF BONE

277

interest in connection with this type of bone development are those involved in the destruction of the cartilage preliminary to the formation of bone.

Cartilage Formation. To trace the process logically we must start back with the formation of cartilage. The first indication of impending chondrogenesis is the aggregation of an exceedingly dense mass of mesenchymal cells. This cell mass gradually takes on the shape of the cartilage to be formed. The histogenetic changes involved are not at first conspicuous. During the period of preliminary massing the cells have been migrating in from surrounding regions and also increasing the local congestion by rapid proliferation. As they are packed in together they lose their processes and become rounded (Fig. 154, A, 1). When it seems as if no more cells could possibly be crowded in, the course of events changes. The cells begin to separate from one another. This is due to the fact that they have become active in

Fig. 154. Photomicrographs of developing cartilage. The areas photographed were from the margins of the paranasal cartilage of pig embryos between 25 and 30 mm. in length. For location of cartilage in head see figure 175.

A, Early stage showing: at (1) the massing of mesenchymal cells which were about to be incorporated in the growing margin of the cartilage; and at (2) an area where matrix formation is already beginning.

B, Slightly more advanced stage of the same cartilage showing: at (1) increase in the amount and density of the matrix in the center of the growing cartilage; at (2) concentration of the surrounding mesenchyme to form tire perichondrium; and at (3) the addition of new cartilage matrix peripherally*

278 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

secreting. It is the accumulation of the secretion of the cells which gradually forces them farther and farther apart unti^ they come to lie isolated from one another in the matrix they have produced (Fig. 1 54, A, 2). Such a method of increase in m^ss, where there are many scattered growth centers contributing independently to the increase in bulk of the whole, is known as interstitial growth. This interstitial growth of young cartilage stands in sharp contrast to the appositional growth of such rigid substances as bone or dentine or enamel where the matrix is laid down in successive layers one upon another. Obviously interstitial growth implies plasticity of the substance produced. Were the substance produced unyielding, the very activity of a number of growth centers within it would soon crowd those growth centers to obliteration.

As the cartilage matrix is increased in amount its affinity for basic stains becomes more marked, due probably to increase in concentration of the characteristic substance in it known chemically as chondrin. At the same time the matrix becomes more rigid with a resultant checking of interstitial growth. The cells continue to secrete to a certain extent, however, as evidenced by the fact that in mature cartilage the matrix immediately surrounding the cells becomes more dense than the rest of the matrix. This area of denser matrix around the lacuna in which the cell lies is known as the capsule. As the cartilage grows older the capsules become more conspicuous and many of them come to contain more than one cell. These nests of cells in a common capsule are the result of cell divisions, following which the daughter cells are held imprisoned in the original capsule of the mother cell — further evidence of the loss of plasticity in the matrix.

The formation of a matrix so rigid that interstitial growth is checked, takes place first centrally in an area of developing cartilage. When the center has become too rigid for interstitial growth to continue, appositional growth begins to take place peripherally. While the cartilage has been increasing in mass it has been acquiring a peripheral investment of compacted mesenchyme. This investing layer of mesenchyme soon becomes specialized into a connectivetissue covering called the perichondrium. The layer of the perichondrium next to the cartilage is less fibrous than the outer layer and the cells in it continue to proliferate rapidly and become active in the secretion of cartilage matrix. For this reason it is known as the chondrogenetic layer of the perichondrium. It is through the activity (rf the chondrogenetic layer that the cartilage continues to grow

Cartilage

ceil

Cart. trab. 1

Osteoblast

— Bone ntotrix

Bone trabecula

Periosteum

Fig. 155. Drawing showing periosteal bud and an area of endochondral bone formation from the radius of a 125 mm. sheep embryo. The small sketch indicates the location of the area drawn in detail.

Abbreviations: Cart, eros., area from which cartilage has recently been eroded; Cart, pre-eros., area with cartilage cells enlarged and arranged in rows presaging erosion; Cart, trab,, remnant of cartilage matrix which has become calcified and serves as an axis or core about which bone lamellae are deposited to form a bone trabecula; Mes., mesenchymal cell.

279

280 HISTOGENESIS OF BONE AND DEVEI.OPMENT OF SKELETAL SYSTEM

peripherally, by apposition, long after interstitial growth has ceased in the matrix first formed. ^

Cartilage Erosion. When a mass of cartilage is about to be replaced by bone, very striking changes in its structure take place. The cells which have hitherto been secreting cartilage matrix begin to destroy the matrix. The lacunae become enlarged and a curious arrangement of the cartilage cells becomes evident. The cells erode the cartilage in such a manner that they become lined up in rows (Fig. 155). This process of destruction continues until the cartilage is extensively honeycombed. Meanwhile the tissue of the perichondrium overlying the area of cartilage erosion becomes exceedingly active. There is rapid cell proliferation and the new cells, carrying blood vessels with them, begin to invade the honeycombed cartilage (Fig. 155).

The Deposition of Bone. It is a striking fact that during its growth cartilage is devoid of blood vessels, the nearest vessels to it being those in the perichondrium. The invasion of cartilage by blood vessels definitely determines its disintegration as cartilage, and at the same time is the initial step in the formation of bone. For this reason the enveloping layer of connective tissue, up to this time called perichondrium because of its relation to the cartilage, is now called periosteum because of the relations it will directly acquire to the bone about to be formed. This change will not be confusing if we stop to think that both these terms are merely ones of relation, which translated mean, respectively, that tissue which surrounds cartilage, and that tissue which surrounds bone. The important fact to bear in mind is that this enveloping layer of tissue is of mesenchymal origin and therefore contains cells of the stock that may develop into any of the connectivetissue family to which bone as well as cartilage belongs. When, therefore, a mass of periosteal tissue {periosteal bud, Fig. 155) grows into an area of honeycombed cartilage it carries in potentially boneforming cells. These cells come to lie along the strand-like remnants of cartilage, just as in membrane bone formation osteoblasts ranged themselves along fibrous strands. The actual deposition of bone proceeds in the same manner endochondrally as it does intramembranously. The only difference is that in one case a strand-like remnant of cartilage serves as an axis for the trabecula, whereas in the other case deposition begins on a fibrous strand. Extensions and fusions of the growing trabeculae soon result in the establishment of typical cancellous bone similar to that formed intramembranously.

HISTOGENESIS OF BONE

281

The Formation of G)mpact Bone from Primary Cancellous Bone. The difference between cancellous bone and compact bone is architectural rather than histological. The fundamental composition of the bone matrix, its lamellation, and the relations of the bone cells to the matrix, are the same in both cases. It is the way in which the lamellae are arranged that distinguishes these two types of bone from each other. In cancellous bone the disposition of lamellae is such that it leaves large marrow spaces between the trabeculae. In compact bone there has been a secondary deposit of concentrically arranged lamellae in the marrow spaces which greatly increases the density of the bone as a whole.

The essential differences between the two, and the way in which cancellous bone may become converted into compact bone, can be illustrated by a simple schematic diagram. Figure 156, 1, shows the arrangement of lamellae and marrow spaces in primary cancellous bone. The osteoblasts which have formed the trabeculae still lie along them on the surface toward the marrow cavity. If such an area is to IxTome compact, these osteoblasts enter on a period of renewed activity and deposit a series of concentric lamellae in the marrow cavity. Frequently if the marrow spaces are irregular there is a preliminary rounding out of them by local resorption of the bone already formed (Fig. 156, 2). This is then followed by the deposition

Fig. 156. Diagram showing transformation of cancellous to compact bone. The solid lines indicate the lamellae of primary cancellous bone; the dotted lines show the subsequently added concentric (Haversian) lamellae which nearly obliterate the marrow spaces of cancellous bone. The sequence of events is indicated by the numbers. Note that irregularly shaped spaces in the cancellous bone may be rounded out by absorption before the concentric lamellae are laid down.

282 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

of the concentrically arranged lamellae, sometimes called Haversian lamellae after the man who first described them in detail (Fig. 156, 3 ). In this process the original marrow spaces are reduced to small canals {Haversian canals^ into which have been crowded the blood vessels which formerly lay in the marrow cavities (Fig. 156, 4 ). These canals maintain intercommunication with each other in the substance of the bone, constituting a network of pathways over which the bone receives its vascular supply. As compared with the marrow spaces of cancellous bone, however, they are very small; and the gross appearance of a bone which has undergone this secondary deposit of concentric lamellae amply justifies characterizing it as ‘'compact.’’

II. The Development of the Skeletal System

In dealing with the development of the skeletal system we must recognize at the outset that the subject is far too extensive to be covered here with anything like completeness. It is not difficult, however, to become acquainted with the outstanding features in the development of two or three characteristic bones, as, for example: the sequence of events in the formation of a flat bone; the steps involved in the establishment and growth of a long bone; the way separate ossification centers appear in a common primordial cartilage mass and give rise to the various parts of a vertebra. Familiarity with such type processes gives one an understanding of the factors operative in the development of the skeleton as a whole and a background sufficient to permit ready and intelligent following up of developmental details in specific bones in which one may become interested.

Development of Flat Bones. The flat bones, such as the bones of the cranium and face, are for the most part of intramembranous origin. We are, therefore, already familiar with the early steps in their development from our study of the histogenesis of membrane bone (Figs. 151 and 153). After a mass of primary cancellous bone has been laid down in a configuration which suggests that of the adult bone being formed, there appears about this mass a peripheral concentration of mesenchyme (Fig. 157, A). This periosteal concentration of mesenchymal tissue contains potentially bone-forming cells which soon become active and lay down a dense layer of parallel lamellae about the spongy center of the growing bone (Fig. 157, B). Anatomically this dense peripheral portion is known as the outer table of the bone. The inner portion, which in the flat bones usually remains cancellous, is called the diploii. The original mesenchymal tissue which

THE DEVELOPMENT OF THE SKELETAL SYSTEM

283

Periosteum Marrow space

l^one trabeculae

A

Subperiosteal bone lamellae

Bone trabeculae Marrow space

Periosteum

Fig. 157. Diagrams showing the manner in which the dense peripheral layer of a flat bone is formed by the deposition of subperiosteal lamellae about an area of primary cancellous bone.

I

remains in the marrow spaces of the diploe develops into characteristic “red bone marrow” rich in blood-forming elements (Fig. 152).

The story of the growth of the mandible, a membrane bone which starts after the manner of flat bones but which later takes on a very elaborate shape and finally becomes largely compact, can be gleaned by a comparative study of figures 178, 180, and 184.

Development of Long Bones. The long bones are characteristically of endochondral origin. The cartilage in which they are performed is a tempiorary miniature of the adult bone. Ordinarily there are several ossification centers involved in the formation of long bones. The first one to appiear is that in the shaft or diaphysis. The location of this center is shown schematically in figure 158, A, Such

B

284 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

b

A

Fig. 158, Diagrams showing liie progress of ossification in a long bone. The stippled areas represent cartilage; the black areas indicate bone.

A, Primary ossification center in shaft. B, Primary center plus shell of subperiosteal bone. C, Entire shaft ossified. D, Ossification centers have appeared in the epiphyses. E, Entire bone ossified except for the epiphyseal cartilage plates.

details as the cartilage erosion which preceded its appearance and the manner in which the deposit of bone was initiated have already been considered (Fig. 155). Our interest now is in the relation of such an endochondral ossification center to other centers, and to the bone as a whole.

Almost coincidently with the beginning of bone formation within the cartilage the overlying periosteum begins to add bone externally (Fig. 158, B). In view of the fact that the bone-forming tissue carried into the eroded cartilage arose from the periosteum, this activity of the periosteum itself is not surprising. Moreover we have already encountered this same phenomenon of periosteal bone formation in the outer table of flat bones.

