Difference between revisions of "McMurrich1914 Chapter 2"

From Embryology
(Created page with "{{McMurrich1914 header}} CHAPTER II. THE SEGMENTATION OF THE OVUM AND THE FORMATION OF THE GERM LAYERS. Segmentation. - The union of the male and female pronuclei has...")
Line 330: Line 330:
In the preceding chapter the development of the mammalian ovum has been described up to and including the formation of the three germinal layers. The earlier stages of development there described are practically unknown in the human ovum, but for the stages subsequent to the establishment of the germinal layers human material is available, and it will, therefore, now be convenient to consider the structure of the younger human ova at present known and to trace in them the appearance and development of such structures as the primitive streak, the head process and the gastral mesoderm.
The youngest human ovum at present known is that described by Bryce and Teacher, but, unfortunately, it presents certain features that are evidently abnormal, so that it becomes doubtful how far it may be accepted as representing the typical condition. The trophoblast, which was very thick and clearly differentiated into two layers, enclosed a space whose diameter was about 0.63 mm. and which was largely occupied by a loose syncytial tissue, presumably mesoderm. Toward the center of this was an irregular cavity in which were two vesicles, quite separate from one another and probably together representing the embryo, the smaller one being the amniotic cavity and the larger one the yolk-sac (Fig. 36). The separation of these two structures is apparently an abnormality and it is possible that the cavity in which they lie is, as Bryce and Teacher suggest, an artefact produced by contraction of the syncytial mesoderm during the preservation of the ovum.
If comparison of this ovum with those of other mammals is warranted, it may be likened to that of the bat as shown in Fig. 29,
C, with the difference that the mesoderm that lines the trophoblast in that ovum has become much more voluminous and forms the syncytial mass in which the ovum is supposed to have been imbedded, a condition that may be "represented diagrammatically as in Fig. 38, A.
Somewhat older are the ova described by Peters, Fetzer, Jung and Herzog. The Peters ovum was taken from the uterus of a
Fig. 36.
-From a Reconstruction of the Bryce-Teacher Ovum.  -  (Bryce-Teacher .)
woman who had committed suicide one calendar month after the last menstruation, and it measured about 1 mm. in diameter. The entire inner surface of the trophoblast (Fig. 37, ce) was lined by a layer of mesoderm (cm), which, on the surface furthest away from the uterine cavity, was considerably thicker than elsewhere, forming an area of attachment of the embryo to the wall of the ovum. In the substance of this thickening was the amniotic cavity (am), whose roof was formed by flattened cells, which, at the sides, became continuous with a layer of columnar cells forming the floor of the cavity and constituting the embryonic ectoderm (ec). Immediately 5
below this was a layer of mesoderm (m) which split at the edge of the embryonic disk into two layers, one of which became continuous with the mesodermic thickening and so with the layer of mesoderm lining the interior of the trophoblast, while the other enclosed a sac lined by a layer of endodermal cells and forming the yolk-sac (ys). The total length of the embryo was 0.19 mm., and so far as its ectoderm and mesoderm are concerned it might be described as a
<r \
1 *-5SC§* ^k « m
Fig. 37.  -  Section of Embryo and Adjacent Portion of an Ovum of i mm.
am, Amniotic cavity; ce, chorionic ectoderm; cm, chorionic mesoderm; ec, embryonic
ectoderm; en, endoderm; m, embryonic mesoderm; ys, yolk-sack.  -  (Peters.)
flat disk resting on the surface of the yolk-sac, though it must be understood that the yolk-sac also to a certain extent forms part of the embryo.
This embryo seems to be in an early stage of the primitive streak formation, before the development of the head process. On comparing it with the stage of development represented in Fig. 38, A, it will be seen to present some important advances. The cavity (Fig. 38, B, C) into which the yolk-sac projects is unrepresented in
6 7
Fig. 38, A. How this cavity is formed can only be conjectured, but it seems probable that it arises by the splitting of the layer of cells which lines the interior of the trophoblast in the earlier stage (or perhaps by the vacuolization of the central cells of this layer) and the subsequent accumulation of fluid between the two mesodermal layers so formed. However that may be, it seems clear that the size of the human ovum is due mainly to the rapid growth of this cavity, which, as future stages show, is the extra-embryonic portion of the body-cavity, the splitting or vacuolization of the
Fig. 38.  -  Diagrams to show the Probable Relationships of the Parts in the Embryos Represented in Figs. 29, C, and 37. Ac, Amniotic cavity; C, extra-embryonic body-cavity; Me, (in figure to the left) mesoderm, (in figure to the right) somatic mesoderm; Me, splanchnic mesoderm; D, digestive tract; En, endoderm; T, trophoblast. The broken line in the mesoderm of the figure to the left indicates the line along which the splitting of the mesoderm occurs.
mesoderm by which it is probably formed being the precocious appearance of the typical splitting of the mesoderm to form the embryonic body-cavity which, as will be seen in a subsequent chapter, takes place only at a later stage of development. From now on the trophoblast and the layer of mesoderm lining it may together be spoken of as the chorion, the mesoderm layer being termed the chorionic mesoderm.
A little older again than the Peters and Herzog ova are those described by Strahl and Beneke and by von Spee (Embryo v. H.), the chorionic cavity of the former two having an average diameter
of about 2.4 mm., while the corresponding size of the latter two was somewhat less than 4.0 mm. Notwithstanding the considerable increase in the size of these older ova, due to the continued increase in the size of the extra-embryonic ccelom, the embryos are but
Fig. 39.  -  The Embryo v. H. of von Spee. The Left Half of theT Chorion has
been Removed to show the Embryo. a, Amniotic cavity; b, belly-stalk; ch, chorion; d, yolk-sac; e, extra-embryonic ccelom; k y embryonic disk; 2, chorionic villus.  -  (von Spee.)
little advanced beyond the stage shown by the Peters embryo. The thickening of the chorionic mesoderm that encloses the amniotic cavity has increased in size and now forms a pedicle, known as the belly-stalk (Fig. 39, 6), at the extremity of which is the yolk-sac
Fig. 40.  -  Embryo from the Beneke Ovum, the Roof of the Amniotic Cavity
having been Removed. From a model, b, Belly-stalk; p.g., primitive groove; y, yolk-sac  -  (Strahl and Beneke.)
(d). Furthermore, the amniotic cavity (a) now lies somewhat excentrically in this pedicle, being near what may be termed its anterior surface, and the entire embryo projects like a papilla from the inner surface of the chorion into the extra-embryonic ccelom. Fig. 40 is
from a model of the Beneke embryo, detached from the chorion by cutting through the belly-stalk, and with the roof of the amniotic cavity removed. The dorsal surface of the embryo, thus exposed, is an oval disk, resting, as it were, on the yolk-sac, and quite smooth except for a slight longitudinal groove upon its posterior portion. This is the primitive groove and sections passing through it show the primitive streak, consisting of a sheet of mesoderm interposed between the ectoderm and endoderm, as in the Peters embryo, and but poorly defined from the other two layers. From its anterior edge a median process extends forward for a short distance and is the head process (see p. 56). In front and to the sides of this there is as yet no mesoderm intervening between the ectoderm and endoderm.
Fig. 41.  -  Embryo from the Frassi Ovum, the Roof of the Amniotic Cavity
having been removed. From a model, b, belly-stalk; p.g., primitive groove; mg, medullary groove; n, neuren
teric canal.  -  (Frassi.)
The embryonic disk of the Beneke embryo measured 0.75 mm. in length. That of an embryo described by Frassi (Fig. 41) was 1. 1 7 mm. in length, and in correspondence with its greater size, it presents some advances in structure that are of interest. As in the younger embryo one sees a distinct primitive groove on the posterior portion of the embryonic disk, but the groove terminates anteriorly at a distinct pore (w) , which perforates the disk and opens ventrally into the yolk-sac. This is the neurenteric canal (see p. 58) and in front of it a groove extends forward in the median line almost to the anterior edge of the embryonic disk and is evidently the first
indication of the medullary groove, whose walls are destined to give rise to the central nervous system. Sections passing through the region of the medullary groove show, lying beneath it, the head process (Fig. 42, hp), already fused with the endoderm (compare p. 57), and on each side of the process is a plate of mesoderm (gm), representing the gastral mesoderm of lower forms (see Figs. 28 and 34) , but not as yet showing any indications of splitting into the two layers that bound the embryonic ccelom (see p. 59).
Fig. 42.  -  Section through the Frassi Embryo just in Front of the Neuren
teric Canal. am, Amniotic cavity; gm, gastral mesoderm; hp, head process; mp, medullary plate; ys>
yolk-sac.  -  (Frassi.)
This is just beginning to appear in an embryo, also described by von Spee and known as embryo Gle. It measured 1.54 mm. in length and is closely similar, in general appearance, to an embryo described by Eternod and measuring 1.34 mm. in length (Fig. 43). It differs from the Frassi embryo most markedly in that the posterior portion of the embryonic disk, that is to say the primitive streak region, is bent ventrally so. as to lie almost at a right angle with the anterior portion. As a result the belly-stalk arises from the ventral surface of the embryo instead of from its posterior extremity, near which the opening of the neurenteric canal (Fig. 43, nc) is now situated, almost the whole length of the surface seen in dorsal view being occupied by the medullary groove (m), which, in the embryo Gle, is bounded laterally by distinct ridges, the medullary folds.
Fig. 43.  -  Embryo 1.34 mm. Long.
al Allantois; am, amnion; bs, belly-stalk; h, heart; m, medullary groove; tic neuren
tenc canal; pc, caudal protuberance; ps, primitive streak; ys, yolk-stalk. -  (Eternod.)
7 2
In the Kromer embryo Klb (Fig. 44), measuring i.8 mm. in length, a new feature has made its appearance. The medullary folds have become quite high, and lateral to them there is on each side a series of five or six oblong elevations, which represent what are termed mesodermic somites and are due to divisions of the underlying mesoderm.
Fig. 44.  -  Model of the Kromer Embryo Klb seen from the Dorsal Surface, the Roof of the Amniotic Cavity having been Removed.  -  (Keibel and Elze.)
Instead of proceeding with a description of the external form of still older embryos it will be convenient to consider the further development of certain structures whose appearance has already been noted, namely, the head process, the medullary folds and the mesodermic somites, and first of all • the medullary folds may be considered.
The Medullary Folds.  -  The two folds are continuous anteriorly, but behind they are at first separate, the anterior portion of the primitive streak lying between them. In forms, such as the Reptilia, which possess a distinct blastopore, this opening lies in the interval between the two, and consequently is in the floor of the medullary groove, and in the mammalia, even though no well-defined blastopore is formed, yet at the time of the formation of the medullary fold an opening breaks through at the anterior end of the primitive streak in the region of Hensen's node, and places the cavity lying below the endoderm in communication with the space bounded by the medullary folds. The canal so formed is termed the neurenteric
canal (Figs. 43 and 45, nc) and is so called because it unites what will later become the central canal of the nervous system with the intestine (enteron). The significance of this canal has already been discussed (p. 58) ; it is of very brief persistence, closing at an early stage of development so as to leave no trace of its existence.
Fig. 45.  -  Diagram of a Longitudinal Section through the Embryo Gle, Measuring 1.54 mm. in Length. al, Allantois; am, amnion; B, belly-stalk; ch, chorion; h, heart; nc, neurenteric canal; V, chorionic villi; Y, yolk-sac.  -  (vonSpee.)
As development proceeds the medullary folds increase in height and at the same time incline toward one another (Fig. 44), so that their edges finally come into contact and later fuse, the two ectodermal layers forming the one uniting with the corresponding layers of the other (Fig. 46). By this process the medullary groove becomes converted into a medullary canal which later becomes the
central canal of the spinal cord and the ventricles of the brain, the ectodermal walls of the canal thickening to give rise to the central nervous system. The closure of the groove does not, however, take place simultaneously along its entire length, but begins in what corresponds to the neck region of the adult and thence proceeds both
Fig. 46.  -  Diagrams showing the Manner of the Closure of the Medullary
anteriorly and posteriorly, the extension of the fusion taking place rather slowly, however, especially anteriorly, so that an anterior opening into the otherwise closed canal can be distinguished for a considerable period (Fig. 53).
The Noto chord.  -  While these changes have been taking place in the ectoderm of the median line of the embryonic disk, modifications of the subjacent endoderm have also occurred. This endoderm, it will be remembered, was formed by the head process of the primitive streak, and was a plate of cells continuous at the sides with the primary endoderm and extending forward as far as what will eventually be the anterior part of the pharynx. Along the line of its junction with the primary endoderm it gives rise to the plates of gastral mesoderm (Fig. 28), while the remainder of it produces an
important embryonic organ known as the notochord or chorda dorsalis and on this account is sometimes termed the chorda endoderm.
After the separation of the plates of gastral mesoderm the chorda endoderm, which is at first a flat band, becomes somewhat curved (Fig. 47, A), so that it is concave on its under surface, and, the curvature increasing, the edges of the plate come into contact and finally fuse together (Fig. 47, B), the edges of the primary endoderm at the same time uniting beneath the chordal tube so formed, so that this layer becomes a continuous sheet, as it was at its first appearance.
Fig. 47.  -  Transverse Sections through Mole Embryos, showing the Formation
of the Notochord. ec, Ectoderm; en, endoderm; m, mesoderm; nc. notochord.  -  (Heape.)
The lumen which is at first present in the chordal tube is soon obliterated by the enlargement of the cells which bound it, and these cells later undergo a peculiar transformation whereby the chordal tube is converted into a solid elastic rod surrounded by a cuticular sheath secreted by the cells. The notochord lies at first immediately beneath the median line of the medullary groove, between the ectoderm and the endoderm, and has on either side of it the mesodermal plates. It is a temporary structure of which only rudiments persist in the adult condition in man, but it is a structure characteristic of all vertebrate embryos and persists to a more or less perfect extent in many of the fishes, being indeed the only axial
skeleton possessed by Amphioxus. In the higher vertebrates it is almost completely replaced by the vertebral column, which develops around it in a manner to be described later.
The Mesodermic Somites.  -  Turning now to the middle germinal layer, it will be found that in it also important changes take place during the early stages of development. The probable mode of development of the extra-embryonic mesoderm and body-cavity has already been described (p. 67) and attention may now be directed toward what occurs in the embryonic mesoderm. In both the Peters embryo and the embryo v.H described by von Spee this portion of the mesoderm is represented by a plate of cells lying between the ectoderm and endoderm and becoming continuous at the edges of the embryonic area with both the layer which surrounds the yolk-sac and, through the mesoderm of the belly-stalk, with the chorionic mesoderm (Fig. 37). It seems probable, since there is in these embryos no indication as yet of the formation of the chorda endoderm, that this plate of mesoderm corresponds to the prostomial mesoderm of lower forms. In older embryos, such as the embryo Gle of Graf Spee and the younger embryo described by Eternod (Fig. 43), the mesoderm no longer forms a continuous sheet extending completely across the embryonic disk, but is divided into two lateral plates, in the interval between which the ectoderm of the floor of the medullary groove and the chorda endoderm are in close contact (Fig. 48). These lateral plates represent the gastral mesoderm, whose origin has already been described (p. 59), and which apparently supplants the original prostomial mesoderm, whose fate in the human embryo is at present unknown. The changes which now occur have not as yet been observed in the human embryo, though they probably resemble those described in other mammalian embryos, and the phenomena which occur in the sheep may serve to illustrate their probable nature.
It has been seen that in the stage represented by the Frassi embryo a plate of mesoderm has formed on either side of the chorda endoderm, and that in a later stage, represented by the Kromer embryo Klb, a differentiation occurs in these plates leading to the
formation of mesodermic somites. These make their appearance in what will later be the cervical region of the embryo and their formation proceeds backward as the body of the embryo increases in length. A longitudinal groove appears on the dorsal surface of each lateral plate of mesoderm, marking off the more median thicker portion from the lateral parts (Fig. 48), which from this stage onward may be termed the ventral mesoderm. The median or dorsal portions then become divided transversely into a number of more or less cubical masses which are termed the protoverlebrce or, better,
Fig. 48.  -  Transverse Section through the Second Mesodermic Somite of a Sheep Embryo 3 mm. Long. am, Amnion; en, endoderm; I, intermediate cell-mass; mg, medullary groove; ms, mesodermic somite; so, somatic and sp, splanchnic layers of the ventral mesoderm.  -  (Bonnet.)
mesodermic somites (Fig. 48, ms). The cells of the somites and of the ventral mesoderm, are at first stellate in form, but later become more spindle-shaped, and those near the center of each somite and those of the ventral mesoderm arrange themselves in regular layers so as to enclose cavities which appear in these regions (Fig. 48). Each original lateral plate of gastral mesoderm thus becomes divided longitudinally into three areas, a more median area composed of mesodermic somites, lateral to this a narrow area underlying the original longitudinal groove which separated the somite area from the ventral mesoderm and which from its position is termed the intermediate cell-mass (Fig. 48, 1) , and, finally, the ventral mesoderm. This last portion is now divided into two layers, the
dorsal of which is termed the somatic mesoderm, while the ventral one is known as the splanchnic mesoderm (Fig. 48, so and sp; and Fig. 49) , the cavity which separates these two layers being the embryonic body-cavity or pleuroperitoneal cavity (coslom) , which will eventually give rise to the pleural, pericardial and peritoneal cavities of the adult as well as the cavity of each tunica vaginalis testis.
Fig. 49.  -  Transverse Section of an Embryo of 2.5 mm. (See Fig. 53) showing on either side of the medullary canal a mesodermic somite, the interMEDIATE Cell-mass, and the Ventral Mesoderm.  -  (vonLenhossek.)
Beginning in the neck region, the formation of the mesodermic somites proceeds posteriorly until finally there are present in the human embryo thirty-eight pairs in the neck and trunk regions of the body, and, in addition, a certain number are developed in what is later the occipital region of the head. Exactly how many of these occipital somites are developed is not known, but in the cow four have been observed, and there are reasons for believing that the same number occurs in the human embryo.
In the lower vertebrates a number of cavities arranged in pairs occur in the more anterior portions of the head and have been homologized with mesodermic somities. Whether this homology be perfectly correct or not,
these head-cavities, as they are termed, indicate the existence of a division of the head mesoderm into somites, and although practically nothing is known as to their existence in the human embryo, yet, from the relations in which they stand to the cranial nerves and musculature in the lower forms, there is reason to suppose that they are not entirely unrepresented
\\'W^;  -  M
.*$'$te$&\& P
1 • ;
1 - -4 ;
Fig. 50.  -  Transverse Section of an Embryo of 4.25 mm. at the Level of the Arm
Rudiment. A, Axial mesoderm of arm; Am, amnion; il, inner lamella of myotome; M, myotome; me, splanchnic mesoderm; ol, outer lamella of myotome; Pn, place of origin of pronephros;^ sclerotome; S 1 , defect in wall of myotome due to separation of the sclerotome; st, stomach ; Vu, umbilical vein.  -  (Kollmann.)