The formation of bone which starts at about the middle of the shaft soon extends toward either end until the entire shaft is involved (Fig. 158, C), leaving the two ends {epiphyses) still cartilage. Toward the end of fetal life ossification centers appear in the epiphyses. The number and location of these epiphyseal centers vary in different long bones. There is always at least one center in each epiphysis and there may be two or more. Not uncommonly there are two centers in one epiphysis and one in the other, as illustrated in figure 158, D.

Between the bone fojcmed in the diaphysis and that formed in the epiphysis there persists a mass of cartilage known as the epiphyseal plaie which is of vital importance in the growth in length of the bone.

THE DEVELOPMENT OF THE SKELETAL SYSTEM

285

We should expect from the rigidity of bone matrix that interstitial growth could not account for its increase in length. This was long ago demonstrated experimentally by exposing a developing bone and driving into it three small silver pegs, two in the shaft and one in the epiphysis. The distance between the pegs being recorded, the incision was closed and development allowed to proceed until a marked increase had occurred in the length of the bone. On again exposing the pegs, the two in the shaft were found to be exactly the same distance apart as when they were driven in, but the distance between the pins in the shaft and that in the epiphysis had increased by an amount corresponding to the increase in length of the bone. This indicates clearly that the epiphyseal plates constitute a sort of temporary, plastic union between the parts of the growing bone. Continued increase in the length of the shaft is accomplished by the addition of new bone at the cartilage plate. These epiphyseal plates persist during the entire postnatal growth period. Only when the skeleton has acquired its adult size do they finally become eroded and replaced by bone which joins the epiphyses permanently to the diaphysis.

As the bone increases in length there is a corresponding increase in its diameter. The manner in which this takes place is also susceptible of experimental demonstration. If madder leaves, or some of the alizarin compounds extracted from them, be fed to a growing animal, the bone formed during the time the feeding is continued is colored red. If the madder is discontinued, bone of normal color is again formed ; but the color still remains in the bone laid down while madder was being added to the diet. Thus it is possible, by keeping a record of alternate f>eriods of feeding and withholding madder and comparing these records with the resulting zones of coloration in a bone, to obtain very accurate information on the progress of bone growth and resorption. Applied to the development of long bones this method shows their increase in diameter to be due to continued appositional growth beneath the periosteum. As the bone is added to peripherally there is a corresponding resorption centrally. This central resorption results in the formation of a cavity in the axis of the long bone which is called the marrow canal (Fig. 158, C). With the further increase in the diameter of a bone, its marrow canal becomes correspondingly enlarged. A significant mechanical fact might be cited in this connection. 'Engineers have determined that the strongest rod which can be made from a given weight of steel is obtained by molding it into tubular form. The development of an essentially tubular shaft by

286 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

progressive increase in the size of the marrow cavity gjivcs a long bone maximum strength with minimum weight.

The Formation of the Vertebrae. The development of the vertebrae is of interest to the student primarily because it exemplifies so excellently a fundamental embryological phenomenon — the origin of separate parts from an undifferentiated primordial tissue mass, and the subsequent association of these parts to form an organized structure. In studying young embryos we traced the history of the mesodermic somites through their early differentiation. It will be recalled that from the ventro-mesial face of each somite there arises a group of mesenchymal cells called collectively a sclerotome (Fig. 42). These cells migrate from either side toward the mid-line and become aggregated about the notochord. From these masses of cells the entire vertebral column is destined to arise.

The first significant change which takes place in these primordial masses is the clustering of sclerotomal cells derived in part from each of the two adjacent somites into groups which are located opposite the intervals between the myotomes. In studying series of transverse sections this arrangement is easy to overlook unless the density of the cells about the notochord is carefully noted in passing from section to section. It shows very clearly, however, in frontal sections (Fig. 159). Each of these cell clusters is the primordium of the centrum of a vertebra. Once formed they rapidly become more dense and more definitely circumscribed (Fig. 160). Soon after the centrum takes shape, paired mesenchymal concentrations extending dorsally and laterally from the centrum establish the primordia of the neural arches and of the ribs (Fig. 161).

Fig. 159. Semi-schematic coronal sections through the dorsal region of young embryos to show how the vertebrae became intermyotomal in position. Note that the primordium of a centrum is formed by cells originating from the sclerotomes of both the adjacent pairs of somites.

THE DEVELOPMENT OF THE SKELETAL SYSTEM

287

Fig. 160. Transverse section from pig cm])ryo of 17 mm. cut at the level of the lungs to show the structures in the dorsal body-wall. (After Minot.)

mantle layer ependymal

marginal layer of eord

neural arch

of cord

layer

eympathetic ganghon anterior cardinal vein

left left duct erihre fetdium vt Ctteter

Fig. 161 . Transverse section of 20 mm. pig embryo cut at the level of the lungs to show the developing vertebra and ribs. (After Minot.)

288 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

Fig. 162. Transverse section from 40 mm. pig embryo cut at the level of the lungs to show the developing vertebra and ribs.

The Stage in w^hich the various parts of the vertebrae arc sketched in mesenchymal concentrations, is frequently spoken of as the blastemal stage. It is rapidly followed by th^ cartilage stage. Conversion to cartilage begins in the blastemal mass first in the region of the centrum and then chondrification centers appear in each neural and each costal process (Fig. 161). These spread rapidly until all the centers fuse and the entire mass is involved (Fig. 162). The cartilage miniature of the vertebra thus formed is at first a single piece showing no lines of demarcation where the original centers of cartilage formation became confluent, and no foreshadowing of the separate parts of which it will be made up after the cartilage has been replaced by bone. Shortly before ossification begins the rib cartilage becomes separated from the vertebra, but the vertebra itself remains in one piece throughout the cartilage stage (Fig. 162).

The locations of the endochondral ossification centers which appear in a vertebral cartilage are indicated schematically in figure 163. It readily can be seen how the spreading of these centers of bone formation will establish the conditions which exist in an adult vertebra. The median ossification center gives rise to the centrum. The centers in the neural processes extend dorsally to complete the neural arch. The spinous process in most of the vertebrae is formed by a prolongation of these same centers to meet dorsal to the neural canal.

Fig. 164. Diagram of four types of vertebrae indicating the parts derived from the different ossification centers shown in figure 163. The part formed by the median center in centrum is cdncentrically ringed; the parts arising from the costal centers are stippled; parts derived from the lateral centers in the neural arches are indicated in line-shading,

289

290 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

In forms such as the pig the spinous processes of tl>e more anterior thoracic vertebrae are very long. In these vertebrae additional ossification centers appear in the spinous process and fuse with those in the

Scapula Humerus

Radius Mandible

& ulna

Fig. 165. Photograph (X 1/^ showing the ossification centers which have appeared in pig embryos of 35 mm. This and the two following figures were made by photographing in transmitted light embryos in which all the uncalcified tissues had been rendered transparent by treatment with potassium hydroxide and glycerine.

neural processes. The transverse processes with which the tubercles of the ribs articulate are formed by the lateral extension of the primary ossification centers in the neural processes. These same centers extend ventrally also, and meet the centrum (cf. Figs. 163 and 164).

Scapula / Humerus

Fic. 166. Photograph (X IM) showing the progress of ossification in the skeleton of a 65 mm. pig embryo.

Fig. 167. Photograph {X showing the extent of ossification in the skeleton of a 90 nun. pig embryo.

292 HISTOGENESIS OF BONE AND DEVELOPMENT OF SKELETAL SYSTEM

The shaft of the rib is formed by extension of its primary ossification center (Fig. 163). After birth, secondary epiphyseal centers appear in the tubercle and head of the rib. These centers are separated from the shaft by persistent cartilage plates in the manner described in discussing the development of long bones. Fusion of the secondary epiphyseal centers with the shaft of the rib does not take place until the skeleton has acquired its adult dimensions.

The foregoing discussion has been based on a thoracic vertebra in which the relations of the rib to the vertebra show most clearly. All the vertebrae have the costal element represented, although it is greatly reduced and modified in other regions than the thoracic. A study of figure 164, in which the components of vertebrae from the cervical, thoracic, lumbar, and sacral regions are schematically indicated, will make the homologies apparent. With these homologies in mind it is sufficiently evident, without going into further detail, how all these vertebrae arise by a process similar to that described for the thoracic vertebrae.

The Progress of Ossification in the Skeleton as a Whole. It

would carry us beyond the scope of this book to take up the development of specific bones. Each has its own story involving the formation of the connective tissue or the cartilage mass which precedes it ; local erosion centers if it be preformed in cartilage; number, location, and time of appearance of ossification centers; growth in length and diameter; development of epiphyses; time of fusion of epiphyses and diaphysis; and finally the development of muscle ridges and articular facets. Without entering into a discussion of details of this sort, it is possible nevertheless to follow the general progress of ossification in the skeletal system as a whole. Embryos which have been treated with potassium hydroxide and then cleared in glycerine clearly show the various ossification centers. In such preparations the areas where calcium salts have been deposited stand out white in reflected light and opaque in transmitted light. ^Figures 165-167, which are photographs of preparations of this type, can be used to trace the history of the more important bones. It should perhaps be stated explicitly that these figures arc included primarily to give a general view of the progress of ossification and secondarily to afford a readily available source of reference for following up points of interest that may arise. It is not a profitable use of the student’s time to attempt to memorize the ossification centers which have appeared in embryos of any given age.

Chapter 13

Tke Development of tke Face and Jaws and tke Teetk

I. The Face and Jaws

The Stomodaeum. In studying the early development of the digestive tract we saw that the primitive gut first appeared as a cavity which was blind at both its anterior and posterior ends (Fig. 37). Its opening in the future oral region is established by the meeting of an ectodermal depression, the stomodaeum, with the cephalically growing anterior end of the gut. The stomodaeal depression, even as late as the time the oral plate ruptures and establishes communication between the anterior end of the gut and the outside world, is very shallow (Fig. 40). The deep oral cavity characteristic of the adult is formed by the forward growth of structures about the margins of the stomodaeum. Some idea of the extent of this forward growth can be gained from the fact that the tonsillar region of the adult is at about the level occupied by the stomodaeal plate when it ruptures. The growth of the structures bordering the stomodaeum, then, not only gives rise to the superficial parts of the face and jaws, but actually builds out the walls of the oral cavity itself.

The Jaws. Because the face of a young embryo is pressed against the thorax it is difficult to study unless the entire head is cut off and mounted separately. Preparations of this kind observed under a dissecting microscope by strong reflected light show the surface configuration of the facial region very clearly. The most conspicuous landmarks are the stomodaeal depression, which in view of its fate we may now call the oral cavity, and the olfactory pits. In embryos as small as 7 mm. most of the structures which take part in the formation of the face and jaws are already clearly distinguishable (Fig. 168). In the mid-line cephalic to the oral cavity is a rounded overhanging prominence known as the Jrontal process. On either side of the frontal process are horseshoe-shaped elevations surrounding the olfactory pits. The

293

294

DEVELOPMENT OF FACE, JAWS AND TEETH

median limbs of these elevations are known as the nap-medial processes and the lateral limbs are called the naso-lateral processes.

Growing toward the mid-line from the cephalo-lateral angles of the oral cavity are the maxillary processes. In lateral views of the head (Figs. 31 and 32) it will be seen that the maxillary processes and the mandibular arch merge with each other at the angles of the mouth. Thus the structures which border the oral cavity cephalically are: the unpaired frontal process in the mid-line, the paired nasal processes on either side of the frontal, and the paired maxillary

Fig. 168. Face of 7 mm. pig embryo photographed X 15. Note especially the unmistakably paired character of the thickenings which later fuse in the mid-line to complete the mandibular arch.

processes at the extreme lateral angles. From these primitive tissue masses the upper jaw and the nose are derived.

The caudal boundary of the oral cavity is less complex, being constituted by the mandibular arch alone. In very young embryos (Fig. 168) the origin of the mandibular arch from paired primordia is still clearly evident. Appearing first on either side of the mid-line are marked local thickenings due to the rapid proliferation of mesenchymal tissue. Until these thickenings have extended from either side to meet in the mid-line there remains a conspicuous mesial notch. With their fusion, the arch of the lower jaw is completed (Figs. 1 69172).

THE FACE AND JAWS

295

In 10-12 mm. embryos (Fig. 169) very marked progress can be seen in the development of the facial region. The maxillary processes are much more prominent and have grown toward the mid-line, crowding the nasal processes closer to each other. The nasal processes have grown so extensively that the frontal process between them is completely overshadowed (cf. Figs. 168 and 169). The growth of the

Fig. 169. Face of 11 ,5 mm. pig embryo photographed X 12. Fusion of the right and left components of the mandibular arch is practically complete. Both the medial and lateral limbs of the horseshoe-shaped nasal processes have undergone conspicuous enlargement. Note especially the approximation of each naso-medial process to the maxillary process of the same side.

medial limbs of the nasal processes has been especially marked and they appear almost in contact with the maxillary processes on either side.

The groundwork for the formation of the upper jaw is now well laid down. Its arch is completed by the fusion of the two nasomedial processes with each other in the mid-line, and with the maxillary processes laterally (Fig. 170), The premaxillary bones carrying the incisor teeth are formed, later, in the part of the upper jaw which is of naso-medial origin. The maxillary bones, carrying all

296

DEVELOPMENT OF FACE, JAWS AND TEETH

the upper teeth posterior to the incisors, are developed in the part of the arch arising from the maxillary processes.

Nasal Chambers. The olfactory pits have by this time become much deepened, not only by the growth of the nasal processes about them, but also by extension of the original pits themselves which soon break through into the oral cavity (Figs. 93 and 97, C). We may now

lateral process

naso*‘ medial process

tojngue

hyomandibular

cleft

hyoid arch

Fig. 170. Face of 16 mm. pig embryo photographed X 10. The naso-medial processes have fused with the maxillary processes on either side, and with each other in the mid-line, thus completing the arch of the upper jaw.

speak of the external openings of the nasal pits as the nostrils {external nares) and their new openings into the oral cavity as posterior nares or nasal choanae. The septum of the nose is formed by fusion in the midline of the original naso-medial processes'; the upper part of the bridge of the nose is derived from the frontal process; and the alae of the nose arise from the naso-lateral processes (Fig. 172).

Naao-Iacrimal Duct. Where the naso-lateral process and the maxillary process meet each other there is formed iot a time a well

THE FACE AND JAWS

297

Fir;. 171. Face of 17.5 mm. pig embryo photographed X 10. The originally separate processes have now largely lost their identity in the series of fusions which have taken place in the formation of the face.

marked groove, which extends to the mesial angle of the eye (Fig. 169). This is known as the naso4acrimal groove. It soon closes over superficially (Fig. 171), and it is usually stated that the deep portion of the original groove is converted into a tube, the naso-lacrimal duct^ or tear duct, wjhich drains the fluid from the conjunctival sac of the eye into the nose. Recently Politzer has maintained that the nasolacrimal duct arises as an independent epithelial downgrowth from the conjunctival sac which follows closely along the line of closure of the old naso-optic furrow.

Tongue. While these changes are going on externally, the tongue is being formed in the floor of the mouth. Anatomically the tongue is usually described as consisting of a freely movable part called its body, and a less freely movable portion, called its root, by which it is attached in the oro-pharyngeal floor. The body of the tongue arises from a small median elevation, the tuberculum impar^ and paired lateral lingual primordia. These elevations appear very early in development on the inner face of the first branchial (mandibular) arch (Fig. 173, B). The tuberculum impar grows slowly and is soon crowded in on

298

DEVELOPMENT OF FACE, JAWS AND TEETH

by the more rapidly growing lateral lingual primordia which form the great bulk of the body of the tongue (Fig. 173, c5.

Fig. 172. Face of 21.5 rum. pig embryo photographed X 10. The characteristic features of the adult face are even at this early stage clearly recognizable. The regions of the upper jaw and nose which have arisen from originally distinct primordia are differentiated by shading. Vertical hatching indicates origin from frontal process; stippling, from naso-lateral processes; small crosses, from naso-medial processes; horizontal hatching, from maxillary processes. The entire lower jaw is derived from the mandibular arch.

Arising in the pharyngeal floor at the bases of the second and third branchial arches is an elevation known as the copula (i.e., yoke)

THE FACE AND JAWS

299

because of the way it joins these arches together (Fig. 173, B). The copula, supplemented by some tissue from the adjacent basal portions of branchial arches 2, 3, and 4, gives rise to the root of the tongue.

All the various elevations which thus take part in the formation

- Branchial arch i

-Branchial arch 2

'Branchial arch 3 .Branchial arch 4 -Glottis

Lateral lingual anlagt

Copula

Epiglottis

Glottis

Branchial arch i Lateral lingual anlage

Branchial arch $

Branchial arch 4

Arytenoid ridge

c

Fio. 173. Dissections of pig embryos made to expose the floor of the mouth and show the development of the tongue. (After Prentiss.) A, 7 mm.; B, 9 mm.; C, 13 mm. (All figures X 12.)

B

Tuherculum impof

Branchial arch 2

Epiglottis

Glottis

Lateral lingual anlage Tuherculum impar

Epiglottis Arytenoid ridge

Branchial arch i Tuherculum impar

Branchial arch 2

Branchial arch 3 Branchial arch 4

Arytenoid ridge

300

DEVELOPMENT OF FACE, JAWS AND TEETH

THE FACE AND JAWS

301

of the tongue must be thought of as composed of an outer covering and the underlying mesodermal tissue which causes the covering to bulge into the lumen. The covering tissue arises in situ from the lining of the branchial arches involved. The sensory innervation of the surface of the tongue is, therefore, just what one would expect from the basic relations of the cranial nerves to the branchial arches. The epithelium of the body of the tongue gets its sensory supply from the lingual branch of the mandibular division of the trigeminal (V) nerve (Fig. 97, A, B), and from the chorda tympani branch of the seventh nerve. The root of the longue receives its sensory fibers from the glossopharyngeal (Fig. 94) and vagus nerves.

The skeletal muscle that makes up the main mass of the tongue beneath the mucosal covering is derived from mesodermal cell masses that are believed to migrate into the pharyngeal floor from the myotomes of the occipital somites. Ontogenetically, in mammalian embryos this migration is exceedingly difficult to trace, for the cells of myotomal origin early mingle indistinguishably with the local mesenchymal cells. Nevertheless the way the hypoglossal nerve (XII), which is the cranial nerve arising at the level of these occipital myotonies, grows in with the developing lingual muscles (Figs. 93, 94, and 97, A, B) and innervates them, furnishes strong circumstantial evidence for this interpretation of tongue muscle origin and migration.

Palate. Coincidently also the palatal shelf is being formed in the upper jaw and separating off the more cephalic portion of the original stomodaeal chamber. Since it is into this cephalic portion of the cavity that the nasal pits break through (Figs. 93 and 97, C), the formation of the palatal shelf in effect prolongs the nasal chambers backwards so they open eventually into the region where the oral cavity becomes continuous with the pharynx.

The palate as well as the arch of the upper jaw is contributed to by both the naso-medial processes and the maxillary processes. From the premaxillary region a small triangular median portion of the palate is formed (Fig. 174). The main portion of the palate is derived from the maxillary processes. From them shelf-like outgrowths arise

Fig. 1 74. Photographs (X 6) of dissections of pig embryos made to expose the roof of the mouth and show the development of the palate. A, 20.5 mm.; B, 25 mm.; C, 26.5 mm.; D, 29.5 mm.

The diagrams of transverse sections are set in to show the relations before (E) and after (F) the retraction of the tongue from between the palatine processes.

302

DEVELOPMENT OF FACE, JAWS AND TEETH

on either side and extend toward the mid-line (Fig. 174, A— G). When these palatal shelves first start to develop, the tongue lies between them (Fig. 174, E). As development progresses the tongue drops down (Fig. 174, F); the palatal shelves are extended toward the mid -line and finally fuse with each other medially and with the premaxillary process anteriorly to complete the palate (Fig. 174, D). At the same time the nasal septum grows toward the palate and becomes fused to its cephalic face (Figs. 174, F, and 178). Thus the separation of

Fig. 175. Transverse section of snout of 28 mm. pig embryo (X 12). The area included in the rectangle is shown in detail in the following figure.

right and left nasal chambers from each other is accomplished at the same time that the nasal region as a whole is separated from the oral.

II. The Development of the Teeth

The Dental Ledge. Local changes leading toward tooth formation can be made out in the jaws of embryos as small as 1 5 mm. or even less. By the time a size of 28-30 mm. has been attained, a definite thickening of the oral epithelium can readily be seen on both the upper and the lower jaw. This band of epithelial cells which pushes into the underlying mesenchyme around the entire arc of each jaw is known as the labi<Hlental ledge {labio-dental lamina) (Figs. 175 and 176). Shortly after its first appearance, cross-sections show this ledge

THE DEVELOPMENT OF THE TEETH

303

of epithelial cells to be differentiating into two parts, a more distal part which by its ingrowth marks off the elevation which is to become

Fig. 176. Drawing (X 130) showing labio-dental ledge of 28 mm. pig embryo. For location of area represented see preceding figure.

Fig. 177. Drawing (X 130) showing differentiation of the labio-dental ledge into labio-gingival lamina and dental ledge.

The ingrowth of the labio-gingival lamina initiates the separation of the lip from the gum (gingiva). From the dental ledge a series of local bud-like outgrowths are formed, each of which gives rise to the enamel cap of a tooth.

The region shown is the same as that in the preceding figure but from a slightly older (37 mm.) embryo.

the lip from that which is to become the gum, and a more proximal part which is destined to grow into the gum and give rise to the enamel-forming organs of the teeth. The part of the original labio

304

DEVELOPMENT OF FACE, JAWS AND TEETH

dental ledge which separates the lip from the gum (gingiva) is known as the labio-gingival lamina^ and the part of the original ledge which is to take part in tooth formation is known as the denial ledge or dental lamina (Fig. 177).

Enamel Organs. Soon after the dental ledge is established, local buds arise from it at each point where a tooth is destined to be formed. Since these cell masses give rise to the enamel crown of the tooth they are termed enamel organs. As would be expected, the enamel organs

nasal bone

cartilage of

nasal septum

nasal

chamber

nasal process

of premaxilla

dental papilla enamel organ

labiogingival

lamina

Meckel’s cartilage

tooth germ

mandible

Fig. 178. Drawing (X 10)tDf a transverse .section of the snout of a 71 mm. pig embryo. The area included in the rectangle is shown in detail in the following figure.

for the milk teeth are budded off from the dental ledge first, but the cell clusters which later give rise to the enamel of the permanent teeth are formed at a surprisingly early time (Fig. 180). They remain dormant, however, during the growth period of the milk teeth and begin to develop actively only after the jaws have enlarged sufficiently to accommodate the permanent dentition.

The histogenetic processes involved in the formation of milk teeth and permanent teeth are essentially the same. It is, therefore, sufficient to trace them in the case of the milk teeth only, keeping in mind that the same process is repeated later in life in the formation of the permanent teeth.

In a section of the developing mandible which cuts the dental ledge

THE DEVELOPMENT OF THE TEETH

305

at a point where an enamel organ is being formed, the shape of the enamel organ suggests that of an irregularly shaped, inverted goblet, the section of the dental ledge appearing somewhat like a distorted stem (Fig. 178). The epithelial cells lining the inside of the goblet early take on a columnar shape. Because they constitute the layer which secretes the enamel cap of the tooth, they are called ameloblasts (enamel

formers) (Fig. 179). The outer layer of the enamel organ is made up of closely packed cells which are at first polyhedral in shape but which soon, with the rapid growth of the enamel organ, become flattened. They constitute the so-called outer epithelium of the enamel organ (Fig. 179). Between the outer epithelium and the ameloblast layer is a loosely aggregated mass of ceils called collectively, because of their characteristic appearance, the enamel pulp or the stellate reticulum (Fig. 179).