The mesodermic somites in the earliest human embryos in which they have been observed contain a completely closed cavity, and this is true of the majority of the somites in such a form as the sheep. In the four first-formed somites in this species, however, the somite cavity is at first continuous with the pleuroperitoneal
cavity and only later becomes separated from it, and in lower vertebrates this continuity of the somite cavities with the general bodycavity is the rule. The somite cavities are consequently to be regarded as portions of the general pleuroperitoneal cavity which have secondarily been separated off. They are, however, of but short duration and early become filled up by spindle-shaped cells derived from the walls of the somites, which themselves undergo a differentiation into distinct portions. The cells of that portion of the wall of each somite which is opposite the notochord become spindleshaped and grow inward toward the median line to surround the notochord and central nervous system, and give rise eventually to the lateral half of the body of a vertebra and the corresponding portion of a vertebral arch. This portion of the somite is termed a sclerotome (Fig. 50, S), and the remainder forms a muscle plate or myotome (M) which is destined to give rise to a portion of the voluntary musculature of the body. The outer wall of the somite has been generally believed to take part in the formation of the cutis layer of the integument and hence has been termed the cutis plate or dermatome, but it seems probable that it becomes entirely transformed into muscular tissue.
The intermediate cell-mass in the human embryo, as in lower forms, partakes of the transverse divisions which separate the individual mesodermic somites. From one portion of the tissue in most of the somites (Fig. 50, Pri) the provisional kidneys or Wolffian bodies develop, this portion of each mass being termed a nephrotome, while the remaining portion gives rise to a mass of cells showing no tendency to arrange themselves in definite layers and constituting that form of mesoderm which has been termed mesenchyme (see p. 61). These mesenchymatous masses become converted into connective tissues and blood-vessels.
The ventral mesoderm in the neck and trunk regions never becomes divided transversely into segments corresponding to the mesodermic somites, differing in this respect from the other portions of the gastral mesoderm. In the head, however, that portion of the middle layer which corresponds to the ventral mesoderm of
the trunk does undergo a division into segments in connection with the development of the branchial arches and clefts (see p. 90). A consideration of these segments, which are known as the branchiomeres, may conveniently be postponed until the chapters dealing with the development of the cranial muscles and nerves, and in what follows here attention will be confined to what occurs in the ventral mesoderm of the neck and trunk.
Its splanchnic layer (Fig. 51, vm), applies itself closely to the endodermal digestive tract, which is constricted off from the dorsal portion of the yolk-sac, and becomes converted into mesenchyme out of which the muscular coats of the digestive tract develop. The cells which line the pleuroperitoneal cavity, however, retain their arrangement in a layer and form a part of the serous lining of the peritoneal and other serous cavities, the remainder of the lining being formed by the corresponding cells of the somatic layer; and in the abdominal region the superficial cells, situated near the line where the splanchnic layer passes into the somatic, and in close proximity to the nephrotome of the intermediate cell-mass, become columnar in shape and are converted into reproductive cells.
The somatic layer, if traced peripherally, becomes continuous at the sides with the layer of mesoderm which lines the outer surface of the amnion (Fig. 50) and posteriorly with the mesoderm of the belly-stalk. That portion of it which lies within the body of the embryo, in addition to giving rise to the serous lining of the parietal layer of the pleuroperitoneum, becomes converted into mesenchyme, which for a considerable length of time is clearly differentiated into two zones, a more compact dorsal one which may be termed the somatic layer proper, and a thinner, more ventral vascular zone which is termed the membrana reuniens (Fig. 51). In the earlier stages the somatic layer proper does not extend ventrally beyond the line which passes through the limb buds and it grows out into these buds to form an axial core for them, in which later the skeleton of the limb forms. The remainder of the mesoderm lining the sides and ventral portions of the body-wall is at first formed from the membrana reuniens, but as development proceeds the somatic 6
layer gradually extends more ventrally and displaces, or, more properly speaking, assimilates into itself, the membrana reuniens until finally the latter has completely disappeared.
It is to be noted that no part of the voluntary musculature of the lateral and ventral walls of the neck and trunk is derived from the somatic layer; it is formed entirely from the myotomes which gradually extend ventrally (Fig. 51) and finally come into contact with their fellows of the opposite side in the mid-ventral line.
Fig. 51.  -  Diagrams Illustrating the History of the Gastral Mesoderm.
dM, dorsal portion of myotome; gr, genital ridge; I, intestine; M, myotome, mr, membrana reuniens; N, nervous system; SC, sclerotome; Sm, somatic mesoderm; vm, splanchnic mesoderm; vM, ventral portion of myotome; Wd, Wolffian duct.
Whether the voluntary musculature of the limbs is also derived from the myotomes is at present doubtful. It has been very generally believed that the myotomes in their growth ventrally sent prolongations into the limb buds which invested the axial core of mesenchyme and eventually gave rise to the voluntary muscles. The actual existence of the prolongations of the myotomes and their conversion into the limb musculature has, however, not yet been observed and it is quite possible that the limb musculature may be derived from the axial core of somatic mesoderm from which the limb skeleton develops.
The appearance of the mesodermic somites is an important
phenomenon in the development of the embryo, since it influences fundamentally the future structure of the organism. If each pair of mesodermic somites be regarded as a structural unit and termed a metamere or segment, then it may be said that the body is composed of a series of metameres, each more or less closely resembling its fellows, and succeeding one another at regular intervals. Each somite differentiates, as has been stated, into a sclerotome and a myotome, and, accordingly, there will primarily be as many vertebra? and muscle segments as there are mesodermic somites, or, in other words, the axial skeleton and the voluntary muscles of the trunk are primarily metameric. Nor is this all. Since each metamere is a distinct unit, it must possess its own supply of nutrition, and hence the primary arrangement of the blood-vessels is also metameric, a branch passing off on either side from the main longitudinal arteries and veins to each metamere. And, further, each pair of muscle segments receives its own nerves, so that the arrangement of the nerves, again, is distinctly metameric.
It is to be noted that this metamerism is essentially resident in the dorsal mesoderm, the segmentation shown by structures derived from other embryonic tissues being secondary and associated with the relations of these structures to the mesodermic somites. The metamerism is most distinct in the neck and trunk regions, and at first only in the dorsal portions of these regions, the ventral portions showing metamerism only after the extension into them of the myotomes. But there is clear evidence that the arrangement extends also into the head, and that a portion of its mesoderm is to be regarded as composed of metameres. It has been seen that in the notochordal region of the head of lower vertebrates mesodermic somites are present, while anteriorly in the prechordal region there are headcavities which resemble closely the mesodermic somites, and are probably directly comparable to the somites of the trunk. There is reason, therefore, for believing that the fundamental arrangement of the dorsal mesoderm in all parts of the body is metameric, but though this arrangement is clearly defined in early embryos, it loses distinctness in later periods of development. But even in the
adult the original metamerism is clearly indicated in the arrangement of the nerves and of parts of the axial skeleton, and careful study frequently reveals indications of it in highly modified muscles and blood-vessels.
In the head the development of the branchial arches and clefts produces a series of parts presenting many of the peculiarities of metameres, and, indeed, it has been a very general custom to regard them as expressions of the general metamerism which prevails throughout the body. It is to be noted, however, that they are produced by the segmentation of the ventral mesoderm, a structure which in the neck and trunk regions does not share in the general metamerism, and, furthermore, recent observations on the cranial nerves seem to indicate that these branchiomeres cannot be regarded as portions of the head metameres or even as structures comparable to these. They represent, more probably, a second metamerism superposed upon the more general one, or, indeed, possibly more primitive than it, but whose relations can only be properly understood in connection with a study of the cranial nerves.
In addition to many of the papers cited in the list at the close of Chapter II, the following may be mentioned: C. R. Bardeen: " The Development of the Musculature of the Body Wall in the Pig,
etc.," Johns Hopkins Hosp. Rep., ix, 1900. T. H. Bryce and J. H. Teacher: " Contributions to the Study of the Early Development and Imbedding of the Human Ovum," Glasgow, 1908. A. C. F. Eternod: "Communication sur un ceuf humain avec embryon excessive
ment jeune," Arch. Ital. de Biologie, xxn, 1895. A. C. F. Eternod: "II y a un canal notochordal dans l'embryon humain," Anat.
Anzeiger, xvi, 1899. Fetzer: "Ueber ein durch Operation gewonnenes menschliches Ei das in seiner
Entwickelung etwa dem Peterssehen Ei entspricht," Verh. Anat. Gesellschaft,
xxiv, 1910. L. Frassi: "Weitere Ergebnisse des Studiums eines jungen menschlichen Eies in
situ," Arch.f. mikr. Anat., lxxi, 1908. W. Heape: "The Development of the Mole (Talpa Europaea)," Quarterly Journ.
Microsc. Science, xxvn, 1887. M. Herzog: "A Contribution to our Knowledge of the Earliest Known Stages of
Placentation and Embryonic Development in Man," Amer. Journ. Anat., ix, 1909.
F. Keibel: "Zur Entwickelungsgeschichte der Chorda bei Saugern (Meerschwein
chen und Kaninchen)," Archiv fur Anat. und Physiol., Anat. Abth., 1889. S. Kaestner: "Ueber die Bildung von animalen Muskelfasern aus dem Urwirbel,"
Arch, filr Anat. und Phys., Anat. Abth., Suppl., 1890. J. Kollmann: "Die Rumpfsegmente menschlicher Embryonen von 13 bis 35 Unvir
beln," Archiv filr Anat. und Physiol., Anat. Abth., 1891. H. Peters: "Ueber die Einbettung des menschlichen Eies und das friiheste bisher
bekannte menschliche Placentarstadium," Leipzig und Wien, 1899. F. Graf von Spee: " Beobachtungen an einer menschlichen Keimscheibe mit
offener Medullarrinne und Canalis neurentericus," Arch.f. Anat. u. Phys., Anat.
Abth., 1889. F. Graf von Spee: "Ueber friihe Entwicklungsstufen des menschlichen Eies,"
Arch.f. Anat. u. Phys., Anat. Abth., 1896. H. Strahl and R. Beneke: "Ein junger menschlicher Embryo," Wiesbaden, 1910. J. W. VAN Wijhe: "Ueber die Mesodermsegmente des Rumpfes und die Entwick
lung des Excretionsystems bei Selachiern," Archiv fur mikrosk. Anat., xxxin,
1889. K. W. Zimmermann: " Ueber Kopfhohlenrudimente beim Menschen," Archiv filr
mikrosk. Anat., liii, 1898.
In the preceding chapter descriptions have been given of human embryos representing the earlier known stages and the development of the general form of the human embryo has been traced up to the time when the mesodermic somites have made their appearance. It will now be convenient to continue the history of the general development up to the stage when the embryo becomes a fetus.
In the earlier stages, that is to say up to that represented by the Eternod embryo (Fig. 43), the embryonic disk may be described as floating upon the surface of the yolk-sac, and while this description still holds good for the Eternod embryo a distinct groove may be seen in that embryo between the peripheral portions of the embryonic disk and the upper part of the sac. This groove marks the beginning of the separation or constriction of the embryo from the yolk-sac, the result of which is the transformation of the discoidal embryonic portion of the embryonic disk into a cylindrical structure. Primarily this depends upon the deepening of the furrow which surrounds the embryonic area, the edges of this area being thus bent in on all sides toward the yolk-sac. This bending in proceeds most rapidly at the anterior end of the body, as shown in the diagrams (Fig. 52), and less rapidly at the posterior end where the bellystalk is situated, and produces a constriction of the yolk-sac, the portion of this structure nearest the embryonic disk becoming enclosed within the body of the embryo to form the digestive tract, while the remainder is converted into a pedicle-like portion, the yolk-stalk, ' at the extremity of which is the yolk-vesicle. The further continuance of the folding in of the edges of the embryonic area leads to an almost complete closing in of the embryonic ccelom
and reduces the opening through which the yolk-stalk and bellystalk communicate with the embryonic tissues to a small area known as the umbilicus.
In the Kromer embryo Klb (Fig. 44) this separation of the embryo proper from the yolk-sac has proceeded to such an extent that both extremities of the embryonic disk are free from the yolk-sac, and the anterior extremity is bent ventrally almost at a right angle to
Fig. 52.  -  Diagrams Illustrating the Constriction of the Embryo from the
Yolk-sac. A and C are longitudinal, and B and D transverse sections. B is drawn to a larger scale
than the other figures.
the rest of the disk, producing what is termed the vertex bend, a feature characteristic of all later embryos. The marked development in this embryo of the medullary folds and the occurrence of mesodermic somites have already been mentioned (p. 72).
Somewhat more advanced is the Bulle embryo described by Kollmann and shown from the side and dorsally in Fig. 53, the greater part of the yolk-sac having been removed as well as the most of the amnion. The embryo measured about 2.5 mm. in length and showed a considerable increase in the number of mesodermic somites, there being about fourteen of them on either side. Pos
teriorly the medullary groove has become converted into a medullary canal by the medullary folds meeting over it and fusing, but anteriorly it is still open. The vertex bend is well marked and
M^' L rX. j
Fig. 53.  -  Embryo 2.5 mm. Long.
om, Amnion; B, belly-stalk; h, heart; M, closed, and M', still open portions of the
medullary groove; Om, vitelline vein; OS, oral fossa; Y, yolk-sac.  -  (Kallmann.)
immediately behind the tip of the head, on the ventral surface of the body, there may be seen a well-marked depression, the oral fossa, between which and the anterior surface of the yolk-sac is a rounded
8 9
Fig. 54.  -  Embryo Lr, 4.2 mm. Long.
am, Amnion; au, auditory capsule; B, belly-stalk; h, heart; LI, lower, and Ul, upper
limb; Y, yolk-sac.  -  (His.)
elevation due to the formation of the heart. Attention may be called to the fact that the position of this organ is far forward of that which it will eventually occupy, so that it must undergo a marked retrogression during later development.
As an example of a later stage. of development the embryo Lr of His, measuring 4.2 mm. in length, may be taken (Fig. 54). In this the constriction of the yolk-sac has progressed so far that its proximal portion may now be spoken of as the yolk-stalk. The mesodermic somites have undergone a further increase and have almost reached their final number, the vertex bend has become still more pronounced and the medullary groove, throughout its entire length, has been converted into the medullary canal, which, anteriorly, shows distinct enlargements and constrictions which foreshadow various portions of the future brain. The auditory organ, which made its appearance in earlier stages, has now become quite distinct, and a lateral bulging of the most anterior portion of the head indicates the position of the future eye.
In addition certain other important features have now appeared. Thus, about opposite the head a second bend, the nape bend, is becoming visible on the dorsal surface of the body and toward the posterior end a distinct sacral bend is evident. Secondly, a little posterior to the level of the nape bend a slight elevation is to be seen on the side of the body; this is the limb bud for the upper limb and a corresponding, though smaller, elevation in the region of the sacral bend represents the lower limb.
Thirdly, three grooves having a dorso-ventral direction have appeared on the sides of what will be the future pharyngeal region. These are representatives of a series of branchial clefts, structures that are of great morphological importance in the further development inasmuch as they determine to a large extent the arrangement of various organs of the head region. They represent the clefts which exist in the walls of the pharynx in fishes, through which water, taken in at the mouth, passes to the exterior, bathing on its way the gill filaments attached to the bars or arches, as they are termed, which separate successive clefts. Hence the name "bran
9 1
Fig. 55.  -  Floor of the Pharynx of Embryo B, 7 mm. Long. Ep, Epiglottis; Sp, sinus prsecervicalis; t 1 , tuberculum impar; t 2 , posterior portions of the tongue; I, II, III, and IV, branchial arches.  - (His.)
chial" which is applied to them, though in the mammals they never have respiratory functions to perform, but, appearing, persist for a time and then either disappear or are applied to some entirely different purpose. Indeed, in man they are never really clefts but merely grooves, and corresponding to each groove in the ectoderm there is also one in the subjacent endoderm of what will eventually be the pharyngeal region of the digestive tract, so that in the region of each cleft the ectoderm and endoderm are in close relation, being separated only by a very thin layer of mesoderm. In the intervals between successive clefts a more considerable amount of mesoderm is present (Fig. 55).
In the human embryo four clefts and five branchial arches develop on each side of the body, the last arch lying posteriorly to the fourth cleft and not being very sharply denned along its posterior margin.
As just stated, the clefts are normally merely grooves, and in later development either disappear or are converted into special structures. Occasionally, however, a cleft may persist and the thin membrane which forms its floor may become perforated so that an opening from the exterior into the pharynx occurs at the side of the neck, forming what is termed a branchial fistula. Such an abnormality is most frequently developed from the lower (ventral) part of the first cleft; normally this disappears, the upper portion of the cleft persisting, however, to form the external auditory meatus and tympanic cavity.
A further stage in the differentiation of these clefts and arches is shown by the embryo represented in Fig. 56. The nape bend has now increased to such an extent that the whole anterior part of the body is bent at a right angle to the middle part and the entire embryo is coiled in a spiral manner. The limb buds are much more distinct than in the previous stage and four branchial arches are now present; the second and third have become more defined and
a strong process has developed from the dorsal part of the anterior border of the first one, which has thus become somewhat <3 -shaped. The anterior limb of each V is destined to give rise to the upper jaw, and hence is known as the maxillary process, while the posterior limb represents the future lower jaw and is termed the mandibular process.
M -  -  -  I - 
Fig. 56. -  Embryo Backer, 7.3 mm. in Length. X5.  -  (Keibefand Ehe.)
In the stage represented by this embryo the closing in of the embryonic ccelom has progressed to such a degree that only a small opening is left in the ventral body-wall of the embryo through which the yolk-stalk and its accompanying vessels and the belly-stalk pass. Indeed the margins of the umbilicus may have begun to be prolonged outward over these structures, enclosing them in a cylindrical investment, the first stage of what will later be the umbilical cord being thus established.