306

DEVELOPMENT OF FACE, JAWS AND TEETH

Fig. 180. Developing tooth from lower jaw of a 120 mm. pig embryo (X 14). The small sketch including half of the tongue (left) and part of the lip (right) gives the relations of the region drawn. The area in the rectangle is shown in detail in the following figure.

Fig, 181. Projection drawing (X 350) of segment of enamel organ and adjacent pulp from a 120 mm. pig embryo to show ameloblast and odontoblast layers. For location of area represented see preceding figure.

THE DEVELOPMENT OF THE TEETH

307

The Dental Papilla. Inside the goblet-shaped enamel organ there is caught a mass of mesenchymal cells which are said to constitute the dental papilla (Fig. 179). The cells of the dental papilla proliferate rapidly and soon form a very dense aggregation. The outer cells of this mass are destined to secrete the dentine of the tooth and the inner cells to give rise to the pulp of the tooth.

A little later in development the enamel organ begins to assume the shape characteristic of the crown of the tooth it is to lay down (Fig. 180). At the same time the outer cells of the dental papilla take on a columnar form similar to that of the ameloblasts (Fig. 181). They are now called odontoblasts (dentine formers) because they are about to become active in secreting the dentine of the tooth.

In the central portion of the dental papilla vessels and nerves arc beginning to make their appearance so that the picture is already suggestive of the condition seen in the pulp of an adult tooth. Meanwhile the growth of the dental papilla toward the gum has crowded the stellate reticulum of the enamel organ in the crown region so it is nearly obliterated (Fig. 180). This brings the ameloblasts of this region much closer to the many small blood vessels which lie in the surrounding mesenchyme. The approach of the ameloblasts to the neighboring vascular supply would appear to be significant, since it is precisely here at the tip of the crown where the ameloblasts first begin to secrete enamel (Fig. 182).

By the time the enamel organ has been well established the dental ledge has lost its connection with the oral epithelium, although traces of it can still be identified in the mesenchyme at the lingual side of the tooth germ (Fig. 180). The cluster of cells which is destined to give rise to the enamel organ of the permanent tooth of this level can be seen budding off from the ledge close to the point from which the enamel organ of ffie milk tooth arose (Figi >^).

Formation of Dentine. With these preparatory developments complete, the tooth-forming structures are, so to speak, ready to go about the fabrication of dentine and enamel. As is the case with bone, enamel and dentine are both composed of an organic basis in which inorganic compounds are deposited. We may use the same comparison that was used in describing bone : that of the familiar use in construction operations of a steel meshwork into which concrete is poured, the steel giving the finished structure some degree of elasticity and increasing the tensile strength while the concrete gives body and solidity. In the case of such hard structures in the body as bone, dentine, and

308

DEVELOPMENT OF FACE, JAWS AND lEETH

pr^ordiutn enamel organ ' permanent tooth

odontoblast layer pulp of tooth

enamel pulp (stellate reticulum) periosteum of alveolar socket outer epithelium of enamel organ

Fig. 182. Developing tooth from lower jaw of a 130 mm. pig embryo (X 30). The small sketch gives the relations of the regions drawn. The area in the rectangle is shown in detail in the following figure.

blood vessel dentine enamel blood vessel in

1 i, 1 mesenchyme

fiber lirocess of enamel organ

Fio, 183. Projection drawing (X 350) of small segment of developing

THE DEVELOPMENT OF THE TEETH

309

enamel, these interlacing organic strands in the matrix give the tissue its resilience and tensile strength, and the calcareous compounds deposited in the organic framework give form and hardness.

Although bone, dentine, and enamel are similar in having both organic and inorganic constituents in their matrix they are quite different in detail, both as to composition and microscopical structure. Bone has approximately 45 per cent of organic material while dentine has but 30 per cent and adult enamel 5 per cent or less. There is also considerable difference in the kind and proportion of inorganic compounds present in each. Structurally they are totally unlike. Bone matrix is formed in lamellae and has cells scattered through it. Dentine is formed without lam^llation and has its cellular elements lying against one face and sending long processes into tubules in the matrix. Enamel is prismatic in structure and the cells which form it lie against its outer surface while it is being deposited, but are destroyed in the eruption of the tooth.

The first dentine is deposited against the inner face of the enamel organ, the odontoblasts drawing their raw materials from the small vessels in the pulp and secreting their finished product toward the enamel organ. It is significant in this connection that in an active odontoblast the nucleus, which is the metabolic center of the cell, has gravitated toward the source of supplies and come to lie in the extreme pulpal end of the cell (Fig, 183). Also, the end of the odontoblast toward the enamel organ, where the elaborated product of the cell is being accumulated preparatory to its extrusion, can be seen to take the stain especially intensely. Although our knowledge of intracellular chemistry is as yet exceedingly fragmentary and we do not know the exact chemical nature of the product in this stage, the staining reaction is clearly indicative of the presence of calcium compounds of some sort.

If attention is turned now to the recently formed dentine, two zones distinctly different in staining reaction can be seen. The zone nearer the cells is pale, taking but little stain (Fig. 183). This zone consists of the recently deposited organic part of the matrix not as yet impregnated with calcareous material. The zone nearer the enamel organ will be found, by contrast, very intensely stained. This is the older part of the dentine matrix which has had the organic framework impregnated with calcareous material.

As the odontoblasts continue to secrete additional dentine matrix the accumulation of their own product inevitably forces the cell

310

DEVELOPMENT OF FACE, JAWS AND TEETH

layer back, away from the material previously deposited. Apparently strands of their cytoplasm become embedded in the material first laid down and are then pulled out to form the characteristic processes of the odontoblasts known as the dentinal fibers (Fig. 183). As the layer of secreted material becomes thicker and the cells are forced farther from the material first deposited, these dentinal fibers become progressively longer. Even in adult teeth where the dentine may be as much as 2 mm. in thickness they extend from the odontoblasts which line the pulp chamber to the very outer part of the dentine. These dentinal fibers are believed to be concerned with maintaining the organic portion of the dentine matrix in a healthy condition. When the pulp is removed from a tooth, taking with it the odontoblasts, we know that the dentine undergoes degenerative changes which involve, among other things, increase in brittleness. This would seem to be attributable to the degeneration of the organic framework of a matrix no longer nourished by the odontoblasts.

Formation of Enamel. While the dentine is being laid down by the cells of the odontoblast layer, the enamel cap of the tooth is being formed by the ameloblast layer of the enamel organ. As was the case with the odontoblasts, the active cells of the ameloblast layer are columnar in shape and their nuclei, too, lie in the ends of the cells toward the source of supplies, in this case the small vessels in the adjacent mesenchyme (Fig. 183). The amount of organic material laid down as the framework of enamel is much less than is the case with either bone or dentine, and it is therefore more difficult to make out its precise character and arrangement. It is, nevertheless, possible to see in decalcified sections, delicate fibrous strands projecting from the tips of the ameloblasts into the areas of newly formed enamel (Fig. 183). It seems probable that these strands {Tomes processes) are in some way involved in the formation of the organic matrix of enamel. The problem of tracing the relations of Tomes’ processes to the organic framework of enamel is greatly complicated by the fact that where the ameloblasts have deposited calcium compounds the calcium has rendered the organic part of the matrix so avid in its affinity for stains that it is not possible to discern fine structural details because of the very density of the resulting coloration (Fig. 183). This reaction of the tissue to stains persists even after the inorganic calcium compounds have been removed by decalcification, indicating that the organic framework itself has been chemically altered by the calcium deposited in it.

THE DEVELOPMENT OF THE TEETH

311

In spite -of these difficulties in getting at the exact nature and arrangement of the organic matrix of enamel, it is quite possible to see the genesis of its fundamental prismatic structure. Each amcloblasl builds up beneath itself a minute rod or prism of calcareous material. These prisms are placed with their long axes approximately at right angles to the dento-enamel junction. Collectively these enamel prisms form an exceedingly hard cap over the crown of the tooth which in its structural arrangement suggests a paving of polygonal bricks laid on end. There is sufficient difference in the rate at which the different

growth lines

in enamel

pulp chamber

growth lines in dentine

root canal

cementum

oral epithelium

osteolilasts

of periosteum of alveolus

connective tissue ftbers

cementoblasts ( from dental sac)

blood vessels and nerves to pulp

Fig. 184. Schematic diagram showing the topography of a tooth and its relations to the bone of the jaw. The numbered zones indicate empirically the sequence of deposition of the dentine and enamel. The so-called growth lines in the dentine and enamel follow the general contours indicated by the dotted lines in the figure but arc much more numerous.

312

DEVELOPMENT OF FACE, JAWS AND TEETH

ameloblasts work so that in actively growing enamel the surface is jagged and irregular due to the varying extent to ^<^hich the different prismatic elements have been calcified (Fig. 183).

Both enamel formation and dentine formation begin at the tip of the crown and progress toward the root of the tooth (Figs. 182 and 184). But the entire crown is well formed before the root is much more than begun. The progressive increase in the length of the root is an important factor in the eruption of the tooth, for as the root increases in length the previously formed crown must move closer to the surface of the gum. Even when the crown of the tooth begins to erupt the root is still incomplete, and it does not acquire its full length until the crown has entirely emerged.

The Formation of Cementum. The so-called cementum of the tooth is virtually a bone encrustation of its root. No cementum is formed until the tooth has acquired nearly its full growth and its definitive position in the jaw. But the first indications of specialization in the tissue destined to give rise to it can be seen long before the cementum itself appears.

Outside the entire tooth germ, between it and the developing bone of the jaw, there occurs a definite concentration of mesenchyme. The concentration becomes evident first at the base of the dental papilla and extends thence crownwards about the developing tooth, which it eventually completely surrounds.

This mesenchymal investment is known as the dental sac (Fig. 182). In the eruption of the tooth the portion of the dental sac over the crown is destroyed, but the deeper portion of the sac persists and becomes closely applied to the growing root. At about the time the tooth has acquired its final position in the jaw, the cells of the dental sac begin to form the cementum. Histologically and chemically cementum is practically identical with subperiosteal bone. When we consider the manner of origin of the dental sac and of the periosteum of the bone socket (alveolar socket) in which the root of the tooth lies, and see how they arise side by side from the same sort of tissue, this seems biit natural. The dental sac is essentially a layer of periosteal tissue facing the root of the tooth and back to back with the periosteal tissue of the alveolar socket (Fig. 182).

The Attachment of Tooth in the Jaw. The attachment of the tooth in its socket is brought about by the development, between the dental sac and the periosteum of the tooth socket, of an exceedingly tough fibrous connective tissue. As the periosteum of the alveolus

THE DEVELOPMENT OF THE TEETH

313

adds new lamellae of bone to the jaw on the one side, and the dental sac adds lamellae of cementum to the root of the tooth on the other, the fibers of this connective tissue are caught in the new lamellae. Thus the tooth comes to be supported by fibers which are literally calcified into the cementum of the tooth at one end and into the bone of the jaw at the other (Fig. 184). The mechanism involved is precisely the same as that which occurs in the burying of tendon fibers in a growing bone, where the buried ends of the fibers are known as the penetrating fibers of Sharpey.

Replacement of Deciduous Teeth by Permanent Teeth. The

replacement of the temporary or “milk” (deciduous) dentition by the permanent teeth is a process which varies in detail for each tooth. The general course of events is, however, essentially similar in all cases. The enamel organ of the permanent tooth arises from the dental ledge near the point of origin of the corresponding deciduous tooth (Fig. 180). With the disappearance of the dental ledge, the permanent tooth germ comes to lie in a depression of the alveolar socket on the lingual side of the developing deciduous tooth (Fig. 185).

When the jaws approach their adult size the hitherto latent primordia of the permanent teeth b<-gin to go through the same histo

Fio. 185. Photomicrograph (X 5) of upper jaw of 160 mm. pig embryo showing the milk cuspids just breaking through the gum.

314

DEVELOPMENT OF FACE, JAWS AND TEETH

Fig. 186. Photomicrograph (X 6) of section through the jaw of a puppy showing a deciduous tooth nearly ready to drop out and the developing permanent tooth deeply embedded in the jaw below it. The space about the crown of the permanent tooth was occupied in the living condition by enamel. Fully formed enamel, being approximately 97 per cent inorganic in composition, is almost completely destroyed by the decalcification with acids which must be carried out before such material can be sectioned. (From a preparation loaned by Dr* S. W. Chase.)

THE DEVELOPMENT OF THE TEETH

315

genetic changes we have already traced in the case of the temporary teeth. As the permanent tooth increases in size, the root of the deciduous tooth is resorbed and the permanent tooth comes to lie underneath its remaining portion (Fig. 186). Eventually nearly the entire root of the deciduous tooth- is destroyed and its loosened crown drops out, making way for the eruption of the corresponding permanent tooth.

BiLlio grapky

Although this docs not purport to be a complete bibliography on the development of the pig, I have tried to make it comprehensive. At least one reference has been included on every phase of the subject concerning which I could find published information. Under each of the main subject headings some of the articles referred to have extensive bibliographies of the literature in their special field. But, with the exception of a few outstanding contributions, no papers have been included which are merely of historical interest. For such articles reference should be made to the exhaustive bibliographies compiled by Minot (1893) and by Keibel (1897). Furthermore, the list is largely restricted to contributions based directly on pig embryos. Exception to this rule has been made in favor of a few general articles which are of especial assistance in acquiring a perspective on some phase of the subject. Also, a number of articles based on other forms have been included when no work appeared to have been done on corresponding phases of development in the pig. It is hoped that such a list of selected references will furnish a starting point for following up any desired line of inquiry without involving one in a discouraging multiplicity of titles.

Texts and Manuals

Arey^ L. i?., 19^6. Developmental Anatomy. Saunders, Philadelphia, 5th Ed., ix &

616 pp.

Baumgartner, W, J,, 1924, Laboratory Manual of the Foetal Pig, Macmillan, New York, vii & 57 pp.

Boyden, E. A., 1936. A Laboratory Atlas of the 13-mm. Pig Embryo. (Prefaced by younger stages of the chick embryo.) The Wistar Institute Press, Philadelphia, iv & 104 pp.

Hamilton, W. J., Boyd, J. D., and Mossman, H. W., 1945. Human Embryology.

Williams and Wilkins, Baltimore, viii & 366 pp.

Hertwig, O., 1901-07. Handbuch der Vergleichenden und experimentellen Entwicklungslehre der Wirbeltiere. (Edited by Dr. Oskar Hertwig and written by numerous collaborators.) Fischer, Jena.

Huettner, A, F., 1941. Fundamentals of Comparative Embryology of the Vertebrates. Macmillan, New York, xiv & 416 pp,

Jordan, H. E,, and Kindred, J. E., 1948. A Textbook of Embryology. Appleton, New York, 5th Ed., xiv & 613 pp.

317

318

BIBLIOGRAPHY

Keihel^ F., 1897. Normentafeln zur Entwicklungsgeschichte der Wirbelthiere. I. Des Schweines. Fischer, Jena, 114 S.

Martin^ P., 1912. Lehrbuch der Anatomic der Haustiere. ^chickhard & Ebner, Stuttgart. (Bd. 1, Allgemeine und vergleichende Anatomic mit Entwicklungsgeschichte, xii & 811 S.)

Minot ^ C, S., 1893. A Bibliography of Vertebrate Embryology. Memoirs, Boston Soc. Nat. History, Vol. 4, pp. 487-614.

Mtnot, C, S., 1911. A Laboratory Textbook of Embryology. The Blakiston Company, Philadelphia, 2nd Ed., xii & 402 pp.

Needham^ J'., 1931. Chemical Embryology. Macmillan, New York, xxii & 2021 pp.

Patten^ B. A/., 1929. Early Embryology of the Chick. The Blakiston Company, Philadelphia, 3rd Ed., xiii & 228 pp.

Patten, B. M., 1946. Human Embryology. The Blakiston Company, Philadelphia, XV & 776 pp.

Stssori, S., 1921. The Anatomy of the Domestic Animals. Saunders, Philadelphia, 2nd Ed., 930 pp.

Wetss, P.y 1939. Principles of Development. A Text in Experimental Embryology. Holt, New York, xix & 601 pp.

IVieman, H. L., 1930. An Introduction to Vertebrate Embryology. McGraw-Hill, New York, xi & 411 pp,

Windle, W, F., 1940. Physiology of the Fetus. Saunders, Philadelphia, xiii & 249 pp.

Zeitzschmann, 0,, 1923-24. Lehrbuch dcr Entwicklungsgeschichte der Haustiere. R. Schoetz, Berlin, 542 S,

General Articles and Articles of Significance for the Interpretation of Developmental Processes

Alexander, J., 1944. The Gene — A Structure of Colloidal Dimensions. Chapt. 37, pp. 808-819, in “Colloid Chemistry,” Vol. V, edited by Jerome Alexander, Reinhold Publishing Corp., New York.

Allen, W. F., 1918. Advantages of sagittal sections of pig embryos for a medical embryology course. Anat. Rec., Vol. 14, pp. 183-191.

Barth, L. G., 1944. Colloid Chemistry in Embryonic Development. Chapt. 39, pp. 851-859, in “Colloid Chemistry,” Vol. V, edited by Jerome Alexander, Reinhold Publishing Corp., New York.

Chambers, R., 1944. Some Physical Properties of Protoplasm. Chapt. 41, pp. 864-875, in “Colloid Chemistry,” Vol. V, edited by Jerome Alexander, Reinhold Publishing Corp., New York.

Conklin, E, G., 1914. The cellular basis of heredity and development. Pop. Sci. Monthly, Vol. 85, pp. 105-133. '

Hartman, C. G., 1 931 . Development of the egg as seen by the physiologist. Sci. Monthly, Vol, 33, pp, 17-28.

Medley, 0. F., 1926. Quantitative study of growth of certain organs in pig fetus. Bull. Med. Coll. Va., Vol. 23, pp. 19-36.

Holtfreter, J., 1947. Changes of structure and the kinetics of differentiating embryonic cells. Jour. Morph., Vol. 80, pp. 57-92.

Holtfreter, J., 1947. Observations on the migration, aggregation and phagocytosis of embryonic cells. Jour. Morph., Vol. 80, pp. 93-111.

THE SEX ORGANS AND GAMETOGENESIS

319

Kingsbury, B. F,, 1926. On the so-called law of anteroposterior development. Anat. Rec., Vol. 33, pp. 73-87.

Lewis, W, H., 1947. Mechanics of invagination. Anat. Rec., Vol. 97, pp. 139-156.

Spemann, H., 1927. Organizers in animal development. Proc. Roy. Soc. London, Ser. B, Vol. 102, pp. 177-187.

Spemann, H., 1938. Embryonic Development and Induction. Yale Univ. Press, New Haven, xii & 401 pp.

The Sex Organs and Gametogenesis

Allen, E., 1923. Ovogenesis during sexual maturity. Am. Jour. Anat., Vol. 31, pp. 439-481.

Allen, E., Kountz, IV. B., and Francis, B. F., 1925. Selective elimination of ova in the adult ovary. Am. Jour. Anat., Vol. 34, pp. 445-468.

Bascom, K. F., 1925. Quantitative studies of the testis. I. Some observations on the cryptorchid testes of sheep and swine. Anat. Rec., Vol. 30, pp. 225-241.

Bascom, K. F., and Ouerud, H. L., 1925. Quantitative studies of the testicle. II. Pattern and total tubule length in the testicles of certain common mammals. Anat. Rec., Vol. 31, pp. 159-169.

Blandau, R. J., 1945. The first maturation division of the rat ovum. Anat. Rec., Vol. 92, pp. 449-457.

Corner, G. W., 1917. Maturation of the ovum in swine. Anat. Rec., Vol. 13, pp. 109 112 .

Comer, G. IV., 1919. On the origin of the corpus luteum of the sow from both granulosa and theca interna. Am. Jour. Anat., Vol. 26, pp. 117-183.

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Hargitt, G. T., 1925-30, The formation of the sex glands and germ cells of mammals. Jour. Morph. & Physiol., Vols. 40, 41, 42, 49.

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The Sexual Cycle, Fertilization, Sex Determination

Allen, E., 1926. The ovarian follicular hormone: a study of variation in pig, cow, and human ovaries. Proc. Soc. Exp. Biol. & Med., Vol. 23, pp. 383-387.

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Cleavage, Germ Layer Formation^ and the Structure of Young

Embryos

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Fetal Membranes and the Relations of the Embryos to the Uterus

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THE NERVOUS SYSTEM AND SENSE ORGANS

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The Nervous System and Sense Organs

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Windle, W. F., Fish, M. W., and O Donnell, J, E., 1934. Myelogeny of the cat as related to development of fiber tracts and prenatal behavior patterns. Jour. Comp. Neur., Vol. 59, pp. 139-165.

^ The Circulatory System

Barclay, A. E., Franklin, K. J., and Prichard, M, M. L., 1944. The Foetal Circulation and Cardiovascular System, and the Changes That Ihey Undergo at Birth. Blackwell Scientific Publications, Ltd., Oxford, xvi & 275 pp.

Barcroft, J., 1946. Researches on Pre-natal Life. Blackwell Scientific Publications, Ltd., Oxford, VoL I, xiii & 292 pp.

Barry, A., 1942. The intrinsic pulsation rates of fragment of the embryonic chick heart. Jour. Exp. Zool., Vol. 91, pp. 119-130.

Begg, A. S., 1920. Absence of the vena cava inferior in a 12-mm. pig embryo, associated with the drainage of the portal system into the cardinal system. Am. Jour. Anat., Vol. 27, pp. 395-403.

Boas, J. E. V., 1887. Ueber die Arterienbogen der Wirbelthiere. Morph. Jahrb., Bd. 13, S. 115-118.

Born, G,, 1888. t)bcr die Bildung dcr Klappan, Ostien und ScheidewSnde im SSugetierherzen. Anat. Anz., Bd. 3, S. 606-612,

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Born^ G., 1889. Beitrage zur Entwicklungsgeschichte dcs Saugcthierherzens. Archf. mikx. Anat., Bd. 33, S. 284-377.

Bremer, J. L., 1902. I. The origin of the pulmonary arteries in ntammals. Am. Jour. Anat., Vol. I, pp. 137-144.

Bremer, J, L., 1909. II. On the origin of the pulmonary arteries in mammals. Anat. Rec., Vol. 3, pp. 334-340.

Butler, E. G., 1927. The relative r61e played by the embryonic veins in the development of the mammalian vena cava posterior. Am. Jour. Anat., Vol. 39, pp. 267-353.

Congdon, E, D., and Wang, H. W , 1926. The mechanical processes concerned in the formation of the differing tvpes of aortic arches of the chick and the pig and in the divergent early development of their pulmonary arches. Am. Jour. Anat., Vol. 37, pp. 499-520.

Davh, D. M., 1910. Studies on the chief veins in early pig embryos and the origin of the vena cava inferior. Am. Jour. Anal., Vol. 10. pp. 461-472.