Leaving aside for the present all consideration of the further development of the limbs and branchial arches, the further evolution of the general form of the body may be rapidly sketched. In an embryo (Fig. 57) from Ruge's collection, described and figured by His and measuring 9.1 mm. in length,* the prolongation of the
Fig. 57.  -  Embryo 9.1 mm. Long. LI, Lower limb; U, umbilical cord; Ul, upper limb; Y, yolk-sac.  -  (His.)
margins of the umbilicus has increased until more than half the yolk-stalk has become enclosed within the umbilical cord. The nape and sacral bends are still very pronounced, although the embryo is beginning to straighten out and is not quite so much coiled as in the preceding stage. At the posterior end of the body there has
* This measurement is taken in a straight line from the most anterior portion of the nape bend to the middle point of the sacral bend and does not follow the curvature of the embryo. It may be spoken of as the nape-rump length and is convenient for use during the stages when the embryo is coiled upon itself.
developed a rather abruptly conical tail filament, in the place of the blunt and gradually tapering termination seen in earlier stages, and a well-marked rotundity of the abdomen, due to the rapidly increasing size of the liver, begins to become evident.
In later stages the enclosure of the yolk- and belly-stalks within the umbilical cord proceeds until finally the cord is complete through the entire interval between the embryo and the wall of the ovum. At the same time the straightening out of the embryo continues, as may be seen in Fig. 58 representing the embryo xlv (Br 2 ) of His, which shows also, both in front of and behind the neck bend, a
Fig. 58.'  -  Embryo B r 2 , 13.6 mm. Long.  -  (His.)
distinct depression, the more anterior being the occipital and the more posterior the nape depression; both these depressions are the indications of changes taking place in the central nervous system. The tail filament has become more marked, and in the head region a slight ridge surrounding the eyeball and marking out the conjunctival area has appeared; a depression anterior to the nasal fossae marks off the nose from the forehead; and the external ear, whose development will be considered later on, has become quite distinct. This embryo had a nape-rump length of 13.6 mm.
In the embryos xxxv (S 2 ) and xcix (L 3 ) (Fig. 59, A and B) of His' collection the straightening out of the nape bend is proceeding, and indeed is almost completed in embryo xcix, which begins to resemble closely the fully formed fetus. The tail filament, somewhat reduced in size, still persists and the rotundity of the abdomen continues to be well marked. The neck region is beginning to be distinguishable in embryo S 2 and in embryo L 3 the eyelids have appeared as slight folds surrounding the conjunctival area. The
Fig. 59.  -  A, Embryo S 2 , 15 mm. Long (showing Ectopia of the Heart); B, Embryo L 3 , 17.5 mm. Long.  -  (His.)
nose and forehead are clearly defined by the greater development of the nasal groove and the nose has also become raised above the general surface of the face, while the external ear has almost acquired its final fetal form. These embryos measure respectively about 15 and 17.5 mm. in length.*
Finally, an embryo  -  again one of those described by His,
* The embryo S 2 presents a slight abnormality [in the great projection of the heart, but otherwise it appears to be normal.
9 6
namely, his lxxvti (Wt), having a length of 23 mm.  -  may be figured (Fig. 60) as representing the practical acquisition of the fetal form. This embryo dates from about the end of the second month of pregnancy, and from this period onward it is proper to use the term fetus rather than that of embryo. The changes which
Fig. 60.  -  Embryo Wt, 23 mm. Long.  -  (His.)
have been described in preceding stages are now complete and it remains only to be mentioned that the caudal filament, which is still prominent, gradually disappears in later stages, becoming, as it were, submerged and concealed beneath adjacent parts by the development of the buttocks. The incompleteness of the development of these regions in embryo Wt is manifest, not only from the
projection of the tail filament, but also from the external genitalia being still largely visible in a side view of the embryo, a condition which will disappear in later stages.
The Later Development of the Branchial Arches, and the Development of the Face.  -  In the embryo shown in Fig. 56, the four branchial clefts and five arches which develop in the human embryo are visible in surface views, but in the Ruge embryo (Fig. 57) it will be noticed that only the first two arches, the first with a welldeveloped maxillary process, and the cleft separating them can be
Fig. 61.  -  Head of Embryo of 6.9 mm. na, Nasal pit; ps, precervical sinus. -  (His.)
distinguished. This is due to a sinking inward of the region occupied by the three posterior arches so that a triangular depression, the sinus pracervicalis, is formed on each side of what will later become the anterior part of the neck region. This is well shown in an embryo (Br 3 ) described by His which measured 6.9 mm. in length and of which the anterior portion is shown in Fig. 61. The anterior boundary of the sinus (ps) is formed by the posterior edge 7
of the second arch and its posterior boundary by the thoracic wall, and in later stages these two boundaries gradually approach one another so as first of all to diminish the opening into the sinus and later to completely obliterate it by fusing together, the sinus thus becoming converted into a completely closed cavity whose floor is formed by the ectoderm covering the three posterior arches and the clefts separating these. This cavity eventually undergoes degeneration, no traces of it occurring normally in the adult, although
Fig. 62.  -  Face of Embryo of 8 mm. mxp, Maxillary process; np, nasal pit; os, oral fossa; pg, processus globularis. -  (His.)
certain cysts occasionally observed in the sides of the neck may represent persisting portions of it.
A somewhat similar process results in the closure of the ventral portion of the first cleft,* a fold growing backward from the posterior edge of the first arch and fusing with the ventral part of the anterior border of the second arch. The upper part of the cleft persists, however, and, as already stated, forms the external auditory meatus, the pinna of the ear being developed from the adjacent parts of the first and second arches (Figs. 58 and 59).
* See page 91, small type.
The region immediately in front of the first arch is occupied by a rather deep depression, the oral fossa, whose early development has already been noticed. In an embryo measuring 8 mm. in length (Fig. 62) the fossa (os) has assumed a somewhat irregular quadrilateral form. Its posterior boundary is formed by the mandibular processes of the first arch, while laterally it is bounded by the maxillary processes (mxp) and anteriorly by the free edge of a median plate, termed the nasal process, which on either side of the
Fig. 63.  -  Face of Embryo after the Completion of the Upper Jaw.  -  (His.)
median line is elevated to form a marked protuberance, the processus globular is (pg). The ventral ends of the maxillary processes are widely separated, the nasal process and the processus globulares intervening between them, and they are also separated from the globular processes by a deep and rather wide groove which anteriorly opens into a circular depression, the nasal pit (np).
Later on the maxillary and globular processes unite, obliterating the groove and cutting off the nasal pits  -  which have by this time deepened to form the nasal fossae  -  from direct communication with the mouth, with which, however, they later make new communications behind the maxillary processes, an indication of the anterior and posterior nares being thus produced.
Occasionally the maxillary and globular processes fail to unite on one or both sides, producing a condition popularly known as "harelip."
At the time when this fusion occurs the nasal fossa? are widely separated by the broad nasal process (Fig. 63), but during later development this process narrows to form the nasal septum and is gradually elevated above the general surface of the face as shown in Figs. 58-60. By the narrowing of the nasal process the globular processes are brought nearer together and form the portions of the upper jaw immediately on each side of the median line, the rest of the jaw being formed by the maxillary processes. In the meantime a furrow has appeared upon the mandibular process, running parallel with its borders (Fig. 59); the portion of the process in front of this furrow gives rise to the lower lip and is known as the lip ridge, while the portion behind the furrow becomes the lower jaw proper and is termed the chin ridge.
The Development of the Limbs.  -  As has been already pointed out, the limbs make their appearance in an embryo measuring about 4 mm. in length (Fig. 54) and are at first bud-like in form. As they increase in length they at first have their long axes directed parallel to the longitudinal axis of the body and become somewhat flattened at their free ends, remaining cylindrical in their proximal portions. A furrow or constriction appears at the junction of the flattened and cylindrical portions (Fig. 57), and later a second constriction divides the cylindrical portion into a proximal and distal moiety, the three segments of each limb  -  the arm, forearm, and hand in the upper limb, and the thigh, leg, and foot in the lower  -  being thus marked out. The digits are first indicated by the development of four radiating shallow grooves upon the hand and foot regions (Fig. 58),
and a transverse furrow uniting the proximal ends of the digital furrows indicates the junction of the digital and palmar regions of the hand or of the toes and body of the foot. After this stage is reached the development of the upper limb proceeds more rapidly than that of the lower, although the processes are essentially the same in both limbs. The digits begin to project slightly, but are at first to a very considerable extent united together by a web, whose further growth, however, does not keep pace with that of the digits, these thus coming to project more and more in later stages. Even in comparatively early stages the thumb, and to a somewhat slighter extent the great toe, is widely separated from the second digit (Figs. 59 and 60).
While these changes have been taking place the entire limbs have altered their position with reference to the axis of the body, being in stages later than that shown in Fig. 57 directed ventrally so that their longitudinal axes are at right angles to that of the body. From the figures of later stages it may be seen that it is the thumb (radial) side of the arm and the great toe (tibial) side of the leg which are directed forward; the plantar and palmar surfaces of the feet and hands are turned toward the body and the elbow is directed outward and slightly backward, while the knee looks outward and slightly forward. It seems proper to conclude that the radial side of the arm is homologous with the tibial side of the leg, the palmar surface of the hand with the plantar surface of the foot, and the elbow with the knee.
The limbs are, however, still in the quadrupedal condition, and they must later undergo a second alteration in position so that their long axes again become parallel with that of the body. This is accomplished by a rotation of the limbs around axes passing through the shoulders and hip-joints, together with a rotation about their longitudinal axes through an angle of 90 degrees. This axial rotation of the upper limb is, however, in exactly the opposite direction to that of the lower limb of the corresponding side, so that the homologous surfaces of the two limbs have entirely different relations, the radial side of the arm, for instance, being the outer side while the tibial side
of the leg is the inner side, and whereas the palmar surface of the hand looks ventrally, the plantar surface of the foot looks dorsally. In making these statements no account is taken of the secondaryposition which the hand may assume as the result of its pronation; the positions given are those assumed by the limbs when both the bones of their middle segment are parallel to one another.
It may be pointed out that the prevalent use of the physiological terms flexor and extensor to describe the surfaces of the limbs has a tendency to obscure their true morphological relationships. Thus if, as is usual, the dorsal surface of the arm be termed its extensor surface, then the same term should be applied to the entire ventral surface of the leg, and all movements of the lower limb ventrally should be spoken of as movements of extension and any movement dorsally as movements of flexion. And yet a ventral movement of the thigh is generally spoken of as a flexion of the hip-joint, while a straightening out of the foot upon the leg  -  that is to say, a movement of it dorsally  -  is termed its extension.
The Age of the Embryo at Different Stages.  -  The age of an
embryo must be dated from the moment of fertilization and from what has been said in preceding pages (pp. 27, 34) it is evident that it must be difficult to determine the exact date of this event from that of the cessation of the menses, or even when the date of the coition that resulted in pregnancy is known. And, furthermore, not only is the actual date of the beginning of development uncertain, but in the majority of known early human embryos the time of the cessation of development is also more or less uncertain, since so many of these embryos are abortions and their expulsion need not necessarily have immediately succeeded their death.
These various sources of uncertainty are of especial importance in the cases of embryos in the early stages of development, when a day more or less means much, and it seems probable that many of the estimated ages given for young embryos, based on the date of the last menstruation, are too low. This certainly is the case with the ages assigned to such embryos by His, who estimated embryos of 2.2 to 3.0 mm. to be two to two and one-half weeks old, those of 5.0 to 6.0 mm. to be about three and one-half weeks and those of 10.0 to 11.0 mm. to be about four and one-half weeks.
There are on record, however, a few cases in which the date of the fruitful coition is definitely known, and from these, few though they be, somewhat more definite information may be obtained. Thus it is fairly certain that the Bryce-Teacher ovum, with an embryo measuring about 0.15 mm. in length, was the result of a coition which took place sixteen days before the ovum was aborted, and one cannot be far astray in assuming the embryo to be about two weeks old. Similarly, an embryo described by Eternod and measuring 1.3 mm. in length was the result of a single coition occurring twentyone days previously and its age may be set at approximately three weeks or better at eighteen or nineteen days. A later embryo in which the nape bend and the coiling of the body had appeared and which measured 8.8 mm. in vertex-breech length, resulted from a single coitus that took place thirty-eight days before the abortion, so that the embryo may be regarded as having been somewhat more than five weeks old. These and two other similar cases may be combined into a table thus:
Length of embryo
Days intervening
Probable age in
in mm.
between coition
and abortion
About 0.15
i3- J 4
V. B. 8.8
V. B. 14.0
V. B. 25.0
If, on the basis of these figures, one may venture to estimate the age of embryos of other lengths those of 2.0 to 3.0 mm. may be supposed to belong to the fourth week of development, those of 5.0 to 6.0 vertex-breech length to the latter part of the fifth week, those of 10.0 mm. to the end of the sixth week and those of 25.0 to 28.0 mm. which are just passing into the fetus stage, to the end of the eighth week. As regards the later periods of development, the
limits of error for any date become of less importance. Schroder gives the following measurements as the average:
3d lunar month 70-90 mm.
4th lunar month ' 100-170 mm.
5th lunar month 180-270 mm.
6th lunar month 280-340 mm.
7th lunar month 350-380 mm.
8th lunar month 425 mm.
9th lunar month 467 mm.
10th lunar month 490-500 mm.
The data concerning the weight of embryos of different ages are as yet very insufficient, and it is well known that the weights of newborn children may vary greatly, the authenticated extremes being, according to Vierordt, 717 grams and 6123 grams. It is probable that considerable variations in weight occur also during fetal life. So far as embryos of the first two months are concerned, the data are too imperfect for tabulation; for later periods Fehling gives the following as average weights:
3d month 20 grams.
4th month 120 grams.
5th month 285 grams.
6th month 635 grams.
7th month 1220 grams.
8th month 1700 grams.
9th month 2240 grams.
10th month 3 2 5° grams.
and the results obtained by Jackson are essentially similar.
In addition to the papers of Bryce and Teacher, Eternod, Fetzer, Frassi, Herzog, Peters, Von Spee and Strahl and Beneke cited in the preceding chapter, the following may be mentioned:
Bremer: "Description of a 4 mm. Human Embryo," Amer. Journ. Anal., v, 1906. J. Broman: "Beobachtung eines menschlichen Embryos von beinahe 3 mm. Lange
mit specieller Bemerkung uber die bei demselben befindlichen Hirnfalten,"
Morpholog. Arbeiten, v, 1895. A. J. P. van den Broek: "Zur Kasuistik junger menschlicher Embryonen," Anal,.
Hefte, xliv, 191 1.
J. M. Coste: " Histoire generale et particuliere du developpement des corps organises,"
Paris, 1847-1859. W. E. Dandy: "A Human Embryo with Seven Pairs of Somites, Measuring about
2 mm. in Length," Amer. Joiirn. Anal., x, 1910. A. Ecker: "Beitrage zur Kenntniss der ausserer Formen jiingster menschlichen
Embryonen," Archiv fur Anat. und Physiol., Anat. Abth., 18S0. C. Elze: " Beschreibung eines menschlichen Embryos von zirka 7 mm. grosster Lange,"
Anat. Hefte, xxxv, 1907. C. Giacomini: "Un ceuf humain de 11 jours," Archives Hal. de Biologie, xxix, 1898. V. Hensen: "Beitrag zur Morphologie der Korperform und des Gehirns des
menschlichen Embryos," Archiv fur Anat. und Physiol., Anat. Abth., 1877. W. His: "Anatomie menschlicher Embryonen," Leipzig, 1880. F. Hochstetter: "Bilder der ausseren Korperform einiger menschlicher Embryonen
aus den beiden Ersten Monaten der Entwicklung," Munich, 1907. N. W. Ingalls: "Beschreibung eines menschlichen Embryos von 4.9 mm.," Arch.
fiir mikr. Anat., lxx, 1907. C. M. Jackson: " On the Prenatal Growth of the Human Body and the Relative Growth
of the Various Organs and Parts," Amer. Journ. Anat., ix, 1909. J. Janosik: "Zwei junge menschliche Embryonen," Archiv fiir mikrosk. Anat., xxx,
1887. H. E Jordan: "Description of a 5 mm. Human Embryo," Anat. Record, ill, 1909. P. Jung: "Beitrage zur friihesten Ei-einbettung beim menschlichen Weibe," Berlin,
1908. F. Keibel: "Ein sehr junges menschliches Ei," Archiv fiir Anat. und Physiol., Anat.
Abth., 1890. F. Keibel: "Ueber einen menschlichen Embryo von 6.8 mm. grosster Lange,"
Verhandl. Anatom. Gesellsch., xiii, 1899. F. Keibel and C. Elze: " Normentafeln zur Entwicklungsgeschichte der Wirbeltiere,"
Heft viii, 1 90S. J. Kollmann: "Die Korperform menschlicher normaler und pathologischer Embryonen," Archiv fur Anat. und Physiol., Anat Abth., Supplement, 18S9. A. Low: "Description of a Human Embryo of 13-14 Mesodermic Somites," Journ.
Anat. and Phys., xlii, 1908. F. P. Mall: "A Human Embryo Twenty-six Days Old," Journ. of Morphology, V,
1891. F. P. Mall: "A Human Embryo of the Second Week," Anat. Anzeiger, viii, 1893. F. P. Mall: "Early Human Embryos and the Mode of their Preservation," Bulletin of
the Johns Hopkins Hospital, XV, 1S94. C. S. Minot: "Human Embryology," New York, 1892. J. Muller: " Zergliederungen menschlicher Embryonen aus friiherer Zeit," Archiv
fiir Anat. und Physiol., 1830. C. Phisalix: "Etude d'un Embryon humain de 11 millimeters," Archives de zoolog.
experimentale et generale, Ser. 2, vi, 1888. H. Piper: "Ein menschlicher Embryo von 6.8 mm. Nackenlinie," Archiv fiir Anat.
und Physiol., Anat. Abth,, 1898.
C. Rabl: "Die Entwicklung des Gesichtes, Heft i, Das Gesicht der Saugetiere,
Leipzig, 1902. G. Retzitts: "Zur Kenntniss der Entwicklung der Korperformen des Menschen
wahrend der fotalen Lebensstufen," Biolog. Untersuch., xi, 1904. J. Tandler: "Ueber einen menschlichen Embryo von 38 Tage," Anat. Anzeiger,
xxxi, 1907. Allen Thompson: "Contributions to the History of the Structure of the Human
Ovum and Embryo before the Third Week after Conception, with a Description
of Some Early Ova," Edinburgh Med. and Surg. Journal, in, 1839. (See also
Froriep's Neue Notizen, xiu, 1840.) P. Thompson: "Description of a human embryo of twenty-three paired somites,"
Journ. Anat. and Phys., xli, 1907.
The conditions to which the embryos and larvse of the majority of animals must adapt themselves are so different from those under which the adult organisms exist that in the early stages of development special organs are very frequently developed which are of use only during the embryonic or larval period and are discarded when more advanced stages of development have been reached. This remark applies with especial force to the human embryo which leads for a period of nine months what may be termed a parasitic existence, drawing its nutrition from and yielding up its waste products to the blood of the parent. In- order that this may be accomplished certain special organs are developed by the embryo, by means of which it forms an intimate connection with the walls of the uterus, which, on its part, becomes greatly modified, the combination of embryonic and maternal structures producing what are termed the deciduce, owing to their being discarded at birth when the parasitic mode of life is given up.
Furthermore, it has already been seen that many peculiar modifications of development in the human embryo result from the inheritance of structures from more or less remote ancestors, and among the embryonic adnexes are found structures which represent in a more or less modified condition organs of considerable functional importance in lower forms. Such structures are the yolk-stalk and vesicle, the amnion, and the allantois, and for their proper understanding it will be well to consider briefly their development in some lower form, such as the chick.
At the time when the embryo of the chick begins to be constricted off from the surface of the large yolk-mass, a fold, consisting
of ectoderm and somatic mesoderm, arises just outside the embryonic area, which it completely surrounds. As development proceeds the fold becomes higher and its edges gradually draw nearer together over the dorsal surface of the embryo (Fig. 64, A, Af), and finally meet and fuse (Fig. 64, B and C), so that the embryo becomes enclosed within a sac, which is termed the amnion and is formed by the fusion of the layers which constituted the inner wall of the fold. The layers of the outer wall of the fold after fusion form part of the
Fig. 64.  -  Diagrams Illustrating the Formation of the Amnion and Allantois
in the Chick. Af, Amnion folds; Al, allantois; Am, amniotic cavity; Ds, yolk-sac.  -  (Cegenbaur.)
general ectoderm and somatic mesoderm which make up the outer wall of the ovum and together are known as the serosa, corresponding to the chorion of the mammalian embryo. The space which occurs between the amnion and the serosa is a portion of the extraembryonic ccelom and is continuous with the embryonic pleuroperitoneal cavity.
In the ovum of the chick, as in that of the reptile, the protoplasmic material is limited to one pole and rests upon the large yolk
mass. As development proceeds the germ layers gradually extend around the yolk-mass and eventually completely enclose it, the yolkmass coming to lie within the endodermal layer, which, together with the splanchnic mesoderm which lines it, forms what is termed the yolk-sac. As the embryo separates from the yolk-mass the yolksac is constricted in its proximal portion and so differentiated into a yolk-stalk and a yolk-sac, the contents of the latter being gradually absorbed by the embryo during its growth, its walls and those of the stalk being converted into a portion of the embryonic digestive tract.
In the meantime, however, from the posterior portion of the digestive tract, behind the point of attachment of the yolk-sac, a diverticulum has begun to form (Fig. 64, A, Al). This increases in size, projecting into the extra-embryonic portion of the pleuroperitoneal cavity and pushing before it the splanchnic mesoderm which lines the endoderm (Fig. 64, B and C) . This is the allantois, which, reaching a very considerable size in the chick and applying itself closely to the inside of the serosa, serves as a respiratory and excretory organ for the embryo, for which purpose its walls are richly supplied with blood-vessels, the allantoic arteries and veins.
Toward the end of the incubation period both the amnion and allantois begin to undergo retrogressive changes, and just before the hatching of the young chick they become completely dried up and closely adherent to the egg-shell, at the same time separating from their point of attachment to the body of the young chick, so that when the chick leaves the egg-shell it bursts through the driedup membranes and leaves them behind as useless structures.
The Amnion.  -  Turning now to the human embryo, it will be found that the same organs are present, though somewhat modified either in the mode or the extent of their development. A welldeveloped amnion occurs, arising, however, in a very different manner from what it does in the chick; a large yolk-sac occurs even though it contains no yolk; and an allantois which has no respiratory or excretory functions is present, though in a somewhat degenerated condition. It has been seen from the description of the earliest stages of development that the processes which occur in the lowe
forms are greatly abbreviated in the human embryo. The enveloping layer, instead of gradually extending from one pole to enclose the entire ovum, develops in situ during the stages immediately succeeding segmentation, and the extra-embryonic mesoderm, instead of growing out from the embryo to enclose the yolk-sac, splits off directly from the enveloping layer. The earliest stages in the development of the amnion are not yet known for the human embryo, but from the condition in which it is found in the Peters embryo (Fig. 37) and in the embryo v.H. of von Spee (Fig. 39) it is probable that it arises, not by the fusion of the edges of a fold, as in the chick, but by a vacuolization of a portion of the inner cellmass, as has been described as occurring in the bat (p. 54). It is, then, a closed cavity from the very beginning, the floor of the cavity being formed by the embryonic disk, its posterior wall by the anterior surface of the belly-stalk, while its roof and sides are thin and composed of a single layer of flattened ectodermal cells lined on the outside by a layer of mesoderm continuous with the somatic mesoderm of the embryo and the mesoderm of the belly-stalk (Fig. 65, A).
When the bending downward of the peripheral portions of the embryonic disk to close in the ventral surface of the embryo occurs, the line of attachment of the amnion to the disk is also carried ventrally (Fig. 65, B), so that when the constriction off of the embryo is practically completed, the amnion is attached anteriorly to the margin of the umbilicus and posteriorly to the extremity of the band of ectoderm lining what may now be considered the posterior surface of the belly-stalk, while at the sides it is attached along an oblique line joining these two points (Fig. 65, B and C, in which the attachment of the amnion is indicated by the broken line).
Leaving aside for the present the changes which occur in the attachment of the amnion to the embryo (see p. 116), it may be said that during the later growth of the embryo the amniotic cavity increases in size until finally its wall comes into contact with the chorion, the extra-embryonic body-cavity being thus practically obliterated (Fig. 65, D), though no actual fusion of amnion and
chorion occurs. Suspended by the umbilical cord, which has by this time developed, the embryo floats freely in the amniotic cavity, which is filled by a fluid, the liquor amnii, whose origin is involved in doubt, some authors maintaining that it infiltrates into the cavity from the maternal tissues, while others hold that a certain amount
Fig. 65.  -  Diagrams Illustrating the Formation of the Umbilical Cord.
The heavy black line represents the embryonic ectoderm; the dotted line represents the line of reflexion of the body ectoderm into that of the amnion. Ac, Amniotic cavity ; Al, allantois; Be, extra-embryonic ccelom; Bs, belly-stalk; Ch, chorion; P, placenta; Uc, umbilical cord; V, chorionic villi; Ys, yolk-sac.
of it at least is derived from the embryo. It is a fluid with a specific gravity of about 1.003 an( ^ contains about 1 per cent, of solids, principally albumin, grape-sugar, and urea, the last constituent probably coming from the embryo. When present in greatest quantity  -  that is to say, at about the beginning of the last month
of pregnancy  -  it varies in amount between one-half and threefourths of a liter, but during the last month it diminishes to about half that quantity. To protect the epidermis of the fetus from maceration during its prolonged immersion in the liquor amnii, the sebaceous glands of the skin at about the sixth month of development pour out upon the surface of the body a white fatty secretion known as the vernix caseosa.
During parturition the amnion, as a rule, ruptures as the result of the contraction of the uterine walls and the liquor amnii escapes as the "waters," a phenomenon which normally precedes the delivery of the child. As a rule, the rupture is sufficiently extensive to allow the passage of the child, the amnion remaining behind in the uterus, to be subsequently expelled along with the deciduae.
Occasionally it happens, however, that the amnion is sufficiently strong to withstand the pressure exerted upon it by the uterine contractions and the child is born still enveloped in the amnion, which, in such cases, is popularly known as the "caul," the possession of which, according to an old superstition, marks the child as a favorite of fortune.
As stated above, the liquor amnii varies considerably in amount in different cases, and occasionally it may be present in excessive quantities, producing a condition known as hydramnios. On the other hand, the amount may fall considerably below the normal, in which case the amnion may form abnormal unions with the embryo, sometimes producing malformations. Occasionally also bands of a fibrous character traverse the amniotic cavity and, tightening upon the embryo during its growth, may produce various malformations, such as scars, splitting of the eyelids or lips, or even amputation of a limb.
The Yolk-sac.  -  The probable mode of development of the yolk-sac in the human embryo, and its differentiation into yolk-stalk and yolk- vesicle have already been described (p. 86). When these changes have been completed, the vesicle is a small pyriform structure lying between the amnion and the chorionic mesoderm, some distance away from the extremity of the umbilical cord (Fig. 65, D), and the stalk is a long slender column of cells extending from the vesicle through the umbilical cord to unite with the intestinal tract of the embryo. The vesicle persists until birth and may be found among the decidual tissues as a small sac measuring from 3 to
10 mm. in its longest diameter. The stalk, however, early undergoes degeneration, the lumen which it at first contains becoming obliterated and its endoderm also disappearing as early as the end of the second month of development. The portion of the stalk which extends from the umbilicus to the intestine usually shares in the degeneration and disappears, but in about 3 per cent, of cases it persists, forming a more or less extensive diverticulum of the lower part of the small intestine, sometimes only half an inch or so in length and sometimes much larger. It may or may not retain connection with the abdominal wall at the umbilicus, and is known as Meckel's diverticulum.
This embryonic rudiment is of no little importance, since, when present, it is apt to undergo invagination into the lumen of the small intestine and so occlude it. How frequently this happens relatively to the occurrence of the diverticulum may be judged from the fact that out of one hundred cases of occlusion of the small intestine six were due to an invagination of the diverticulum.
In the reptiles and birds the yolk-sac is abundantly supplied with blood-vessels by means of which the absorption of the yolk is carried on, and even although the functional importance of the yolk-sac as an organ of nutrition is almost nil in the human embryo, yet it still retains a well-developed blood-supply, the walls of the vesicle, especially possessing a rich network of vessels. The future history of these vessels, which are known as the vitelline vessels, will be described later on.
The Allantois and Belly-stalk.  -  It has been seen that in reptilian and avian embryos the allantois reaches a high degree of development and functions as a respiratory and excretory organ by coming into contact with what is comparable to the chorion of the mammalian embryo. In man it is very much modified both in its mode of development and in its relations to other parts, so that its resemblance to the avian organ is somewhat obscured. The differences depend partly upon the remarkable abbreviation manifested in the early development of the human embryo and partly upon the fact that the allantois serves to place the embryo in relation with the 8
maternal blood, instead of with the external atmosphere, as is the case in the egg-laying forms. Thus, the endodermal portion of the allantois, instead of arising from the intestine and pushing before it a layer of splanchnic mesoderm to form a large sac lying freely in the extra-embryonic portion of the body-cavity, appears in the human embryo before the intestine has differentiated from the yolk-sac and pushes its way into the solid mass of mesoderm which forms the belly-stalk (Fig. 65, A). To understand the significance of this process it is necessary to recall the abbreviation in the human embryo of the development of the extra-embryonic mesoderm and body-cavity. Instead of growing out from the embryonic area, as it does in the lower forms, this mesoderm develops in situ by splitting off from the layer of enveloping cells and, furthermore, the extra-embryonic
body-cavity arises by a splitting of the mesoderm so formed before there is any trace of a splitting of the embryonic mesoderm (Fig. 38). The belly-stalk, whose development from a portion of the inner cell-mass has already been traced (p. 68), is to be regarded as a portion of the body of the embryo, since the ectoderm which covers one surface of it resembles exactly that of the embryonic disk and shows an extension backward of the medullary groove upon its surface (Fig. 66). The mesoderm, therefore, of the belly-stalk is to be regarded as a portion of the embryonic mesoderm which has not yet undergone a splitting into somatic and splanchnic layers, and, indeed, it never does undergo such a splitting, so that there is no body-cavity into which the endodermal allantoic diverticulum can grow.
But this does not account for all the peculiarities of the human allantois. In the birds, and indeed in the lower oviparous mammals, the endodermal portion of the allantois is equally developed with
Fig. 66.  -  Transverse Section THROUGH THE BELLY-STALK
of an Embryo of 2.15 mm.
Aa, Umbilical (allantoic) artery; All, allantois; am, amnion; Va, umbilical (allantoic) vein.  -  (His.)
the mesodermal portion, the allantois being an extensive sac whose cavity is rilled with fluid, and this is also true of such mammals as the marsupials, the rabbit, and the ruminants. In man, however, the endodermal diverticulum never becomes a sac-like structure, but is a slender tube extending from the intestine to the chorion and lying in the substance of the mesoderm of the belly-stalk (Fig. 65, D), the greater portion of which is to be regarded as homologous with the relatively thin layer of splanchnic mesoderm covering the endodermal diverticulum of the chick. An explanation of this disparity in the development of the mesodermal and endodermal portions of the human allantois is perhaps to be found in the altered conditions under which the respiration and secretion take place. In all forms, the lower as well as the higher, it is the mesoderm which is the more important constituent of the allantois, since in it the blood-vessels, upon whose presence the physiological functions depend, arise and are embedded. In the birds and oviparous mammals there are no means by which excreted material can be passed to the exterior of the ovum, and it is, therefore, stored up within the cavity of the allantois, the allantoic fluid containing considerable quantities of nitrogen, indicating the presence of urea. In the higher mammals the intimate relations which develop between the chorion and the uterine walls allow of the passage of excreted fluids into the maternal blood; and the more intimate these relations, the less necessity there is for an allantoic cavity in which excreted fluid may be stored up. The difference in the development of the cavity in the ruminants, for example, and man depends probably upon the greater intimacy of the union between ovum and uterus in the latter, the arrangement for the passage of the excreted material into the maternal blood being so perfect that there is practically no need for the development of an allantoic cavity.
The portion of the endodermal diverticulum which is enclosed within the umbilical cord persists until birth in a more or less rudimentary condition, but the intra-embryonic portion extending from the apex of the bladder to the umbilicus becomes converted into a solid cord of fibrous tissue termed the urachus.
Occasionally a lumen persists in the urachal portion of the allantois and may open to the exterior at the umbilicus, in which case urine from the bladder may escape at the umbilicus.
Since the allantois in the human embryo, as well as in the lower forms, is responsible for respiration and excretion, its blood-vessels are well developed. They are represented in the belly-stalk by two veins and two arteries (Fig. 66), known in human embryology as the umbilical veins and arteries. These extend from the body of the embryo out to the chorion, there branching repeatedly to enter the numerous chorionic villi by which the embryonic tissues are placed in relation with the maternal.
The Umbilical Cord.  -  During the process of closing in of the ventral surface of the embryo a stage is reached in which the embryonic and extra-embryonic portions of the body-cavity are completely separated except for a small area, the umbilicus, through which the yolk-stalk passes out (Fig. 65, B). At the edges of this area in front and at the sides the embryonic ectoderm and somatic mesoderm become continuous with the corresponding layers of the amnion, but posteriorly the line of attachment of the amnion passes up upon the sides of the belly-stalk (Fig. 65, B), so that the whole of the ventral surface of the stalk is entirely uncovered by ectoderm, this layer being limited to its dorsal surface (Fig. 66). In subsequent stages the embryonic ectoderm and somatic mesoderm at the edges of the umbilicus grow out ventrally, carrying with them the line of attachment of the amnion and forming a tube which encloses the proximal part of the yolk-stalk. The ectoderm of the belly-stalk at the same time extending more laterally, the condition represented in Fig. 65, C, is produced, and, these processes continuing, the entire belly-stalk, together with the yolk-stalk, becomes enclosed within a cylindrical cord extending from the ventral surface of the body to the chorion and forming the umbilical cord (Fig. 65, D).
From this mode of development it is evident that the cord is, strictly speaking, a portion of the embryo, its surfaces being completely covered by embryonic ectoderm, the amnion being carried
Fig. 67.  -  -Transverse Sections of the Umbilical Cord of Embryos of (A) 1.8 cm.
and (B) 25 cm. al, Allantois; c, coelom; ua, umbilical artery; uv, umbilical vein; ys, yolk-stalk.
during its formation further and further from the umbilicus until finally it is attached around the distal extremity of the cord.
In enclosing the yolk-stalk the umbilical cord encloses also a small portion of what was originally the extra-embryonic bodycavity surrounding the yolk-stalk. A section of the cord in an early stage of its development (Fig. 67, A) will show a thick mass of mesoderm occupying its dorsal region; this represents the mesoderm of the belly-stalk and contains the allantois and the umbilical arteries and vein (the two veins originally present in the belly-stalk having fused), while toward the ventral surface there will be seen a distinct cavity in which lies the yolk-stalk with its accompanying blood-vessels. The portion of this ccelom nearest the body of the embryo becomes much enlarged, and during the second month of development contains some coils of the small intestine, but later the entire cavity becomes more and more encroached upon by the growth of the mesoderm, and at about the fourth month is entirely obliterated. A section of the cord subsequent to that period of development will show a solid mass of mesoderm in which are embedded the umbilical arteries and vein, the allantois, and the rudiments of the yolk-stalk (Fig. 67, B).
When fully formed, the umbilical cord measures on the average 55 cm. in length, though it varies considerably in different cases, and has a diameter of about 1.5 cm. It presents the appearance of being spirally twisted, an appearance largely due, however, to the spiral course pursued by the umbilical arteries, though the entire cord may undergo a certain amount of torsion from the movements of the embryo in the later stages of development and may even be knotted. The greater part of its substance is formed by the mesoderm, the cells of which become stellate and form a recticulum, the meshes of which are occupied by connective-tissue fibrils and a mucous fluid which gives to the tissue a jelly-like consistence, whence it has received the name of Wharton's jelly.
The Chorion.  -  To understand the developmental changes which the chorion undergoes it will be of advantage to obtain some insight into the manner in which the ovum becomes implanted in
II 9
the wall of the uterus. Nothing is known as to how this implantation is effected in the case of the human ovum; it has already been accomplished in the youngest ovum at present known. But the process has been observed in other mammals, and what takes place in Spermophilus, for example, may be supposed to give a clue to what occurs in the human ovum. In the spermophile the ovum lies free in the uterine cavity up to a stage at which the vacuolization
* I
Fig. 68.  -  Successive Stages in the Implantation of the Ovum of the Spermophile . a, syncytial knob; k, inner cell-mass.  -  (Rejsek.)
of the central cells is almost completed (Fig. 68, A). At one region of the covering layer the cells become thicker and later form a syncytial projection or knob which comes into contact with the uterine mucosa (Fig. 68, B), and at the point of contact the mucosa cells undergo degeneration, allowing the knob to come into relation with the deeper tissues of the uterus (Fig. 68, C), the process apparently being one in which the mucosa cells are eroded by the syncytial knob. It seems probable that in the human ovum the process is at first of a similar nature and that as the covering layer cells come into
Fig. 69.  -  Diagrams Illustrating the Implantation of the Ovum. ac, amniotic cavity; bs, belly-stalk; cf, chorion frondosum; cl, chorion laeve;Jc, decidua capsularis; ic, inner cell-mass; s, space surrounding ovum which becomes the intervillous space; um, uterine mucosa; v, chorionic villus; ys, yolk-sac.
contact with the deeper layers of the uterus, these too are eroded, and, the uterine blood-vessels being included in the erosion process, an extravasation of blood plasma and corpuscles occurs in the vicinity of the burrowing ovum. In the meantime the ovum has increased considerably in size, its growth in these early stages being especially rapid, and the area of contact consequently increases in size, entailing continued erosion of the uterine mucosa. At the same time, too, the uterine tissues surrounding the ovum grow up around it, forming at first as it were a circular wall (Fig. 69, A), and eventually com
â– -K
^,^^f^>r%^^ c y
Fig. 70.  -  Section of an Ovum of i mm. A Section of the Embryo Lies in the
Lower Part of the Cavity of the Ovum.