Doan, C. A., Cunningham, R. S., and Sabin, F R., 1925. Experimental studies on the origin and maturation of avian and mammalian red blood-cells. Carnegie Inst., Contrib. to EmbryoL, Vol. 16, pp. 163-226.

Emmel, V. E., 1914. Concerning certain cytological characteristics of the erythroblasts in the pig embryo and the origin of non-nuclcated erythrocytes by a process of cytoplasmic constriction. Am. Joui. Anat., V^ol. 16, pp. 127-206.

Evans, H. M., 1909. On the development of the aortae, cardinal and umbilical veins and other blood-vessels of vertebrate embryos from capillaries. Anat. Rec., Vol. 3, pp. 498-518

Flint, J. M., 1903. The angiology, angiogenesis, and organogenesis of the submaxillary gland. Am. Jour. Anat., Vol. 2, pp. 417-444.

Frazer, J. E., 1917. Formation of Pars Membranacea Septi. Jour. Anat. & Physiol., Vol. 51, pp. 19-29.

Goss, C. M., 1935. Double hearts produced experimentally in rat embryos. Jour. Exp. Zool., Vol. 72, pp. 33-49.

Goss, C. M., 1938. The first contractions of the heart in rat embryos. Anat. Rec., Vol. 70, pp. 505-524.

Goss, C. M., 1942. The physiology of the embryonic mammalian heart before circulation. Am. Jour. Physiol., Vol. 137, pp. 146-152.

Gregg, R, E., 1946. An arterial anomaly in the fetal pig. Anal. Rec., Vol. 95, pp. 53-65.

Henser, C. H., 1923. The branchial vessels and their derivatives in the pig. Carnegie Inst., Contrib. to Embryol., Vol. 15, pp. 121-139.

Hill, E. C., 1907. On the gross development and vascularization of the testis. Am. Jour. Anat., Vol. 6, pp. 439-459.

His, W., 1900. Lecithoblast und Angioblast der Wirbeltiere. Abhandl. der Math, phys. Klasse der Konigl. Sach. Gesellsch. d. Wissenschaften, Bd. 26, S. 173-328.

Hochstetter, F., 1906. Die Entwicklung dcs Blutgefasssystcms. Hertwig’s Handbuch, Bd, 3, Teil 2, S. 21-166.

Hofmann, L. v., 1914. Die Entwicklung der Kopfartcricn bei Sus scrofa domesticus. Morph. Jahrb., Bd. 48, S, 645-671.

Hogue, M. J., 1937. Studies of heart muscle in tissue cultures. Anat. Rec., Vol. 67,

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Jordan^ H. E., 1916. The microscopic structure of the yolk-sac of the pig embryo with especial reference to the origin of erythrocytes. Am. Jour. Anat., Vol. 19, pp. 277-303.

Jordan^ H. E., 1919a. The histogenesis of blood-platelets in the yolk-sac of the pig embryo. Anat. Rec., Vol. 15, pp. 391-406.

Jordan^ H. 1919b. The histology of the umbilical cord of the pig, with special reference to the vasculogenic and hemopoietic activity of its extensively vascularized connective tissue. Am. Jour. Anat., Vol. 26, pp. 1-27.

Kellogg. H. B,, 1928. The course of the blood flow through the fetal mammalian heart. Am. Jour. Anat., Vol. 42, pp. 443-465.

Kellogg^ H. B.j 1929. Studies on the fetal circulation of mammals. Am. Jour. Physiol., Vol. 91, pp. 637-648.

Kimball^ P., 1928. A comparative study of the vas subin testinale in the vertebrates. Am. Jour. Anat., Vol. 42, pp, 371-398.

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Lewis, F. T., 1902. The development of the vena cava inferior. Am. Jour. Anat., Vol. 1, pp. 229-244.

Lewis, F. T., 1906. The fifth and sixth aortic arches and the related pharyngeal pouches in the rabbit and pig. Anat. Anz., Bd. 28, S. 506-513.

Lockwood, C. B., 1888. The early development of the pericardium, diaphragm and great veins, Phil. Trans Roy. Soc. London, Ser. B, Vol. 179, pp. 365-384.

McClendon, J. F., 1913. Preparation of material for histology and embryology, with an appendix on the arteries and veins in a thirty-millimeter pig embryo. Anat. Rec., Vol. 7, pp. 51-61,

McClure, C, F, W., 1921. The endothelial problem. Anat. Rec., Vol. 22, pp. 219-237.

McClure, C. F. W., and Huntington, G. S., 1929. The mammalian vena cava posterior. Am. Anat. Mem., No. 15, 56 pp. and 46 plates.

Minot, C. S., 1898. On the veins of the Wolffian bodies in the pig. Proc. Boston Soc. Nat. Histi, Vol. 28, pp. 265-274.

Morrill, C. V., 1916. On the development of the atrial septum and the valvular apparatus in the right atrium of the pig embryo with a note on the fenestration on the anterior cardinal veins. Am. Jour. Anat., VoL 20, pp. 351-374.

Odgers, P, N. B., 1938. The development of the pars membranacea septi in the human heart. Jour. Anat., Vol. 72, pp. 247-259.

Paff, G, H., 1936. Transplantation of sino-atrium to conus in the embryonic heart in vitro. Am. Jour. Physiol., Vol. 117, pp. 313-317.

Parker, G. H., and Togier, C. H., 1898. The thoracic derivatives of the posterior cardinal veins of swine. Bull. Museum of Comp. Zool., Harvard, Vol. 31, pp. 133-144.

Patten, B, M., 1930. The changes in circulation following birth. Am. Heart Journal, Vol. 6, pp. 192-205.

Patten, B. M., 1931. The closure of the foramen ovale. Am. Jour. Anat., Vol. 48, pp. 19-44.

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Patten^ B, M., and Kramer, T, C., 1933. The initiation of contracfion in the embryonic chick heart. Am. Jour. Anat., Vol. 53, pp. 349-375.

Patten, B. M., Sommerjield, W. A., and Paff, G. H., 1929. Functional limitations of the foramen ovale in the human foetal heart. Anat. Rec., Vol. 44, pp. 165-178.

Pohlman, A. G., 1909. The course of the blood through the heart of the fetal mammal, with a note on the reptilian and amphibian circulations. Anat. Rec., Vol. 3. pp. 75-109.

Rathke, H., 1843. Ueber die Entwicklung der Arterien welche bei den Saugethieren von dem Bogen der Aorta ausgehen. Arch. f. Anat, u. Physiol., Jg. 1843, S. 276-302.

Reagan, F., 1912. The fifth aortic arch of mammalian embryos and the nature of the last pharyngeal evagination. Am. Jour. Anat., Vol. 12, pp. 493-514.

Reagan, F. P., 1917. Experimental studies on the origin of vascular endothelium and of erythrocytes. Am. Jour. Anat., Vol. 21, pp. 39-175.

Reagan, F. P., 1919. On the later development of the azygos veins of swine. Anat. Rec., Vol. 17, pp. 111-126.

Reagan, F. P., 1927. The supposed homology of vena azygos and vena cava inferior considered in the light of new facts concerning their development. Anat. Rec., Vol. 35, pp. 129-148.

Reagan, F, P., 1929. A century of study upon the development of the eutherian vena cava inferior. The Quarterly Review of Biology, Vol. 4, pp. 179-212.

Reinke, E. E., 1910. Note on the presence of the fifth aortic arch in a 6-mm. pig embryo. Anat. Rec., Vol. 4, pp. 453-459.

Robinson, A., 1903. The early stages of the development of the pericardium. Jour. Anat. & Physiol., Vol. 37, pp. 1-17.

Sabin, F. R., 1915. On the fate of the posterior cardinal veins and their relation to the development of the vena cava and azygos in pig embryos. Carnegie Inst., Contrib. to Embryol,, Vol. 3, pp. 5-32.

Sabin, F. R., 1917. Origin and development of the primitive vessels of the chick and the pig. Carnegie Inst., Contrib. to Embryol., Vol. 6, pp. 61-124.

Schafer, 7* P-, 1914. The behavior of elastic tissue in the post-fetal occlusion and obliteration of the ductus arteriosus (Botalli) in Sus scrofa. Jour. Exp. Med., Vol. 19, pp. 129-143.

Shaner, R. F., 1928. The development of the muscular architecture of the ventricles of the pig’s heart, with a review of the adult heart and a note on two abnormal mammalian hearts. Anat. Rec., Vol. 39, pp. 1-36.

Shaner, R. F., 1929. The development of the atrioventricular node, bundle of His, and sino-atrial node in the calf, with a description of a third embryonic nodelike structure. Anat. Rec., Vol. 44, pp. 85-99.

Smith, H. W., 1909. On the development of the superficial veins of the body wall in the pig. Am. Jour. Anat., Vol. 9, pp. 439-462.

Stienon, L., 1926. Recherches sur Foriginc du noeud sinusal dans le coeur dcs mammif^res. Archives de Biologic, T. 36, pp. 523-539.

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Thienes, C. //., 1925. Venous system associated with the liver of a 6-mm. pig embryo. Anat. Rec., Vol. 31, pp. 149-158.

Whitehead, W. H,, 1942. A working model of the crossing caval blood streams in the fetal right atrium. Anat. Rec., Vol. 82, pp. 277-280.

Windle, W, F., 1940. Circulation of blood through the fetal heart and lungs and changes occurring with respiration at birth. Quart. Bull., Northwestern Univ. Med. School, Vol. 14, pp. 31-36.

Witte, L., 1919. Histogenesis of the heart muscle of the pig in relation to the appearance and development of the intercalated discs. Am. Jour. Anat., Vol. 25, pp. 333-347.

Woollard, H. L., 1922. The development of the principal arterial stems in the forelimb of the pig. Carnegie Inst., Contrib. to Embryol., Vol. 14, pp. 139-154.

Toshida, T., 1932. On the development of the heart primordia. II. Observations upon the development of the interatrial septum of the pig. Okayama-Igakkai-Zasshi, Vol. 44, pp. 438-460.

Young, A, H., and Robinson, A., 1898. The development and morphology of the vascular system in mammals. The posterior end of the aortae and the iliac arteries. Jour. Anat. & Physiol., Vol. 32, pp. 605-607.

Lymphatic Vessels and Organs

Badertscher, J. A., 1915. The development of the thymus in the pig. I. Morphogenesis. Am. Jour. Anat., Vol. 17, pp. 317-338. II. Histogenesis. Am. Jour. Anat., Vol. 17, pp. 437-494.

Battjer, W. A., 1908. The origin of the mesenteric sac and thoracic duct in the embryo pig^ Am. Jour. Anat., Vol. 8, pp. 303-310.

Bell, E. T., 1905. The development of the thymus. Am. Jour. Anat., Vol. 5, pp. 29-61.

Cash, J. R., 1917. On the development of the lymphatics in the heart of the embry^o pig. Anat. Rec., Vol. 13, pp. 451-464.

Cash, J, R., 1921. On the development of the lymphatics in the stomach of the embryo pig. Carnegie Inst., Contrib. to Embryol., Vol. 13, pp. 1-15.

Clark, A. H., 1912. On the fate of the jugular lymph sacs and the development of the lymph clyannels in the neck of the pig. Am. Jour. Anat., Vol. 14, pp. 47-62.

Cunningham, R, S., 1916. On the development of the lymphatics of the lung in the embryo pig. Carnegie Inst., Contrib. to Embryol., Vol. 4, pp. 45-68.

Fischelis, P., 1885. Beitrage zur Kenntnis der Entwiqklungsgeschichte der Gl. thyreoidea und Gl. thymus. Arch, f. mikr. Anat., Bd, 25, S. 405-440.

Fox, H., 1908. The pharyngeal pouches and their derivatives in the mammalia. Am. Jour. Anat., Vol. 8, pp. 187-250.

Heuer, G. J,, 1909. The development of the lymphatics in the small intestine of the pig. Am, Jour, Anat., Vol. 9, pp. 93-118.

Holyoke, E, A., 1936. The role of the primitive mesothelium in the development of the mammalian spleen. Anat. Rec., Vol. 65, pp. 333-349.

Huntington, G, S., 1910a. The phylogenetic relations of the lymphatic and blood vascular systems in the vertebrates. Anat. Rec,, Vol, 4, pp. 1-14,

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Reichert, F. L,, 1921. On the fate of the primary lymph-sacs in the abdominal region of the pig, and the development of the lymph-channels in the abdominal and pelvic regions. Carnegie Iirst., Contrib. to Embryol., Vol 13, pp. 17-39.

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Sabin, F, R,, 1904. On the development of the superficial lymphatics in the skin of the pig. Am. Jour. Anat., Vol. 3, pp. 183-195.

Sabin, F. R., 1905. The development of the lymphatic nodes in the pig and their relation to the lymph hearts. Am. Jour. Anat., Vol. 4, pp. 355-389.

Sabin, F. R., 1912. On the origin of the abdominal lymphatics m mammals frc:)m the vena cava and the renal veins. Anat. Rec., Vol. 6, pp. 335-342.

Sabin, F. /?., 1916. The origin and development of the Ivmphatic system. Johns Hopkins Hosp. Rep., Vol. 17, pp. 347-440.

Theil, G, A., and Downey, //., 1921. The development of the mammalian spleen, with special reference to its hematopoietic activity. Am. Jour. Anat., Vol. 28, pp. 279-339.

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The Digestive and Respiratory Systems, and the Body Cavities

and Mesenteries

Boyden, E. A., 1926. The accessory gall bladder. An embryological and comparative study of aberrant biliary vesicles occurring in man and the domestic animals. Am. Jour. Anat., Vol. 38, pp. 177-231.

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Corner, G. W., 1914. The structural unit and growth of the pancreas of the pig. Am. Jour. Anat., Vol. 16, pp. 207-236.

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Flint, J. M., 1902. The development of the reticulated basement membranes in the submaxillary gland. Am. Jour. Anat., Vol. 2, pp. 1-11.

Flint, J, M., 1903. The angiology, angiogenesis, and organogenesis of the submaxillary gland. Am. Jour. Anat., Vol. 2, pp. 417-444.

Flint, J. M., 1906. The development of the lungs. Am. Jour. Anat., Vol. 6, pp. 1-138. Horn, A. IT., and Baldwin, K. W., 1941. A histological study of the development of the lung with particular reference to the nature of alveoli. Anat. Rec., Vol. 81, pf). 363-379.

Harnrnar, G. A , 1893. Einige Plattenmodelle zur Beleuchtung der friiheren embryonalen Leberentwic kelung. Arch. f. Anat. u. Phvs., Anat. Abt., f. 1893, S. 123-156.

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}ler::Jeld, P., 1889. Ueber das Jacobson'sche Organ des Menschen und der Saugethiere. Zoolog. Jahrb. (Abt. f. Anat. u. Ontogenie), Bd. 3, S. 551-574.

Huber, G. C., 1912. On the relation of the chorda dorsalis to the anlagc of the pharyngeal bursa or mc'.dian pharyngeal recess. Anat. Rec., Vol. 6, pp. 373-404. Johnson, F, P., 1919. The development of the lobule of the pig’s liver. Am. Jour. Anat., Vol. 25, pp. 299-331.

Lewis, F. T., 1911. 7Te bi-lobed form of the ventral pancreas in mammals. Am. Jour. Anat., Vol. 12, pp. 389-400.

Lewis, F. T., and Thyng, F. IT., 1908. The regular occurrence of intestinal diverticula in embryos of the pig, rabbit and man. Am. Jour. Anat., Vol. 7, pp. 505-519. Linehack, P, E., 1916. The development of tlie spiral coil in the large intestine of the pig. Am. ijour. Anat., Vol. 20, pp. 483-503.

Mall, F. jP., 1891. Development of the lesser peritoneal cavity in birds and mammals. Jour, Morph,, Vol. 5, pp. 165-179.

Mall, F. P., 1906. A study of the structural unit of the liver. Am. Jour. Anat., Vol, 5, pp. 227-308.

Max, C., 1931. Das Wachstum der Leberzellen und die Entwicklung der Leberlappchen beim Schweine. Anat. Anz., Bd. 72, S. 219-227.

Ravn, E., 1889. Ueber die Bildung der Scheidewand zwishen Brust- und Bauchhdhle in Saugetier-embryonen. Arch. f. Anat. u. Phys., Anat. Abt., S. 123-154.

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Whitehead, W. H., Windle, W. F , and Becker, R, F,, 1942. Changes in lung structure during aspiration of amniotic fluid and during air-breathing at birth. Anal. Rec., Vol. 83, pp. 255-265.

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The Urogenital System

Allen, B. M,, 1904. The embryonic development of the ovary and testis of the mammals. Am. Jour. Anat., Vol. 3, pp. 89-154.

Angle, E, J,, 1918. Development of the Wolffian body in bus scrofa domesticus. Trans. Am. Micr. Soc., Vol. 37, pp. 215-238.

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Bascom, K. F,, and Osterud, H. L., 1927. Quantitative studies of the testis. III. A numerical treatment of the development of the pig testis. Anat. Rec., Vol. 37, pp. 63-82.

Bremer, J, L., 1916. The interrelations of the mesonephros, kidney, and placenta in different classes of animals. Am. Jour. Anat., Vol. 19, pp. 179-209.

Brody, H,, and Bailey, P. L., Jr,, 1939. Unilateral renal agenesia in a fetal pig. Anat. Rec., Vol. 74, pp. 159-163.

Corner, G. W,, 1920. A case of true lateral hermaphroditism in a pig with functional ovary. Carnegie Inst., Contrib. to Embryo!., Vol. 11, pp. 137-142.

Felix, W., und Buhler, A., 1906. Die Entwicklung der Harn- und Geschlechts organe.

Hertwig’s Handbuch, Bd. 3, Teil I, K. II.

Flexner, L. B,, and Gersh, /., 1937. The correlation of oxygen consumption, function and structure in the developing rnetanephros of the pig. Carnegie Inst., Contrib. to Embryo!., Vol. 26, pp. 121-127.

Gersh, 1937. The correlation of strucmre and function in the developing mesonephros and rnetanephros. Carnegie Inst,, Contrib. to Embryo!., Vol. 26, pp. 33-58. Gruenwald, P,, 1942. The development of the sex cords in the gonads of man and mammals. Am. Jour. Anat., Vol. 70, pp. 359-397.

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THE DUCTLESS GI.ANDS

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Hennebergj B.y 1926. Beitrag zur ontogcnetischen Entwicklung des Scrotums und der Labia maiora. Zeitschr. f. Anat. u. Entwg., Bd. 81, S. 198-219.

Hilly E. C.y 1905. On the first appearance of the renal artery and the relative development of kidneys and Wolffian bodies in pig embryos. Bull. Johns Hopkins Hosp., Vol. 16, pp. 60-64.

Hilly E. C,y 1906. On the gross development and vascularization of the testis. Am. Jour. Anat., Vol. 6, pp. 439-459.

Huber y G. C., 1905. On the development and shape of uriniferous tubules of certain of the higher mammals. Am. Jour. Anat., Supplement to Vol. 4, pp. 1-98. Kambmeiery O, F.y 1926. The rnetanephros or so-called permanent kidney in part provisional and vestigial. Anat. Rec., Vol. 33, pp. 115-120.

King^burjiy B. F.y 1913. The morphogenesis of the mammalian ovary: Felis domestica. Am. Jour. Anat., Vol. 15, pp. 345-387.

Kitaharay T., 19-23. Uber die Entstehung der Zwischenzellen der Keimdru.sen des Menschen und der Saugetiere und fiber deren physiologische Bedeutung. Arch, f. Entwcklngsmechn. d. Organ., Bd. 52, S. 550-615. *

Klaafsch, //., 1890. Ueber den Descensus testiculorum. Morph Jahrb., Bd. 16, S. 587-646.

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Lockwoody C. B.y 1888. Development and transition of the testis, normal and abnormal. Jour. Anat. & Physiol., Part I, Vol. 21, pp. 635-664. Part II, Vol. 22, pp. 38-77. Part III, Vol. 22, pp. 461-478. Part IV, Vol. 22, pp. 505-541.

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The Ductless Glands

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CONNECTIVE TISSUES, SKELETAL, AND MUSCULAR SYSTEMS 337

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Connective Tissues, Skeletal, and Muscular Systems

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Teeth, Hair, and Hoofs

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TWINS, DOUBLE MONSTERS, ANOMALIES

339

Bevelander, G., and Johnson^ P. L., 1945. The histochemical localization of alkaline phosphatase in the developing tooth. Jour. Cell. & Comp. Physiol., Vol. 26, pp. 25-33.

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Schmidt, V,, 1925. Studien fiber die Histogencse der Haut und ihrer Anhangsgebilde bei Saugetieren und beim Menschen. I. Die Histogencse des Hufes bei Schweineembryonen. Zeitschr, f. mikr. Anat. Forsch., Bd. 3, S. 500-557.

Schour, /., and Steadman, S. R., 1935. The growth pattern and daily rhythm of the incisor of the rat. Anat. Rec., Vol. 63, pp. 325-333.

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Thoms, H., 1896. Untersuchungen fiber Bau, Wachsthum und Entwicklung des Hufes der Artiodactylen, insbesondere des Sus scrofa. Deutsche Thieraerzliche Wochenschr., Jahrgang. 4, S. 379-383.

Z^itzschmann, 0., 1924. Die Entwicklung des Systems der ausseren Haut. (b) Die Haare. (Schwein.) Lehrbuch der Entwicklungsgcschichte der Haustierc, S. 186-194.

Twins, Double Monsters, Anomalies

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Index

To facilitate the use of this book in connection with otheis in which the terminology may differ somewhat, many synonyms which were not used in the text have been put into the index and cross-referenced to the alternative terms used in this book; for example, Wolffian body, a teim not used in this text, is frequently applied to the mesonephros. It appears m the index thus: Wolffian body (= mesonephros, q.v.).

Both figure and page references are given in the index. The figure references arc preceded by the letter /.