D, Decidua; E.U., uterine epithelium; Sch, blood-clot closing the aperture left by
the sinking of the ovum into the uterine mucosa.  -  (From Strahl, after Peters.)
pletely enclose it, forming an envelope known as the decidua capsularis or rejiexa. The blood extravasation is now contained within a closed space bounded on the one hand by the uterine tissues and on the other by the wall of the ovum (Fig. 69, B).
The youngest known human ova have already reached approxi
mately this stage. Thus, the Peters ovum (Fig. 70) had already sunk deeply into the uterine mucosa, the point of entrance being indicated by a gap in the decidua capsularis, closed in this case by a patch of coagulated blood (Sch). The uterine tissues in the immediate vicinity of the ovum were much swollen and apparently somewhat necrotic and their blood-vessels could be seen to communicate with the space between the wall of the ovum and the maternal tissues. This space, however, was converted into an irregular network of blood lacunae by anastomosing cords of cells, which arose from the wall of the ovum and extended through the space to the maternal tissues ; these cords of cells are represented in Fig. 70 by the darker masses projecting from the wall of the ovum and scattered among the paler blood lacunae. This stage of implantation of the ovum is shown diagrammatically in Fig. 69, B, where, for simplicity's sake, the cell cords are represented merely as processes radiating from the ovum without reaching the maternal tissues.
The cell cords are derivatives of the trophoblast and are, therefore, of embryonic origin. If examined under a higher magnification than that shown in Fig. 70 they will be seen to be composed of an axial core of cells with distinct outlines, enclosed within a layer of protoplasm which lacks all traces of cell boundaries, although it contains numerous nuclei, being what is termed a syncytium or Plasmodium. The original trophoblast has thus become differentiated into two distinct tissues, a cellular one, which has been termed the cyto-trophoblast, and a plasmodial one, which, similarly, is known as the plasmodi-trophoblast and is the tissue that comes into contact with the maternal blood contained in the lacunar spaces and with the maternal tissues, in connection with these latter sometimes developing into masses of considerable extent. To this plasmoditrophoblast may be ascribed the active part in the destruction of the maternal tissues and probably also the absorption of the products of the destruction for the nutrition of the growing ovum. For up to this stage the ovum has been playing the role of a parasite thriving upon the tissues of^ its host.
The food material that the ovum thus obtains may conveniently
be termed the embryotroph and the type of placentation which obtains up to this stage and for some time longer may be termed the embryotrophic type. But even in the Peters ovum the preparation for another type has begun. In earlier stages the cell cords were entirely trophoblastic, but in this ovum (Fig. 70) processes from the chorionic mesoderm may be seen projecting into the bases of the cell cords, and in later stages these processes extend farther and farther into the axis of each cord, the anastomoses of the cords disappear and the cords themselves become converted into branching processes, the
Fig. 71.  -  Entire Ovum Aborted at about the Beginning of the Second Month. Xi 1/2.  -  (Grosser.)
chorionic villi, which project from the entire surface of the ovum (Fig. 71) into the surrounding space, which may now be termed the intervillous space, and are bathed by the maternal blood which it contains. Toward the maternal surface of the space some masses of the trophoblast still persist, uniting the extremities of certain of the villi to the enclosing uterine wall, such villi being termed fixation villi to distinguish them from the majority, which project freely into the intervillous space. Later, when the embryonic blood-vessels
develop, those associated with the allantois extend outward into the chorionic mesoderm and thence send branches into each villus. The second type of placentation, the hcemotrophic type, is thus established, the fetal blood contained in the vessels of the villi receiving nutrition through the walls of the villi from the maternal blood contained in the intervillous space, and, similarly, transferring waste products to it.
At first, as stated above, the villi usually cover the entire surface of the ovum, but later, as the ovum increases in size, those villi which are remote from the attachment of the belly-stalk to the chorion are placed at a disadvantage so far as their blood supply is concerned
Fig. 72.  -  Two Villi prom the Chorion of an Embryo of 7 mm.
and gradually disappear, and this process continues until, finally, only those villi are retained which are in the immediate region of the belly-stalk (Fig. 69, C), these persisting to form the fetal portion of the placenta. By these changes the chorion becomes differentiated into two regions (Fig. 69, C), one of which is destitute of villi and is termed the chorion lave, while the other provided with them, is known as the chorion frondosum.
Fig. 73.  -  Transverse Sections through Chorionic Villi in (4) the Fifth and (B) the Seventh Month of Development.
cf, Canalized fibrin; Ic, Langhans cells; s, syncytium.  -  (A which is more highly magnified than B, from Szymonowicz; B from Minot.)
Occasionally one or more patches of villi may persist in the area that normally becomes the chorion lseve and thus accessory placenta (-placenta succenturiatce) , varying in number and size, may be formed.
The villi when fully formed are processes of the chorion, branching profusely and irregularly (Fig. 72), and each consists of a core of mesoderm, containing blood-vessels, enclosed within a double layer of trophoblastic tissue (Fig. 73, A). The inner layer consists of a sheet of well defined cells arranged in a single series; it is derived from the cyto-trophoblast and forms what is known as the layer of Langhans cells. The outer layer is syncytial in structure and is formed from the plasmodi-trophoblast.
Fig. 74.  -  Mature Placenta after Separation from the Uterus. c, Cotyledons; eh, chorion, amnion, and decidua vera; urn, umbilical cord.  -  (Kollmann.)
As development proceeds the villi, which are at first distributed evenly over the chorion frondosum, become separated into groups termed cotyledons (Fig. 74) by the growth into the intervillous space of trabecular from the walls of the uterus, the fixation villi becoming connected with these septa as well as with the general uterine wall. The ectoderm of the villi also undergoes certain changes with advancing growth, the layer of Langhans cells disappearing except in small areas scattered irregularly in the villi, and the syncytium,
though persisting, undergoes local thickenings which become replaced, more or less extensively, by depositions of fibrin (Fig. 73, B, cf).
The changes which occur during the later stages of development in the chorion are very similar to those described for the villi.
Fig. 75.  -  Section through the Placental Chorion of an Embryo of Seven
Months. c, Cell layer; ep, remnants of epithelium; fb, fibrin layer; mes, mesoderm.  -  (Minot.)
Thus, the mesoderm thickens, its outermost layers becoming exceedingly fibrillar in structure, while the ectoderm differentiates into two layers, the outer of which is syncytial while the inner is cellular, and later still, as in the villi, the syncytial layer is replaced
in irregular patches by a peculiar form of fibrin which is traversed by flattened anastomosing spaces and to which the name canalized fibrin or fibrinoid has been applied (Fig. 75).
The Deciduae.  -  It has been pointed out (p. 26) that in connection with the phenomenon of menstruation periodic alterations occur in the mucous membrane of the uterus. If during one of these periods a fertilized ovum reaches the uterus, the desquamation
Fig. 76.  -  Diagram showing the Relations of the Fetal Membranes.
Am, Amnion; Ch, chorion; M, muscular wall of uterus; C, decidua capsularis; B,
decidua basalis; V, decidua vera; F, yolk-stalk.
of portions of the epithelium does not occur nor is there any appreciable hemorrhage into the cavity of the uterus; the uterine mucosa remains in what is practically the ante-menstrual condition until the conclusion of pregnancy, when, after the birth of the fetus, a considerable portion of its thickness is expelled from the uterus, forming what is termed the decidua. In other words, the sloughing of the
uterine tissue which concludes the process of menstruation is postponed until the close of pregnancy, and then takes place simultaneously over the whole extent of the uterus. Of course, the changes in the uterine tissues are somewhat more extensive during pregnancy than during menstruation, but there is an undoubted fundamental similarity in the changes during the two processes.
Fig. 77.  -  Surface View op Half of the Decldua Vera at the End of the Third
Week of Gestation.
d, Mucous membrane of the Fallopian tubes; ds, prolongation of the vera toward the
cervix uteri; pp., papillae; rf, marginal furrow. (Kollmann.)
The human ovum comes into direct apposition with only a small portion of the uterine wall, and the changes which this portion of the wall undergoes differ somewhat from those occurring elsewhere. Consequently it becomes possible to divide the deciduae into (1) a portion which is not in direct contact with the ovum, the decidua vera (Fig. 76, V) and (2) a portion which is. The latter portion is again 9
capable of division. The ovum becomes completely embedded in the mucosa, but, as has been pointed out, the chorionic villi reach their full development only over that portion of the chorion to which the belly-stalk is attached. The decidua which is in relation to this chorion frondosum undergoes much more extensive modifications than that in relation to the chorion laeve, and to it the name of decidua basalts (decidua serotina) (Fig. 76, B) is applied, while the rest of the decidua which encloses the ovum is termed the decidua capsularis (decidua rejlexa) (C).
The changes which give rise to the decidua vera may first be described and those occurring in the others considered in succession.
(a) Decidua vera.  -  On opening a uterus during the fourth or fifth month of pregnancy, when the decidua vera is at the height of its development, the surface of the mucosa presents a corrugated appearance and is traversed
Fig. 78.  -  Diagrammatic Sections of the Uterine Mucosa, A, in the Nonpregnant Uterus, and B, at the Beginning of Pregnancy. c, Stratum compactum; gl, the deepest portions of the glands; m, muscular layer; sp, stratum spongiosum.  -  (Kundrat and Engelmann.)
by irregular and rather deep grooves (Fig. 77). This appearance ceases at the internal orifice, the mucous membrane of the cervix uteri not forming a decidua, and the deciduae of the two surfaces of the uterus are separated by a distinct furrow known as the marginal groove.
In sections the mucosa is found to have become greatly thickened, frequently measuring i cm. in thickness, and its glands have undergone very considerable modification. Normally almost straight (Fig. 78, A), they increase in length, not only keeping pace with the thickening of the mucosa, but surpassing its growth, so that they become very much contorted and are, in addition, considerably dilated (Fig. 78, B). Near their mouths they are dilated, but not very much contorted, while lower down the reverse is the case, and it is possible to recognize three layers in the decidua, (1) a stratum compactum nearest the lumen of the uterus, containing the straight but dilated portions of the glands; (2) a stratum spongiosum, so called from the appearance which it presents in sections owing to the dilated and contorted portions of the glands being cut in various planes; and (3) next the muscular coat of the uterus a layer containing the contorted but not dilated extremities of the glands is found. Only in the last layer does the epithelium of the glands retain its normal columnar form; elsewhere the cells, separated from the walls of the glands, become enlarged and irregular in shape and eventually degenerate.
In addition to these changes, the epithelium of the mucosa disappears completely during the first month of pregnancy, and the tissue between the glands in the stratum compactum becomes packed with large, often multinucleated cells, which are termed the decidual cells and are probably derived from the connective tissue cells of the mucosa.
After the end of the fifth month the increasing size of the embryo and its membranes exerts a certain amount of pressure on the decidua, and it begins to diminish'in thickness. The portions of the glands which lie in the stratum compactum become more and more compressed and finally disappear, while in the spongiosum the spaces become much flattened and the vascularity of the whole decidua, at first so pronounced, diminishes greatly.
(b) Decidua capsularis.  -  The decidua capsularis has also been termed the decidua reflexa, on the supposition that it was formed as a fold of the uterine mucosa reflected over the ovum after this had
attached itself to the uterine wall. Since, however, the attachment of the ovum is to be regarded as a process of burrowing into the uterine tissues (see p. 119), the necessity for an upgrowth of a fold is limited to an elevation of the uterine tissues in the neighborhood of the ovum to keep pace with its increasing size. Since it is part of the area of contact with the ovum it possesses no epithelium upon the surface turned toward the ovum, although in the earlier stages its surface is covered by an epithelium continuous with that of the decidua vera, and between it and the chorion there is a portion of the blood extravasation in which the villi formed from the chorion laeve float. Glands and blood-vessels also occur in its walls in the earlier stages of development.
As the ovum continues to increase in size the capsularis begins to show signs of degeneration, these appearing first over the pole of the ovum opposite the point of fixation. Here, even in the case of the ovum described by Rossi Doria, the cavity of which measured 6X5 mm. in diameter, it has become reduced to a thin membrane destitute of either blood-vessels or glands, and the degeneration gradually extends throughout the entire capsule, the portion of the blood space which it encloses also disappearing. At about the fifth month the growth of the ovum has brought the capsularis in contact throughout its whole extent with the vera, and it then appears as a whitish transparent membrane with ho trace of either glands or blood-vessels, and it eventually disappears by fusing with the vera.
(c) Decidua basalis.  -  The structure of the decidua basalis, also known as the decidua serotina, is practically the same as that of the vera up to about the fifth month. It differs only in that, being part of the area of contact of the ovum, it loses its epithelium much earlier and is also the seat of extensive blood extravasations, due to the erosion of its vessels by the chorionic trophoblast. Its glands, however, undergo the same changes as those of the vera, so that in it also a compactum and a spongiosum may be recognized. Beyond the fifth month, however, there is a great difference between it and the vera, in that, being concerned with the nutrition of the embryo, it does not partake of the degeneration noticeable in the other deciduae,
but persists until birth, forming a part of the structure termed the placenta.
The Placenta.  -  This organ, which forms the connection between the embryo and the maternal tissues, is composed of two parts, separated by the intervillous space. One of these parts is of embryonic origin, being the chorion frondosum, while the other belongs to the maternal tissues and is the decidua- basalis. Hence the terms placenta fetalis and placenta uterina frequently applied to the two parts. The fully formed placenta is a more or less discoidal structure, convex on the surface next the uterine muscularis and concave on that turned toward the embryo, the umbilical cord being continuous with it near the center of the latter surface. It averages about 3.5 cm. in thickness, thinning out somewhat toward the edges, and has a diameter of 15 to 20 cm., and a weight varying between 500 and 1250 grams. It is situated on one of the surfaces of the uterus, the posterior more frequently than the anterior, and usually much nearer the fundus than the internal orifice. It develops, in fact, wherever the ovum happens to become attached to the uterine walls, and occasionally this attachment is not accomplished until the ovum has descended nearly to the internal orifice, in which case the placenta may completely close this opening and form what is termed a placenta prcevia.
If a section of a placenta in a somewhat advanced stage of development be made, the following structures may be distinguished: On the inner surface there will be a delicate layer representing the amnion (Fig. 79, Am), and next to this a somewhat thicker one which is the chorion (Cho), in which the degenerative changes already mentioned may be observed. Succeeding this comes a much broader area composed of the large intervillous blood space in which lie sections of the villi (vi) cut in various directions. Then follows the stratum compactum of the basalis, next the stratum spongiosum (Z)')> next the outermost layer of the mucosa (D"), in which the uterine glands retain their epithelium, and, finally, the muscularis uteri (Mc)
These various structures have, for the most part, been already
Fig. 79.  -  Section through a Placenta of Seven Months' Development.
Am, Amnion; cho, chorion; D, layer of decidua containing the uterine glands ;(Mc, muscular coat of the uterus; Ve, maternal blood-vessel; Vi, stalk of a villus; vi, villi in section.  -  (Minoi.)
described and it remains here only to say a few words concerning the special structure of the basal compactum and concerning certain changes that take place in the intervillous space.
The stratum compactum of the basal decidua forms what is termed the basal plate of the placenta, closing the intervillous space on the uterine side and being traversed by the maternal blood-vessels that open into the space. The formation of canalized fibrin, already mentioned in connection with the decidua vera and the syncytium of the villi, also occurs in the basal portion of the decidua, a definite layer of it, known as NitabucJi's fibrin stria, being a characteristic constituent of the basal plate and patches of greater or less extent also occur upon the surface of the plate. Leucocytes also occur in considerable abundance in the plate and their presence has been taken to indicate an attempt on the part of the maternal tissues to resist the erosive action of the parasitic ovum. From the surface of the basal plate processes, termed placental septa, project into the intervillous space, grouping the villi into cotyledons and giving attachment to some of the fixation villi (Fig. 80). Throughout the greater extent of the placenta the septa do not reach the surface of the chorion, but at the periphery, throughout a narrow zone, they do come into contact with the chorion and unite beneath it to form a membrane which has been termed the closing plate. Beneath this lies the peripheral portion of the intervillous space, which, owing to the arrangement of the septa in this region, appears to be imperfectly separated from the rest of the space and forms what is termed the marginal sinus (Fig. 80).
Attention has already been called to the formation of canalized fibrin or fibrinoid in connection with the syncytium of the villi. In the later stages of pregnancy there may be produced by this process masses of fibrinoid of considerable size, lying in the intervillous space; these, on account of their color, are termed white infarcts and may frequently be observed as whitish or grayish patches through the walls of the placenta after its expulsion. Red infarcts produced by the clotting of the blood, also occurs, but with much less regularity and frequency.
O <D
O fi ^
h >
§•2 2S
h aft
s a
8 ai ft l
Ch"-" I
« 8 I.
3 "u A
H .5
o -.5
3 ft* â– 
£^ ir! u
£ ••* o
a s rt c S ft
O o-o
.3 8.-°
ft Eo £
03 a n
<C5 a"
PC! „&
CO cj o y
a ^« 3
The Separation of the Deciduae at Birth.  -  At parturition, after the rupture of the amnion and the expulsion of the fetus, there still remain in the uterine cavity the deciduae and the amnion, which is in contact but not fused with the deciduae. A continuance of the uterine contractions, producing what are termed the "after-pains," results in the separation of the placenta from the uterine walls, the separation taking place in the deep layers of the spongiosum, so that the portion of the mucosum which contains the undegenerated glands remains behind. As soon as the placenta has separated, the separation of the decidua vera takes place gradually though rapidly, the line of separation again being in the deeper layers of the stratum spongiosum, and the whole of the deciduae, together with the amnion, is expelled from the uterus, forming what is known as the "after-birth."