Abdominal pregnancy, 217 Abducens nerve, 169 Accessory nerve, 172 Acoustic ganglion, /92, 117, 169 Acoustico-facialis ganglion ( = early undifferentiated condition of ganglia of 7th and 8th cranial nerves), 169 Action system, 141

Adrenal, /1 00, /106, /1 27, /1 28, /1 38, 223 After-birth, 105 Alae of nose, 296 Alar plate of neural tube, 1 57 Allantois, circulation of, /45,/51, 99 formation of,/30,/37, 99 function of, 106 relations of,/49,/55, 103 Alveolar periosteum, 312 Ameloblasts,/179-183, 305, 310 Amnion, formation of,/25,/37,/50, 97 function ofi 96 relations of,/49, 97 Amniotes, 96 Amniotic folds, 97 Ampulla of ductus deferens, /3, 8 Anal plate ( = cloacal plate, q.v.) Anamniotes, 96 Angioblast, 87 footnote Animad pole, 37

Anterior intestinal portal, /37, 74 Anterior neuropore, /29, 71 Anus,/118,/132, 210, 225 Aorta, see arteries Aortic arches, sec arteries Aortic bulb, 256 Aortic chromaffin body, 223 Appendage buds, /3 1-34, 65, 109

Appendix, of epididymis, /1 24, 213 of testis, /1 24, 217 Appositional growth, 278 Aqueduct of Sylvius, 158 Archenteron, 43 Areola, 105

Arterial circle (of Willis), 131 Arteries, allantoic, /45,/51, 89, 132, 240 aorta, dorsal, /67, /1 33-1 37, 88, 131, 235, 240

aoita, ventral, /45, /1 33, 88, 235 aortic arches, /45, /1 33-1 37, 88, 129,

233

basilar, /66, /67, /133, /137, 131, 238 brarhio-cephalic,/133, 234 carotid, common, /1 33, /1 37, 234 carotid, external, /67, /1 33, /1 37, 130,

234

carotid, internal, /66, /133, /137, 130, 234, 238 caudal, 240

cervical, intersegmental,/66,/133,/l37, 130, 235

coeIiac,/67,/lll, 132, 240 ductus arteriosus /1 33, /ISO, 235, 262, 268

hypogastric, 240, 270 iliacs,/66, /150, 240 innominate, 234 internal mammary, 238 interscgmcntal,/67,/133, 130, 235 mesenteric, ant., /67, /1 11, 132, 238 mesenteric, post»,/lll, 238 omphalomesenteric, /45, 89, 131, 238 pulmonary, /67, /1 33-1 37, 130, 234, 267

341

342

INDEX

Arteries — {Continued)

renal, /1 27, /1 28, 240 speimatic, /1 27-1 30

subclavian, /67, /133-135, 131, 234, 235

umbilical (allantoic), /66, /1 50, 89, 132, 240

vertebral,/66,/67,/137, 131, 237 vitelline, /45, 89, 132 Arytenoid process of larynx, /1 38 Astrocytes, 150 Atresia of ovarian follicles, 20 Atrio-ventricular canal, 126, 256 Atrium, 126, 254

Auditory, ganglion, see acoustic nerve, 1 69 vesicle, /36,/61, 117, 169

Basal plate of neural tube,/91, 157 Belly-stalk, /49, 97 Bicornate uterus, 216 Bile duct, common, 185 Bladder (urinary), /118, /124, /125, /130, 209

Blastocoele, j\S, 41 Blastocyst, /1 7, 41

elongation of, /1 8, 45 riastodermic vesicle ( == blastocyst, q.v.) Blastodisc ( — embryonic disc, q.v.) Blastorneie, 38 Blastula, 41

Blood cells, formation of,/48,/152, 90, 251 Blood islands, /48, 89, 251 Blood vessels, formation of, /48, 87 see also arteries and veins Body axis, 60 Body cavity, see coelom Body folds, /38, 72 Body-stalk, sec belly-stalk Bone, cancellous, 272 cells, /1 51, /1 52, 275 compact, 272 endochondral, 272 histogenesis of, 271 intramembranous, 272 lacuna, 275 lamellae, /1 51, 275 marrow, /1 52, 251 matrix, /1 51, 273 trabeculae, /1 51, /1 53, 274 Bone, formation of,

compact from cancellous, 281

Bone — '{Continued)

endochondral, /1 55, 276 flat, /1 57, 282 '

intramem branous, /1 5 1 , /1 53, 272 long, /1 58, 283

primary cancellous, /1 51, /153, 272, 281

Bowman’s capsule, /1 16, 203 Brachial plexus, 116 Brain, formation of, /36, 69 neuromeric structure of, 69 regional differentiation of,/87, 1 S4 ventricles of, /88, 156, 160 3-vesicle stage, /36, 70 5-vesicle stage, /60, 110 Branchial arches (= gill arches, q.v.)

Bridge of nose, 296

Broad ligaments of uterus, 222

Bronchi, 189

Bulbo-urethral gland, /3, /1 24, 9, 213

Clalcification

of bone, 274 of teeth, 309

Calyces of renal pelvis, /1 19 Canal, atrio-ventncular, 126 Haversian, /1 56, 282 inguinal, /1 29, 222 of Gartner, 217 pleural,/! 10 pleuro- peritoneal, 195 semicircular, 169 Canalicuii, /152 Cancellous bone, /1 53, 276 Capsule, glomerular, /1 21, 203 of Bowman, /1 21 , 203 of cartilage cells, 278 Cardiac loop, /1 42, 125, 254 Cardinal vessels, see veins “Cartilage bone,” 272 Cartilage, erosion, /1 55, 280 formation, /1 54, 277 matrix, 278 Caval plica, /1 40, 245 Cecum, /102, 122, 182 Cementoblasts, /1 84 Cemcntum,/184, 312 Central canal of spinal cord,/86, 151 Centrum, see vertebrae Cephalic region, differentiation of, 61 mesoderm of, 1 91

INDEX

343

Cephalic region — (Continued) precocity of, 54 Cerebellar peduncles, 157 Cerebellum, /80,/87, 157 Cerebral aqueduct, 158 Cerebral cortex, 145, 162 Cerebral ganglia, see ganglia, cranial Cerebral hemispheres, /87, 162 Cerebral peduncles, /1 00, 158 Cerebro-spinal paths, 142 Cervical flexure, 66 Cervical sinus, /32, /1 69, 109 Cervix of uterus, 216 Choanae, of nose, 296 Chondrin, 278 Chondrogenesis, 276 Chondrogenctic layer, 278 Chorda dorsalis ( = notochord, q.v.)

Chorion, /55-57, 103 Chorionic vesicle, /54, 103 Chorionic villi, /57 Choroid fissure, of eye,/39, 117 Choroid plexus, anterior (of 3rd ventricle), /106, 158, 162

lateral (of 1st and 2nd ventricles), /1 00.

162

posterior (of 4th ventricle), /65, /99, /1 38, 156

Chromaffin tissue, 223 Chromosomes, sex, 23 species number of, 21 Circle of Willis, /1 33, 131 Circulation, changes in at birth, 268 early embryonic, /45,/51, 92 hepatic portal, 241 interpreta^tion of embryonic, 227 placental,/45,/51,/55, 93, 263 pulmonary, 262, 267 vitelline, /45, /1 41, 93, 249 Circulatory arcs, 92 Cleavage, /1 2, /1 3, /1 4, 37 Cleavage cavity, see blastococle aitoris,/132, 225 Cloaca, /65, /1 18, 120, 209 Cloacal plate (membrane), /37, 209 Cochlea, 169 Coelom, /1 09

abdominal, /1 11, 194 diflferentiation of, /1 08, 193 formation of,y20, f22,/108, 51, 120, 189 intra- and extra-embryonic, 52, 190

Coelom — (Continued)

partitioning of, /1 11-1 13, 194 pericardial, /26, /44, /1 09, /1 10, /111, 53, 87, 195 peritoneal, /1 10, 189 pleural,/! 11, /1 13, 194 thoracic, 194

Colliculi, inferior, suptTior (lobes of corpora quadngemma), /80, /87, 157, 167 Colon (large intestine), /1 02, 182 Columns of spinal cord, /8 6, 154 Commissural ganglion, /92, 172 Components of spinal nerve, 151 Concrescence, /20, 46 Coordinating centers, 145 Copula, /41 Cord, spinal, 71, 115

and reflexes, /80, 142 histogenesis of, /8 1-8 3, 147 white and grey matter of,/86, 151 Cord, umbilical, 250 Corona radiata, 18 Coronary sinus, sec veins Corpora quadrigemma, /87, 157 Corpus albicans, 27 Corpus hacmorrhagicurn, 26 Corpus luteum, formation of,/6, 24 in pregnancy, /1 0, 26 significance of, 33 Corpus striatum, 1 63

Cowper’s gland (= bulbo-urethral gland, q.v.)

Cranial flexure, 66

Cranial ganglia, see ganglia

Cranial nerves, see nerves

Crura cerebri (= cerebral peduncles, q.v.)

Cumulus oophorus, 19

Cutis plate, see dermatome

Cystic duct,/104,/105, 184

Decalcification, 274 Deciduous placenta, 103 Deitcr’s nucleus, /80, 144 Dental ledge, /1 75-1 80, 302 Dental papilla, 307 Dental sac, /1 82, 312 Dentinal fiber /1 83, 310 Dentine, /1 83, 307 Dermatome, /42, 81

Deutoplasm, effect of on cleavage, /1 2, 37 in pig ovum, 39

344

INDEX

Diaphragm, /1 00, /1 12, 194 Diaphragmatic ligament of mesonephros, /1 23, 218

Diaphysis, of long bone, 283 Dicnccphalon, /60, 110, 158 Diestrum, 29

Diocoele ( =« lumen of diencephalon) Dio-mesencephalic boundary, 110 Dio-telcncephalic boundary, 110 Diploe, of bone, 282 Diploid number of chromosomes, 22 Dorsal, aorta, see arteries flexure, 66

mesentery, /1 08, /1 11, 192 mesocardium,/43,/144, 87, 254 nerve roots, see nerves, spinal root ganglia, see ganglia, spinal Duct of, Cuvier ( = common cardinal vein, q.v.)

Santorini, 186 Wirsung, 186

Ductus, arteriosus, /1 33, /1 38, /1 50, 235, 262, 268

choledochus ( = common bile duct, q.v.) deferens, /3, /1 18, /1 24, 9, 213 endolymphaticus, 117 venosus, see veins Duodenum, /1 00, /1 02, 184

Ear, external, /33,/34, 62 internal, 62, 117, 169 middle, 118, 170 Ectoderm, 59, 98

derivatives of,/27 Efferent ductules, 213 Egg nests, 1 5

Ejaculatory duct, /3, /1 24, 9, 213 Embryonic disk, /1 6, /1 9, 45, 60 Enamel, /183, 310 Enamel organ, /1 79-1 82, 303 Enamel prisms, 311

Endocardial cushion of A-V. canal, /39, /147,/148, 126, 256 Endocardial cushion tissue, 256 Endocardial primordia,/43,/44, 85 Endocardium, 85 Endolymphatic duct, 117 Endothelium, origin of vascular, /48, 87 Entoderm, 59

derivatives of, /27 formation of, /1 6, 43

Eparterial bronchus, /1 07 Ep>endymal cells, 150 Ependymal layer of c^d,/81, 147 Epicardium, 85

Epididymis, /3, /1 24, /1 29, 213

Epi-myocardium,/43,/44, 85

Epiphyseal cartilage plates, 284

Epiphyseal ossification centers, 284

Epiphyses of long bones, /1 58, 284

Epiphysis, of diencephalon, /1 06, 110, 158

Epiploic foramen, 181

Epo6phoron,/125, 217

Equation division, 22

Erythroblasts, /1 52

Esophagus, /64,/72, 80, 119, 179

Estrus, 29

Estrus cycle, /9, 29

Eustachian tube, 118, 175

Evolution, 198, 229

Exocoelom, 52

Extra-embryonic coelom, see coelom Extra-embryonic membranes, /49, 94 Eye, 63, 116, 167

Face, development of, /1 68-1 72, 293 Facial nerve, /92, 169 Falciform ligament, /1 1 1 , 193 Fallopian tube (= uterine tube, q.v.) Fasciculi, see columns of spinal cord Fertilization, /1 1, 34 Flexion, 65, 107 Floor plate of neural tube, 156 Fetal membranes, see extra-embryonic membranes

Follicle, ovarian, /6,/7, 17 Foramen, ovale, 260, 267, 268 see also interatrial

Foramen of Monro, /88, /1 38, 160 Foramen of Winslow, 181 Fore-brain, see prosencephalon Fore-gut, /26,/37, 74 Fossa ovalis, 269

Fovea cardiaca (= ant. intestinal portal, q.v.)

Frontal lobe, 163

Frontal process, /1 68-1 72, 293

Froriep’s ganglion, /92, 172

Gall-bladder, /46, /103-105, /1 40, 80, 119, 184

Gametes, /8, 9, 12, 15

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Cite this page: Hill, M.A. (2024, May 7) Embryology Book - Embryology of the Pig. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Embryology_of_the_Pig

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