Hemorrhage from the uterine vessels during and after the separation of the deciduae is prevented by the contractions of the uterine walls, assisted, according to some authors, by a preliminary blocking of the mouths of the uterine vessels by certain large polynuclear decidual cells found during the later months of pregnancy in the outer layers of the decidua basalis. The regeneration of the uterine mucosa after parturition has its starting-point from the epithelium of the undegenerated glands which persist, this epithelium rapidly evolving a complete mucosa over the entire surface of the uterus.
The complicated arrangement of the human placenta is, of course, the culmination of a long series of specializations, the path along which these have proceeded being probably indicated by the conditions obtaining in some of the lower mammals. The Monotremes resemble the reptiles in being oviparous and in this group of forms there is no relation of the ovum to the maternal tissues such as occurs in the formation of a placenta. In the other mammals viviparity is the rule and this condition does demand some sort of connection between the fetal and maternal tissues. One of the simplest of such connections is that seen in the pig, where the chorionic villi of the ovum fit into corresponding depressions in the uterine mucosa, this tissue, however, undergoing no destruction, and at birth the villi simply withdraw from the depressions of the mucosa, leaving it intact. This type of placentation is an embryo trophic one, and since there is no separation of deciduae from the uterine wall after pregnancy it is also of the indeciduate type. In the sheep the placentation is
also embryotrophic and indeciduate, but destruction of the maternal mucosa does take place, the villi penetrating deeply into it and coming into relation with the connective tissue surrounding the maternal blood-vessels. Another step in advance is shown by the dog, in which even the connective tissue around the maternal vessels in the placental area undergoes almost complete destruction so that the chorionic villi are separated from the maternal blood practically only by the endothelial lining of the maternal vessels. In this case the mucosa undergoes so much alteration that the undestroyed portions if it are sloughed off after birth as a decidua, so that the placentation, like that in man, is of the deciduate type. It still represents, however, an embryotrophic type, although closely approximating to the haemotrophic one found in man, in which, as described above, the destruction of the maternal tissues proceeds so far as to open into the maternal blood-vessels, so that the fetal villi are in direct contact with the maternal blood.
If these various stages may be taken to represent steps by which the conditions obtaining in the human placenta have been evolved, the entire process may be regarded as the result of a progressive activity of a parasitic ovum. In the simplest stage the pabulum supplied by the uterus was sufficient for the nutrition of the parasite, but gradually the ovum, by means of its plasmodi-trophoblast, began to attack the tissues of its host, thus obtaining increased nutrition, until finally, breaking through into the maternal blood-vessels, it achieved for itself still more favorable nutrition, by coming into direct contact with the maternal blood.
In addition to the papers by Beneke and Strahl, Bryce and Teacher, Frassi, Jung, and Herzog, cited in Chapter III, the following may be mentioned:
E. Cova: " Ueber ein menschliches Ei der zweiten Woche," Arch, fur Gynaek., lxxxiii,
1907. L. Frassi: "Ueber ein junges menschliches Ei in situ," Arch, fiir mikr. Anal., lxx,
1907. O. Grosser: "Vergleichende Anatomic und Entwicklungsgeschichte der Eihaute
und der Placenta mit besonderer Berticksichtigung des Menschen," Wien, 1909. H. Happe: "Beobachtungen an Eihauten junger menschlicher Eier," Anat. Hefte,
xxxii, 1906. W. His: "Die Umschliessung der menschlichen Frucht wahrend der friihesten Zeit.
des Schwangerschafts," Archiv fiir Anat. und Physiol., Anat. Abth., 1897. M. Hofmeier: "Die menschliche Placenta," Wiesbaden, 1890.
F. Keibel: "Zur Entwickelungsgeschichte der Placenta," Anat. Anzeiger, iv, 1889.
J. Kollmann: "Die menschlichen Eier von 6 mm. Grosse," Archiv fiir Anat. und Physiol., Anat. Abth., 1879.
G. Leopold: "Ueber ein sehr junges menschliches Ei in situ," Arb. aus der
Frauenklinik in Dresden, rv, 1906.
F. Marchand: "Beobachtungen an jungen menschlichen Eiern," Anat.Hefte, xxi,
1903. J. Merttens: "Beitrage zur normalen und pathologischen Anatomie der mensch
lichen Placenta," Zeitschrift fiir Geburtshiilfe und Gynaekol., xxx and xxxi, 1894. C. S. Minot: "Uterus and Embryo," Journal of Morphol., n, 1889.
G. Paladino: "Sur la genese des espaces intervilleux du placenta humain et de leur
premier contenu, comparativement a la meme partie chez quelques mammiferes,"
Archives Ital. de Biolog., xxxi and xxxn, 1899. H. Peters: "Ueber die Einbettung des menschlichen Eies und das friiheste bisher
bekannte menschliche Placentationsstadium," Leipzig und Wien, 1899. J. Rejsek: "Anheftung (Implantation) des Sangetiereies an die Uteruswand, insbe
sondere des Eies von Spermophilus citellus," Arch, fiir mikrosk. Anat., lxiii, 1964. T. Rossi Doria: "Ueber die Einbettung des menschlichen Eies, studirt an einem
kleinen Eie der zweiten Woche," Arch, fiir Gynaek., lxxvi. 1905. C. Ruge: "Ueber die menschliche Placentation," Zeitschrift fur Geburtshiilfe und
Gynaekol., xxxix, 1898. Siegenbeek van Hetjkelom: "Ueber die menschliche Placentation," Arch. f. Anat.
undPhys., Anat. Abth., 1898. F. Graf Spee: "Ueber die menschliche Eikammer und Decidua reflexa," Verhandl.
des Anat. Gesellsch., xii, 1898. H. Strahl: "Die menschliche Placenta," Ergebn der Anat. und Enlwickl., II, 1893.
"Neues uber den Bau der Placenta," ibid, vi, 1897.
"Placentaranatomie," ibid., viii, 1899. R. Todyo: "Ein junges menschliches Ei," Arch, fiir Gynaek., xcv, 1912. Van Cauwenberghe : "Recherches sur la role du Syncytium dans la nutrition
embryonnaire de la femme," Arch, de Biol., xxiii, 1907. J. C. Webster: "Human Placentation," Chicago, 1901. E. Wormser: "Die Regeneration der Uterusschleimhaut nach der Geburt," Arch.
fiir Gynaek., lxix, 1903.
The Development of the Skin.  -  The skin is composed of two embryologically distinct portions, the outer epidermal layer being developed from the ectoderm, while the dermal layer is mesenchymatous in its origin.
The ectoderm covering the general surface of the body is, in the earliest stages of development, a single layer of cells, but at the end of the first month it is composed of two layers, an outer one, the epitrichium, consisting of slightly flattened cells, and a lower one whose cells are larger and which will give rise to the epidermis (Fig. 81, A). During the second month the differences between the two layers become more pronounced, the epitrichial cells assuming a characteristic domed form and becoming vesicular in structure (Fig. 81, B). These cells persist until about the sixth month of development, but after that they are cast off, and, becoming mixed with the secretion of sebaceous glands which have appeared by this time, form a constituent of the vernix caseosa.
In the meantime changes have been taking place in the epidermal layer which result in its becoming several layers thick (Fig. 81, B), the innermost layer being composed of cells rich in protoplasm, while those of the outer layers are irregular in shape and have clearer contents. As development proceeds the number of layers increases and the superficial ones, undergoing a horny degeneration, give rise to the stratum corneum, while the deeper ones become the stratum
Malpighii. At about the fourth month ridges develop on the under surface of the epidermis, projecting downward into the dermis, and later secondary ridges appear in the intervals between the primary ones, while on the palms and soles ridges appear upon the outer surface of the epidermis, corresponding in position to the primary ridges of the under surface.
The mesenchyme which gives rise to the dermis grows in from all sides between the epidermis and the outer layer of the myotomes,
Fig. 81.  -  A, Section of Skin from the Dorsum of Finger of an Embryo of 4.5 cm.;
B, from the Plantar Surface of the Foot of an Embryo of 10.2 cm
et, Epitrichium; ep, epidermis.
which are at first in contact, and forms a continuous layer underlying the epidermis and showing no indications of a segmental arrangement. It becomes converted "principally into fibrous connective tissue, the outer layers of which are relatively compact, while the deeper ones are looser, forming the subcutaneous areolar tissue. Some of the mesenchymal cells, however, become converted into non-striated muscle-fibers, which for the most part are few in number and associated with the hair follicles, though in certain regions, such as the skin of the scrotum, they are very numerous and
form a distinct layer known as the dartos. Some cells also arrange themselves in groups and undergo a fatty degeneration, well-defined masses of adipose tissue embedded in the lower layers of the dermis being thus formed at about the sixth month.
Although the dermal mesenchyme is unsegmental in character, yet the nerves which send branches to it are segmental, and it might be expected that indications of this condition would be retained by the cutaneous nerves even in the adult. A study of the cutaneous nerve-supply in the adult realizes to a very considerable extent this expectation, the areas supplied by the various nerves forming more or less distinct zones, and being therefore segmental (Fig. 82). But a considerable commingling of adjacent areas has also occurred. Thus, while the distribution of the cutaneous branches of the fourth thoracic nerve, as determined experimentally in the monkey (Macacus), is distinctly zonal or segmental, the nipple lying practically in the middle line of the zone, the upper half of its area is also supplied or overlapped by fibers of the third nerve and the lower half by fibers of the fifth (Fig. 83), so that any area of skin in the zone is innervated by fibers coming from at least two segmental nerves (Sherrington). And, furthermore, the distribution of each nerve crosses the mid-ventral line of the body, forming a more or less extensive crossed overlap.
And not only is there a confusion of adjacent areas but an area may shift its position relatively to the deeper structures supplied by the same nerve, so that the skin over a certain muscle is not necessarily supplied by fibers from the nerve which supplies the muscle. Thus, in the lower half of the abdomen, the skin at any point will be supplied by fibers from higher nerves than those supplying the underlying muscles (Sherrington), and the skin of the limbs may receive twigs from nerves which are not represented at all in the muscle-supply (second and third thoracic and third sacral).
'Ts 7i\
Fig. 82.  -  Diagram showing the cutaneOUS Distribution of the Spinal Nerves -  (Head.)
The Development of the Nails. -  The earliest indications of the development of the nails have been described by Zander in embryos of about nine weeks as slight thickenings of the epidermis
Fig. 83.  -  Diagram showing the Overlap of the III, IV, and V Intercostal Nerves of a Monkey.  -  (Sherrington.)
Fig. 84.  -  Longitudinal Section through the Terminal Joint of the IndexFinger of an Embryo of 4.5 cm. e, Epidermis; ep, epitrichium; nf, nail fold; Ph, terminal phalanx; sp, sole plate.
of the tips of the digits, these thickenings being separated from the neighboring tissue by a faint groove. Later the nail areas migrate to the dorsal surfaces of the terminal phalanges (Fig. 84) and the
grooves surrounding the areas deepen, especially at their proximal edges, where they form the nail-folds (nf) , while distally thickenings of the epidermis occur to form what have been termed sole-plates (sp), structures quite rudimentary in man, but largely developed in the lower animals, in which they form a considerable portion of the claws.
The actual nail substance does not form, however, until the embryo has reached a length of about 17 cm. By this time the epidermis has become several layers thick and its outer layers, over the nail areas as well as elsewhere, have become transformed into the stratum corneum (Fig. 85, sc), and it is in the deep layers of this (the stratum lucidum) that keratin granules develop in cells which degenerate to give rise to the nail substance (n). At its first formation, accordingly, the nail is covered by the outer layers of the stratum corneum as well as by the epitrichium, the two together forming what has been termed the eponychium (Fig. 85, ep). The epitrichium soon disappears, however, leaving only the outer layers of the stratum corneum as a covering, and this also later disappears with the exception of a narrow band surrounding the base of the nail which persists as the perionyx.
The formation of the nail begins in the more proximal portion of the nail area and its further growth is by the addition of new keratinized cells to its proximal edge and lower surface, these cells being formed only in the proximal part of the nail bed in a region marked by its whitish color and termed the lunula.
The first appearance of the nail-areas at the tips of the digits as described by Zander has not yet been
Fig. 85.  -  Longitudinal Section through the nail Area in an Embryo
OF 17 CM.
ep, Eponychium; n, nail substance; nb, nail bed; sc, stratum corneum; sp, sole plate.  -  (Okamura.)
confirmed by later observers, but the migration of the areas to the dorsal surface necessitated by such a location of the primary differentiation affords an explanation of the otherwise anomalous cutaneous nerve-supply of the nail-areas in the adult, this being from the palmar (plantar) nerves.
The Development of the Hairs.  -  The hairs begin to develop at about the third month and continue to be formed during the remaining portions of fetal life. They arise as solid cylindrical downgrowths, projecting obliquely into the subjacent dermis from
to -wl^lvfi
p ...
Fig. 86.  -  The Development of a Hair. c, Cylindrical cells of stratum mucosum; hf, wall of hair follicle; m, mesoderm; mu, stratum mucosum of epidermis; p, hair papilla; r, root of hair; s, sebaceous gland.  -  (Kollmann.)
the lower surface of the epidermis. As these downgrowths continue to elongate, they assume a somewhat club-shaped form (Fig. 86, A), and later the extremity of each club moulds itself over the summit of a small papilla which develops from the dermis (Fig. 86, B). Even before the dermal papilla has made its appearance, however, a
differentiation of the cells of the downgrowth becomes evident, the central cells becoming at first spindle-shaped and then undergoing a keratinization to form the hair shaft, while the more peripheral ones assume a cuboidal form and constitute the lining of the hair follicle. The further growth of the hair takes place by the addition to its basal portion of new keratinized cells, probably produced by the multiplication of the epidermal cells which envelop the papilla.
From the cells which form the lining of each follicle an outgrowth takes place into the surrounding dermis to form a sebaceous gland, which is at first solid and club-shaped, though later it becomes lobed. The central cells of the outgrowth separate from the peripheral and from one another, and, their protoplasm undergoing a fatty degeneration, they finally pass out into the space between the follicle walls and the hair and so reach the surface, the peripheral cells later giving rise by division to new generations of central cells. During fetal life the fatty material thus poured out upon the surface of the body becomes mingled with the cast-off epitrichial cells and constitutes the white oleaginous substance, the vernix caseosa, which covers the surface of the new-born child. The muscles, arrectores pilorum, connected with the hair follicles arise from the mesenchyme cells of the surrounding dermis.
The first growth of hairs forms a dense covering over the entire surface of the fetus, the hairs which compose it being exceedingly fine and silky and constituting what is termed the lanugo. This growth is cast off soon after birth, except over the face, where it is hardly noticeable on account of its extreme fineness and lack of coloration. The coarser hairs which replace it in certain regions of the body probably arise from new follicles, since the formation of follicles takes place throughout the later periods of fetal life and possibly after birth. But even these later formed hairs do not individually persist for any great length of time, but are continually being shed, new or secondary hairs normally developing in their places. The shedding of a hair is preceded by a cessation of the proliferation of the cells covering the dermal papilla and by a shrinkage of the papilla,
whereby it becomes detached from the hair, and the replacing hair arises from a papilla which is probably budded off from the older one before its degeneration and carries with it a cap of epidermal cells.
It is uncertain whether the cases of excessive development of hair over the face and upper part of the body which occasionally occur are due to an excessive development of the later hair follicles (hypertrichosis) or to a persistence and continued growth of the lanugo.
The Development of the Sudoriparous Glands.  -  The sudoriparous glands arise during the fifth month as solid cylindrical outgrowths from the primary ridges of the epidermis (Fig. 87), and at first project vertically downward into the subjacent dermis. Later, however, the lower end of each downgrowth is thrown into coils, and at the same time a lumen appears in the center. Since, however, the cylinders are formed from the deeper layers of the epidermis, their lumina do not at first open upon the surface, but gradually approach it as the cells of the deeper layers of the epidermis replace those which are continually being cast off from the surface of the stratum corneum. The final opening to the surface occurs during the seventh month of development.
The Development of the Mammary Glands.  -  In the majority of the lower mammals a number of mammary glands occur, arranged in two longitudinal rows, and it has been observed that in the pig the first indication of their development is seen in a thickening of the epidermis along a line situated at the junction of the abdominal walls with the membrana reuniens (Schulze). This thickening subsequently becomes a pronounced ridge, the milk ridge, from which, at certain points, the mammary glands develop, the ridge
Fig. 87.  -  Lower Surface of a Detached Portion of Epidermis from the Dorsum of the Hand. h, Hair follicle; s, sudoriparous gland.  -  (Blaschko.)
disappearing in the intervals. In a human embryo 4 mm. in length an epidermal thickening has been observed which extended from just below the axilla to the inguinal region (Fig. 88) and was apparently equivalent to the milk line of the pig, and in embryos of 14 or 15 mm. the upper end of the line had become a pronounced ridge, while more posteriorly the thickening had disappeared.
The further history of the ridge has not, however, been yet traced in human embryos, and the next stage of the development of the glands which has been observed is one in which they are represented by a circular thickening of the epidermis which projects downward into the dermis (Fig. 89, A). Later the thickening becomes lobed (Fig. 89, B), and its superficial and central cells become cornified and are cast off, so that the gland area appears as a depression of the surface of the skin. During the fifth and sixth months the lobes elongate into solid cylindrical columns of cells (Fig. 90) resembling not a little the cylinders which become converted into sudoriparous glands, and each column becomes slightly enlarged at its lower end, from which outgrowths begin to develop to form the acini. A lumen first appears in the lower ends of the columns and is formed by the separation and breaking down of the central cells, the peripheral cells persisting as the lining of the acini and ducts.
The elevation of the gland area above the surface to form the nipple appears to occur at different periods in different embryos and frequently does not take place until after birth. In the region around the nipple sudoriparous and sebaceous glands develop, the latter also occurring within the nipple area and frequently opening into
Fig. 88.  -  Milk Ridge (mr) in a Human Embryo.  -  (Kallius.)
the extremities of the lacteal ducts. In the areola, as the area surrounding the nipple is termed, other glands known as Montgomery' 's glands, also appear, their development resembling that of the mammary gland so closely as to render it probable that they are really rudimentary mammary glands.
" B
Fig. 89.  -  Sections through the Epidermal Thickenings which Represent the Mammary Gland in Embryos (A) of 6 cm. and (B) or 10.2 cm.
The further development of the glands, consisting of an increase in the length of the ducts and the development from them of additional acini, continues slowly up to the time of puberty in both sexes, but at that period further growth ceases in the male, while in females it continues for a time and the subjacent dermal tissues, especially the adipose tissue, undergo a rapid development.
The occurrence of a milk ridge has not yet been observed in a sufficient number of embryos to determine whether it is a normal development or is associated with the formation of supernumerary glands (polymastia). This is by no means an infrequent anomaly; it has been observed in 19 per cent, of over 100,000 soldiers of the German army who were examined, and occurs in 47 per cent, of individuals in certain regions of Germany The extent to which the anomaly is developed varies from the occurrence of well-developed accessory glands to that of rudimentary accessory nipples (Jiy perihelia), these latter sometimes occurring in the areolar area of a normal gland and being possibly due in such cases to an hypertrophy of one or more of Montgomery's glands.
c€; * .-/'-* ., ° '>_,
Fig. 90.  -  Section through the Mammary Gland of an Embryo of 25 cm. 1, Stroma of the gland.  -  (From Nagel, after Basch.)
Although the mammary glands are typically functional only in females in the period immediately succeeding pregnancy, cases are not unknown in which the glands have been well developed and functional in males (gynecomastia). Furthermore, a functional activity of the glands normally occurs immediately after birth, infants of both sexes yielding a few drops of a milky fluid, the so-called witch-milk (Hexenmilch) , when the glands are subjected to pressure.
J. T. Bowen: "The Epitrichial Layer of the Human Epidermis," Anat. Anzeiger, rv
1889. Brouha: •' Recherches sur les diverses phases du developpement et de l'activite dela
mammelle," Arch, de Biol., xxi, 1905. G. Burckhard: "Ueber embryonale Hypermastie und Hyperthelie," Anat. Hefte
viii, 1897. H. Head: "On Disturbances of Sensation with Special Reference to the Pain of
Visceral Disease," Brain, xvi, 1892; xvn, 1894; and xix, 1896. E. Kallius: "Ein Fall von Milchleiste bei einem menschlichen Embryo," Anat.
Hefte, viii, 1897.
T. Okamura: "Ueber die Entwicklung des Nagels beim Menschen," Archiv fur
Dermatol, und Syphilol., xxv, 1900. H. Schmidt: "Ueber normale Hyperthelie menschlicher Embryonen und uber die
erste Anlage der menschlichen Milchdriisen iiberhaupt," Morphol. Arbeiten, xvil,
1897. C. S. Sherrington: "Experiments in Examination of the Peripheral Distribution of
the Fibres of the Posterior Roots of some Spinal Nerves," Philos. Trans. Royal
Soc, clxxxiv, 1893, and cxc, 1898. P. Stohr: " Entwickelungsgeschichte des menschlichen Wollhaares," Anat. Hefte,
xxiii, 1903. H. Strahl: "Die erste Entwicklung der Mammarorgane beim Menschen," Verhandl.
Anat. Gesellsch., xii, 1898.
It has been seen that the cells of a very considerable portion of the somatic and splanchnic mesoderm, as well as of parts of the mesodermic somites, become converted into mesenchyme. A very considerable portion of this becomes converted into what are termed connective or supporting tissues, characterized by consisting of a non-cellular matrix in which more or less scattered cells are embedded. These tissues enter to a greater or less extent into the formation of all the organs of the body, with the exception of those forming the central nervous system, and constitute a network which holds together and supports the elements of which the organs are composed; in addition, they take the form of definite membranes (serous membranes, fasciae), cords (tendons, ligaments), or solid masses (cartilage), or form looser masses or layers of a somewhat spongy texture (areolar tissue). The intermediate substance is somewhat varied in character, being composed sometimes of white, non-branching, non-elastic fibers, sometimes of yellow, branching, elastic fibers, of white, branching, but inelastic fibers which form a reticulum, or of a soft gelatinous substance containing considerable quantities of mucin, as in the tissue which constitutes the Whartonian jelly of the umbilical cord. Again, in cartilage the matrix is compact and homogeneous, or, in other cases, more or less fibrous, passing over into ordinary fibrous tissue, and, finally, in bone the organic matrix is largely impregnated with salts of lime.
Two views exist as to the mode of formation of the matrix, some authors maintaining that in the fibrous tissues it is produced by the actual transformation of the mesenchyme cells into fibers, while others claim that it is manufactured by the cells but does not directly
represent the cells themselves. Fibrils and material out of which fibrils could be formed have undoubtedly been observed in connective-tissue cells, but whether or not these are later passed to the exterior of the cell to form a connective-tissue fiber is not yet certain, and on this hangs mainly the difference between the theories. Recently it has been held (Mall) that the mesenchyme of the embryo is really a syncytium in and from the protoplasm of which the matrix
â– a fmm0m^&
â–  J
Fig. 91.  -  Portion of the Center of Ossification of the Parietal Bone of a
Human Embryo.
forms; if this be correct, the distinction which the older views make between the intercellular and intracellular origin of the matrix becomes of little importance.
Bone differs from the other varieties of connective tissue in that it is never a primary formation, but is always developed either in fibrous tissue or cartilage; and according as it is associated with the one or the other, it is spoken of as membrane bone or cartilage bone. In the development of membrane bone some of the connective-tissue cells, which in consequence become known as osteoblasts, deposit lime salts in the matrix in the form of bony spicules which increase in size and soon unite to form a network (Fig. 91). The trabecular of the network continue to thicken, while, at the same time, the formation of spicules extends further out into the connective-tissue membrane, radiating in all directions from the region in which it first
developed. Later the connective tissue which lies upon either surface of the reticular plate of bone thus produced condenses to form a stout membrane, the periosteum, between which and the osseous plate osteoblasts arrange themselves in a more or less definite layer and deposit upon the surface of the plate a lamella of compact bone. A membrane bone, such as one of the flat bones of the skull, thus comes to be composed of two plates of compact bone, the inner and outer tables, enclosing and united to a middle plate of spongy bone which constitutes the diploe.
With bones formed from cartilage the process is somewhat different. In the center of the cartilage the intercellular matrix becomes increased so that the cells appear to be more scattered and a calcareous deposit forms in it. All around this region of calcification the cells arrange themselves in rows (Fig. 92) and the process of calcification extends into the trabecular of matrix which separate these rows. While these processes have been taking place the mesenchyme surrounding the cartilage has become converted into a periosteum (po), similar to that of membrane bone, and its osteoblasts deposit a layer of bone (p) upon the surface of the cartilage. The cartilage cells now disappear from the intervals between the trabeculae of calcified matrix, which form a fine network into which masses of mesenchyme (Fig. 93, pi), containing blood-vessels and osteoblasts, here and there penetrate from the periosteum, after having broken through the layer of periosteal bone. These masses absorb a portion of the fine calcified network and so transform it
Fig 92.  -  Longitudinal section of Phalanx of a Finger of an Embryo of 3 1/2 Months.
c, Cartilage trabeculae; p, periosteal bone; po, periosteum; x, ossification center.  -  (Szymonowicz.)
C ^ ;
into a coarse network, the meshes of which they occupy to form the bone maigow (m), and the osteoblasts which they contain arrange themselves on the surface of the persisting trabeculse and deposit layers of bone upon their surfaces. In the meantime the calcification of the cartilage matrix has been extending, and as fast as the
network of calcified trabeculse is formed it is invaded by the mesenchyme, until finally the cartilage becomes entirely converted into a mass of spongy bone enclosed within a layer of more compact periosteal bone.
As a rule, each cartilage bone is developed from a single center of ossification, and when it is found that a bone of the skull, for instance, develops by several centers, it is to be regarded as formed by the fusion of several primarily distinct bones, a conclusion which may generally be confirmed by a comparison of the bone in question with its homologues in the lower vertebrates. Exceptions to this rule occur in bones situated in the median line of the body, these occasionally developing from two centers lying one on either side of the median line, but such centers are usually to be regarded as a double center rather than as two distinct centers, and are merely an expression of the fundamental bilaterality which exists even in median structures.
More striking exceptions are to be found in the long bones in which one or both extremities develop from special centers which give rise to the epiphyses (Fig. 94, ep, ep'), the shaft or diaphysis (d) being formed from the primary center. Similar secondary centers appear in marked prominences on bones to which powerful muscles
Fig. 93.  -  The Ossification Center of Fig. 92 More Highly Magnified. c, Ossifying trabeculse; cc, cavity of cartilage network; m, marrow cells; p, periosteal bone; pi, irruption of periosteal tissue; po, periosteum.  -  (Szymonowicz.)
are attached (Fig. 94, a and b), but these, as well as the epiphysial centers, can readily be recognized as secondary from the fact that they do not appear until much later than the primary centers of the bones to which they belong. These secondary centers give the necessary firmness required for articular surfaces and for the attachment of muscles and, at the same time, make provision for the growth in length of the bone, since a plate of cartilage always intervenes between the epiphyses and the diaphysis. This cartilage continues to be transformed into bone on both its surfaces by the extension of both the epiphysial and diaphysial ossification into it, and, at the same time, it grows in thickness with equal rapidity until the bone reaches its required length, whereupon the rapidity of the growth of the cartilage diminishes and it gradually becomes completely ossified, uniting together the epiphysis and diaphysis.
The growth in thickness of the long bones is, however, an entirely different process, and is due to the formation of new layers of periosteal bone on the outside of those already present. But in connection with this process' an absorption of bone also takes place. A section through the middle of the shaft of a humerus, for example, at an early stage of development would show a peripheral zone of compact bone surrounding a core of spongy bone, the meshes of the latter being occupied by the marrow tissue. A similar section of an adult bone, on the other hand, would show only the peripheral compact bone, much thicker than before and enclosing a large marrow cavity in which no trace of spongy bone might remain. The difference depends on the fact that as the periosteal bone
Fig. 94.  -  The Ossification Centers of the Femur.
a, and b, Secondary centers for the great and lesser trochanters; d, diaphysis; ep, upper and ep', lower epiphysis.  -  (Testut.)
increases in thickness, there is a gradual absorption of the spongy bone and also of the earlier layers of periosteal bone, this absorption being carried on by large multinucleated cells, termed osteoclasts, derived from the marrow mesenchyme. By their action the bone is enabled to reach its requisite diameter and strength, without becoming an almost solid and unwieldy mass of compact bone.
During the ossification of the cartilaginous trabeculse osteoblasts become enclosed by the bony substance, the cavities in which they lie forming the lacuna and processes radiating out from them, the
Fig. 95.  -  A, Transverse Section of the Femur of a Pig Killed after Having Been fed with Madder for Four Weeks; B, the Same of a Pig Killed Two Months after the Cessation of the Madder Feeding. The heavy black line represents the portion of bone stained by the madder.  -  (After
canaliculi, so characteristic of bone tissue. In the growth of periosteal bone not only do osteoblasts become enclosed, but bloodvessels also, the Haversian canals being formed in this way, and around these lamellae of bone are deposited by the enclosed osteoblasts to form Haversian systems.
That the absorption of periosteal bone takes place during growth can be demonstrated by taking advantage of the fact that the coloring substance madder, when consumed with food, tinges the bone being formed at the time a distinct red. In pigs fed with madder for a time and then killed a section of the femur shows a superficial band of red bone (Fig. 95, A), but if the animals be allowed to live for one or two months after the cessation of the madder feeding, the red band will be found to be covered by a layer of white bone varying in thickness according to the interval elapsed since the cessation of feeding (Fig. 95, B); and if this
interval amount to four months, it will be found that the thickness of the uncolored bone between the red bone and the marrow cavity will have greatly diminished (Flourens).
The Development of the Skeleton.  -  Embryologically considered, the skeleton is composed of two portions, the axial skeleton, consisting of the skull, the vertebrae, ribs, and sternum, developing
fin* ' \m. :
Fig. 96.  -  Frontal Section through Mesodermic Somites of a Calf Embryo.
isa, Intersegmental artery; my, myotome; n, central nervous system; nc, notochord;
sea and scp, anterior and posterior portions of sclerotomes.
from the sclerotomes of the mesodermal somites, and the appendicular skeleton, which includes the pectoral and pelvic girdles and the bones of the limbs, and which arises from the mesenchyme of the somatic mesoderm. It will be convenient to consider first the development of the axial skeleton, and of this the differentiation of the vertebral column and ribs may first be discussed.
The Development of the Vertebrae and Ribs.  -  The mesenchyme formed from the sclerotome of each mesodermic somite grows inward toward the median line and forms a mass lying between the notochord and the myotome, separated from the similar mass in front and behind by some loose tissue in which lies an intersegmental artery. Toward the end of the third week of
development the cells of the posterior portion of each sclerotome condense to a tissue more compact than that of the anterior portion (Fig. 96), and a little later the two portions become separated by a cleft. At about the same time the posterior portion sends a process medially, to enclose the notochord by uniting with a corresponding process from the sclerotome of the other side, and it also sends a prolongation dorsally between the myotome and the spinal cord to form the vertebral arch, and a third process laterally and ventrally along the distal border of the myotome to form a costal process (Fig. 97). The looser tissue of the anterior half of the sclerotome also grows medially to surround the notochord, filling up the intervals between successive denser portions, and it forms too a membrane extending between successive vertebral arches. Later the tissue surrounding the notochord, which is derived from the anterior half of the sclerotome, associates itself with the posterior portion of the preceding sclerotome to form what will later be a vertebra, the tissue occupying and adjacent to the line of division between the anterior and posterior portions of the sclerotomes condensing to form intervertebral fibrocartilages. Consequently each vertebra is formed by parts
Fig. 97.  -  Transverse Section through the intervertebral plate of the First Cervical Vertebra of a Calf Embryo of 8.8 mm.
be 1 , Intervertebral plate; m i , fourth myotome; s, hypochordal bar; XI, spinal accessory nerve.  -  (Froriep.)
from two sclerotomes, the original intersegmental artery passes over the body of a vertebra, and the vertebrae themselves alternate with the myotomes. With this differentiation the first or blastemic stage of the development of the vertebras closes.
In the second or cartilaginous stage, portions of the sclerotomic mesenchyme become transformed into cartilage. In the posterior portion of each vertebral body, that is to say in the portion formed from the anterior halves of the more posterior of the two pairs of sclerotomes entering into its formation, two centers of chondrification appear, one on each side of the median line, and these eventually unite to form a single cartilaginous body, the chondrification probably also extending to some extent into the denser anterior portion of the body. A center also appears in each half of the vertebral arch and in each costal process, the cartilages formed in the costal processes of the anterior cervical region uniting across the median line below the notochord, to form what has been termed a hypochordal bar (Figs. 97 and 98). These bars are for the most part but transitory, recalling structures occurring in the lower vertebrates; in the mammalia they degenerate before the close of the cartilaginous stage of development, except in the case of the atlas, whose development will be described later. As development proceeds the cartilages of the vertebral arches and costal processes increase in length and come into contact with the cartilaginous bodies, with which they eventually fuse, and from the vertebral arches processes grow out which represent the future transverse and articular processes.
The fusion of the cartilage of the costal process with the body of the vertebra does not, however, persist. Later a solution of the junction occurs and the process becomes a rib cartilage, the mesenchyme surrounding the area of solution forming the costo-vertebral ligaments. At first the rib cartilage is separated by a distinct interval from the transverse process of the vertebral arch, but later it develops a process, the tubercle, which bridges the gap and forms an articulation with the transverse process.
The mesenchyme which extends between successive vertebral arches does not chondrify, but later becomes transformed into the
interspinous ligaments and the ligamenta ftava, while the anterior and posterior longitudinal ligaments are formed from unchondrified portions of the tissue surrounding the vertebral bodies.
As was pointed out, the mesenchyme in the region of the cleft separating the anterior and posterior portions of a sclerotome becomes an intervertebral fibrocartilage, and, as the cartilaginous bodies develop, the portions of the notochord enclosed by them become constricted, while at the same time the portions in the intervertebral regions increase in size. Finally the notochord disappears from the vertebral regions, although a canal, representing its former position, traverses each body for a considerable time, but in the intervertebral regions it persists as relatively large flat disks forming the pulpy nuclei of the fibrocartilages.
The mode of development described above applies to the great majority of the vertebrae, but some departures from it occur, and these may be conveniently considered before passing on to an account of the ossification of the cartilages. The variations affect principally the extremes of the series. Thus the posterior vertebrae present a reduction of the vertebral arches, those of the last sacral vertebrae being but feebly developed, while in the coccygeal vertebrae they are indicated only in the first. In the first cervical vertebra, the atlas, the reverse is the case, for the entire adult vertebra is formed from the posterior portion of a sclerotome, its lateral masses and posterior arch being the vertebral arches, while its anterior arch is the hypochordal bar, which persists in this vertebra only. A welldeveloped centrum is also formed, however (Fig. 98), but it does not unite with the parts derived from the preceding sclerotome, but during its ossification unites with the centrum of the epistropheus (axis), forming the odontoid process of that vertebra. The epistropheus consequently is formed by one and a half sclerotomes, while but half a one constitutes the atlas.
The extent to which the ribs are developed in connection with the various vertebrae also varies considerably. Throughout the cervical region they are short, the upper five or six being no longer than the transverse processes, with the tips of which their extremities
unite at an early stage. In the upper five or six vertebrae a relatively large interval persists between the rib and the transverse process, forming the costo-transverse foramen, through which the vertebral vessels pass, but in the seventh vertebra the fusion is more extensive and the foramen is very small and hardly noticeable. In the thoracic region the ribs reach their greatest development, the upper eight or
â–  \;-^Z ... --â– 
Fig. 9,8.  -  Longitudinal Section through the Occipital Region and Upper
Cervical Vertebrae of a Calf Embryo of 18.5 mm.
has, Basilar artery; ch, notochord; Kc l ~ 4 , vertebral centra; lc 2 ~ 4 , intervertebral
disks; occ, basioccipital; Sc x ~ 4 , hypochordal bars.  -  (Froriep.)
nine extending almost to the mid-ventral line, where their extremities unite to form a longitudinal cartilaginous bar from which the sternum develops (see p. 166). The lower three or four thoracic ribs are successively shorter, however, and lead to the condition found in the lumbar vertebras, where they are again greatly reduced and firmly united with the transverse processes, the union being so close that only the tips of the latter can be distinguished, forming what are known as the accessory tubercles. In the sacral region the ribs
are reduced to short flat plates, which unite together to form the lateral masses of the sacrum, and, finally, in the coccygeal region the blastemic costal processes of the first vertebra unite with the transverse processes to form the transverse processes of the adult vertebra, but no indications of them are to be found in the other vertebrae beyond the blastemic stage.
The third stage in the development of the axial skeleton begins with the ossification of the cartilages, and in each vertebra there are typically as many primary centers of ossification as there were originally cartilages, except that but a single center appears in the body. Thus, to take a thoracic vertebra as a type, a center appears in each half of each vertebral arch at the base of the transverse process and gradually extends to form the bony lamina, pedicle, and the greater portion of the transverse and spinous processes; a single center gives rise to the body of the vertebra; and each rib ossifies
Fig. 99.  -  A, A Vertebra at Birth; B, Lumbar Vertebra showing Secondary Centers of Ossification. a, Center for the articular process; c, body; el, lower epiphysial plate; en, upper epiphysial plate; na, vertebral arch; s, center for spinous process; t, center for transverse process.  -  (Sappey.)
from a single center. These various centers appear early in embryonic life, but the complete transformation of the cartilages into bone does not occur until some time after birth, each vertebra at that period consisting of three parts, a body and two halves of an arch, separated by unossified cartilage (Fig. 99, A). At about puberty secondary centers make their appearance; one appears in the cartilage which still covers the anterior and posterior surfaces of the vertebral body, producing disks of bone in these situations (Fig. 99,
l6 5
B, en and el), another appears at the tip of each spinous and transverse process (Fig. 99, B), and in the lumbar vertebrae others appear at the tips of the articulating processes. The epiphyses so formed remain separate until growth is completed and between the sixteenth and twenty-fifth years unite with the bones formed from the primary centers, which have fused by this time, to form a single vertebra.
Each rib ossifies from a single primary center situated near the angle, secondary centers appearing for the capitulum and tuberosity.
In some of the vertebras modifications of this typical mode of ossification occur. Thus, in the upper five cervical vertebrae the centers for the rudimentary ribs are suppressed, ossification extending into them from the vertebral arch centers, and a similar suppression of the costal centers occurs in the lower lumbar vertebrae, the first only developing a separate rib center. Furthermore, in the
Fig. ioo. - A, Upper Surface of the First Sacral Vertebra, and B, Ventral
View of the Sacrum showing Primary Centers of Ossification.
c, Body; na, vertebral arch; r, rib center.  -  (Sappey.)
atlas a double center appears in the persisting hypochordal bar, and the body which corresponds to the atlas, after developing the terminal epiphysial disks, fuses with the body of the epistropheus (axis) to form its odontoid process, this vertebra consequently possessing, in addition to the typical centers, one (double) other primary and two secondary centers. In the sacral region the typical centers appear
in all five vertebrae, with the exception of rib centers for the last one or two (Fig. ioo) and two additional secondary centers give rise to plate-like epiphyses on each side, the upper plates forming the articular surface for the ilium. At about the twenty-fifth year all the sacral vertebrae unite to form a single bone, and a similar fusion occurs also in the rudimentary vertebrae of the coccyx.
The majority of the anomalies seen in the vertebral column are due to the imperfect development of one or more cartilages or of the centers of ossification. Thus, a failure of an arch to unite with the body or even the complete absence of an arch or half an arch may occur, and in cases of spina bifida the two halves of the arches fail to unite dorsally. Occasionally the two parts of the double cartilaginous center for the body fail to unite, a double body resulting; or one of the two parts may entirely fail, the result being the formation of only one-half of the body of the vertebra. Other anomalies result from the excessive development of parts. Thus, the rib of the seventh cervical vertebra may sometimes remain distinct and be long enough to reach the sternum, and the first lumbar rib may also fail to unite with Its vertebra. On the other hand, the first thoracic rib is occasionally found to be imperfect.
The Development of the Sternum.  -  Longitudinal bars, which are formed by the fusion of the ventral ends of the anterior eight or nine cartilaginous thoracic ribs, represent the future sternum. At an early period the two bars come into contact anteriorly and fuse together (Fig. 101), and at this anterior end two usually indistinctly separated masses of cartilage are to be observed at the vicinity of the points where the ventral ends of the cartilaginous clavicles articulate. These are the episternal cartilages (em), which later normally unite with the longitudinal bars and form part of the manubrium sterni, though occasionally they persist and ossify to form the ossa suprasternal. The fusion of the longitudinal bars gradually extends backward until a single elongated plate of cartilage results, with which the seven anterior ribs are united, one or two of the more posterior ribs which originally took part in the formation of each bar having separated. The portions of the bars formed by these posterior ribs constitute the xiphoid process.
The ossification of the sternum (Fig. 102) partakes to a certain extent of the original bilateral segmental origin of the cartilage,
but there is a marked condensation of the centers of ossification and considerable variation in their number also occurs. In the portion of the cartilage which lies below the junction of the third costal cartilages a series of pairs of centers appears just about birth, each center
Fig. ioi.  -  Formation of the Sternum in an Embryo of About 3 cm. el, Clavicle; em, episternal cartilage.  -  (Ruge.)
probably representing an epiphysial center of a corresponding rib. Later the centers of each pair fuse and the single centers so formed, extending through the cartilage, eventually unite to form the greater part of the body of the bone. In each of the two uppermost segments, however, but a single center appears, that of the second segment uniting with the more posterior centers and forming the upper part of the body, while the uppermost center gives rise to the manubrium, which frequently persists as a distinct bone united to the body by a hinge-joint.
A failure of the cartilaginous bars to fuse produces the condition known as cleft sternum, or if the failure to fuse affects only a portion of the bars there results a perforated sternum. A perforation or notching of the xiphoid cartilage is of frequent occurrence owing to this being the region where the fusion of the bars takes place last.
Fig. i 02.  -  Sternum of New-born Child, showing Centers of Ossification. I to VII, Costal cartilages.  -  (Gegenbaur.)
Fig. 103.  -  Reconstruction of the Chondrocranium of an embryo of 14 mm. as, Alisphenoid; bo, basioccipital; bs, basisphenoid; eo, exoccipital; m, Meckel's cartilage; os, orbitosphenoid; p, periotic; ps, presphenoid; so, sella turcica; s, supraoccipital.  -  (Levi.)
The suprasternal bones are the rudiments of a bone or cartilage, the omosternum, situated in front of the manubrium in many of the lower mammalia. It furnishes the articular surfaces for the clavicles and is possibly formed by a fusion of the ventral ends of the cartilages which represent those bones; hence its appearance as a pair of bones in the rudimentary condition.
The Development of the Skull.  -  In its earliest stages the human skull is represented by a continuous mass of mesenchyme which invests the anterior portion of the notochord and extends forward beyond its extremity into the nasal region, forming a core for the nasal process (see p. 99). From each side of this basal mass a wing projects dorsally to enclose the anterior portion of the medullary canal which will later become the cerebral part of the central nervous system. No indications of a segmental origin are to be
found in this mesenchyme; as stated, it is a continuous mass, and this is likewise true of the cartilage which later develops in it.
The chondrihcation occurs first along the median line in what will be the occipital and sphenoidal regions of the skull (Fig. 103) and thence gradually extends forward into the ethmoidal region and to a certain extent dorsally at the sides and behind into the regions later occupied by the wings of the sphenoid (as and os) and the squamous portion of the occipital (s). No cartilage develops, however, in the rest of the sides or in the roof of the skull, but the mesenchyme of these regions becomes converted into a dense membrane of connective tissue. While the chondrification is proceeding in the regions mentioned, the mesenchyme which encloses the internal ear becomes converted into cartilage, forming a mass, the periotic capsule (Fig. 103, p), wedged in on either side between the occipital and sphenoidal regions, with which it eventually unites to form a continuous chondro cranium, perforated by foramina for the passage of nerves and vessels.
The posterior part of the basilar portion of the occipital cartilage presents certain peculiarities of development. In calf embryos there are in this region, in very early stages, four separate condensations of mesoderm corresponding to as many mesodermic somites and to the three roots of the hypoglossal nerve together with the first cervical or suboccipital nerve (Froriep) (Fig. 104). These mesenchymal masses in their general characters and relations resemble vertebral bodies, and there are good reasons for believing that they represent four vertebrae which, in later stages, are taken up into the skull region and fuse with the primitive chondrocranium. In the human embfyo they are less distinct than in lower mammals, but since a three-rooted hypoglossal and a suboccipital nerve also occur in man it is probable that the corresponding vertebrae are also represented. Indeed, confirmation of their existence may be found in the fact that during the cartilaginous stage of the skull the hypoglossal foramina are divided into three portions by two cartilaginous partitions which separate the three roots of the hypoglossal nerve. It seems certain from the evidence derived from embryology and comparative
anatomy that the human skull is composed of a primitive unsegmental chondrocranium plus four vertebrae, the latter being added
to and incorporated with the occipital portion of the chondrocranium. Emphasis must be laid upon the fact that the cartilaginous portion of the skull forms only the base and lower portions of the sides of the cranium, its entire roof, as well as the face region, showing no indication of cartilage, the mesenchyme in these regions being converted into fibrous connective tissue, which, especially in the cranial region, assumes the form of a dense membrane.
But in addition to the chondrocranium and the vertebras incorporated with it, other cartilaginous elements enter into the composition of the skull. The mesenchyme which occupies the axis of each branchial arch undergoes more or less complete chondrification, cartilaginous bars being so formed, certain of which enter into very close relations with the skull. It has been seen (p. 92) that each half of the first arch gives rise to a maxillary process which grows forward and ventrally to form the anterior boundary of the mouth, while the remaining portion of the arch forms the mandibular process. The whole of the axis of the mandib
J-^V : y:
Fig. 104.  -  Frontal Section through the occipital and upper Cervical Regions of a Calf Embryo of 8.7 MM.
ai and ai 1 , Intervertebral arteries; be 1 , first cervical intervertebral plate; bo, suboccipital intervertebral plate; c 1 -  2 , cervical nerves; eh, notochord; K, vertebral centrum; m l  -  3 , occipital myotomes; m 4 -  5 , cervical myotomes; 1 -  3 , roots of hypoglossal nerve; vj, jugular vein; x and xi, vagus and spinal accessory nerves.  -  (Froriep.)
ular process becomes chondrified, forming a rod known as Meckel's cartilage, and this, at its dorsal end, comes into relation with the periotic capsule, as does also the dorsal end of the cartilage of the second arch. In the remaining three arches cartilage forms only in the ventral portions, so that their rods do not come into relation with the skull, though it will be convenient to consider their further history together with that of the other branchial arch cartilages. The arrangement of these cartilages is shown diagrammatically in Fig. 105.
By the ossification of these various parts three categories of bones are formed: (1) cartilage bones formed in the chondrocranium, (2) membrane bones, and (3) cartilage bones developing from the cartilages of the branchial arches. The bones belonging to each of these categories are primarily quite distinct from one another and from those of the other groups, but in the human skull a very considerable amount of fusion of the primary bones takes place, and elements belonging to two or even to all three categories may unite to form a single bone of the adult skull. In a certain region of the chondrocranium also and in one of the branchial arches the original cartilage bone becomes ensheathed by membrane bone and eventually disappears completely, so that the adult bone, although represented by a cartilage, is really a membrane bone. And, indeed, this process has proceeded so far in certain portions of the branchial arch skeleton that the original cartilaginous representatives are no longer developed, but the bones are deposited directly in connective tissue. These various modifications interfere greatly with the precise application to the human skull of the classification of bones into the three categories given above, and indeed the true significance of certain of the skull bones can only be perceived by comparative
Fig. 105.  -  Diagram showing the Five
Branchial Cartilages, I to'F.
At, Atlas; Ax, epistropheus; 3, third
cervical vertebra.
studies. Nevertheless it seems advisable to retain the classification, indicating, where necessary, the confusion of bones of the various categories.
The Ossification of the Chondrocranium.  -  The ossification of the cartilage of the occipital region results in the formation of four distinct bones which even at birth are separated from one
another by bands of cartilage. The portion of cartilage lying in front of the foramen magnum ossifies to form a basioccipital bone (Fig. 106, bo), the portions on either side of this give rise to the two exoccipitals (eo), which bear the condyles, and the portion above the foramen produces a supraoccipital (so), which represents the part of the squamous portion of the adult bone lying below the superior nuchal line. All that portion of the bone which lies above that line is composed of membrane bone which owes its origin to the fusion of two or sometimes four centers of ossification, appearing in the membranous roof of the embryonic skull. The bone so formed (ip) represents the interparietal of lower vertebrates and, at an early stage, unites with the supraoccipital, although even at birth an indication of the line of union of the two parts is to be seen in two deep incisions at the sides of the bone. The union of the exoccipitals and supraoccipital takes place in the course of the first or second year after birth, but the basioccipital does not fuse with the rest of the bone until the sixth or eighth year. It will be noticed that no special centers occur for the four occipital vertebrae, these structures having become completely incorporated in the chondro
Fig. 106.  -  Occipital Bone of a Fetus
at Term. bo, Basioccipital; eo, exoccipital; ip, interparietal; so, supraoccipital.
cranium, and even the cartilaginous partitions which divide the hypoglossal foramina usually disappear during the process of ossification.
Two pairs of centers have been described for the interparietal bone and it has been claimed that the deep lateral incisions divide the lower pair, so that when the incisions meet and persist as the sutura mendosa, separating the so-called inca bone from the rest of the occipital, the division does not correspond to the line between the supraoccipital and the interparietal, but a portion of the latter bone remains in connection with the supraoccipital. Mall, however, in twenty preparations, found but a single pair of centers for the interparietal.
Occasionally an additional pair of small centers appear for the uppermost angle of the interparietal, and the bones formed from them may remain distinct as what have been termed fontanelle bones.
Fig. 107.  -  Sphenoid Bone from Embryo of 3^ to 4 Months. The parts which are still cartilaginous are represented in black, as, Alisphenoid ; b, basisphenoid; /, lingula; os, orbitosphenoid ; p, internal pterygoid plate.  -  (Sappey.)
In the sphenoidal region the number of distinct bones which develop is much greater than in the occipital region. At the beginning of the second month a center appears in each of the cartilages which represent the alisphenoids (great wings). These cartilages do not, however, represent the entire extent of the great wings and their ossification gives rise only to those portions of the bone in the neighborhood of the foramina ovale and rotundum and to the lateral pterygoid plates. The remaining portions of the wings, the orbital and temporal portions, develop as membrane bone (Fawcett)
and early unite with the portions formed from the cartilage. At the end of the second month a center appears in each orbito sphenoid (lesser wing) cartilage (Fig. 107, os), and a little later a pair of centers (b), placed side by side, are developed in the cartilage representing the posterior portion of the body; together these form what is known as the basisphenoid. Still later a center appears on either side of the basisphenoids to form the UngulcB (I), and another pair appears in the anterior part of the cartilage, between the orbitosphenoids, and represent the presphenoid.
In addition to these ten centers in cartilage and the membrane portion of the alisphenoid, two other membrane bones are included in the adult sphenoid. Thus, a little before the appearance of the center for the alisphenoids an ossification is formed in the mesenchyme of each lateral wall of the posterior part of the nasal cavity and gives rise to the medial lamina of the pterygoid process, the mesenchyme at the tip of the ossification condensing to form a cartilaginous hook-like structure over which the tendon of the tensor veli palatini plays. This cartilage later ossifies to form the pterygoid hamulus, the medial pterygoid lamina being thus a combination of membrane and cartilage, the latter, however, being a secondary development and quite independent of the chondrocranium.
By the sixth month the lingular have fused with the basisphenoid and the orbitosphenoids with the presphenoid, and a little later the basisphenoid and presphenoid unite. The alisphenoids and medial pterygoid laminae remain separate, however, until after birth, fusing with the remaining portions of the adult bone during the first year.
The cartilage of the ethmoidal region of the chondrocranium forms somewhat later than the other portions and consists at first of a stout median mass projecting downward and forward into the nasal process (Fig. 108, Ip), and two lateral masses (lm), situated one on either side in the mesenchyme on the outer side of each olfactory pit. Ossification of the lateral masses or ectethmoids begins relatively early, but it appears in the upper part of the median cartilage only after birth, producing the crista galli and the perpendicular plate, which together form what is termed the mesethmoid. When
first formed, the three cartilages are quite separate from one another, the olfactory and nasal nerves passing down between them to the olfactory pit, but later trabecular begin to extend across from the mesethmoid to the upper part of the ectethmoids and eventually form a fenestrated horizontal lamella which ossifies to form the cribriform plate.
The lower part of the median cartilage does not ossify, but a center appears on each side of the median line in the mesenchyme behind and below its posterior or lower border. From these centers two vertical bony plates develop which unite by their median surfaces below, and above invest the lower border of the cartilage and form the vomer. The portion of the cartilage which is thus invested undergoes resorption, but the more anterior portions persist to form the cartilaginous septum of the nose. The vomer, consequently, is not really a portion of the chondrocranium, but is a membrane bone; its intimate relations with the median ethmoidal cartilage, however, make it convenient to consider it in this place.
When first formed, the ectethmoids are masses of spongy bone and show no indication of the honeycombed appearance which they present in the adult skull. This condition is produced by the absorption of the bone of each mass by evaginations into it of the mucous membrane lining the nasal cavity. This same process also brings about the formation of the curved plates of bone which project from the inner surfaces of the lateral masses and are known as the superior and middle conchse (turbinated bones). The inferior and sphenoidal conchae are developed from special centers, but belong to the same category as the others, being formed from portions of the lateral ethmoidal cartilages which become almost
Fig. 108.  -  Anterior Portion of the Base of the Skull of a 6 to 7 Months' Embryo.
The shaded parts represent cartilage. cp, Cribriform plate; hn, lateral mass of the ethmoid; Ip, perpendicular plate; of optic foramen; os, orbitosphenoid.  -  (After von Spec.)
separated at an early stage before the ossification has made much progress. Absorption of the body of the sphenoid bone to form the sphenoidal cells, of the frontal to form the frontal sinuses, and of the maxillaries to form the maxillary antra is also produced by outgrowths of the nasal mucous membrane, all these cavities, as well as the ethmoidal cells, being continuous with the nasal cavities and lined with an epithelium which is continuous with the mucous membrane of the nose.
In the lower mammalia the erosion of the mesial surface of the ectethmoidal cartilages results, as a rule, in the formation of five conchae, while in man but three are usually recognized. Not infrequently, however, the human middle concha shows indications, more or less marked, of a division into an upper and a lower portion, which correspond to the third and fourth bones of the typical mammalian arrangement. Furthermore, at the upper portion of the nasal wall, in front of
the superior concha, a slight elevation, termed the agger nasi, is always observable, its lower edge being prolonged downward to form what is termed the uncinate process of the ethmoid. This process and the agger together represent the uppermost concha of the typical arrangement, to which, therefore, the human arrangement may be reduced.
A number of centers of ossification  -  the exact number is yet uncertain  -  appear in the periotic capsule during the later portions of the fifth month, and during the sixth month these unite together to form a single center from which the complete ossification of the cartilage proceeds to form the petrous and mastoid portions of the temporal bone (Fig. 109, p). The mastoid process does not really form until several years after birth, being produced by the hollowing and bulging out of a portion of the petrous bone by out-growths from the lining membrane of the middle ear. The cavities so formed are the mastoid cells, and their relations to the middle-ear cavity are in all respects similar to those of the ethmoidal
Fig. 109.  -  The Temporal
Bone at Birth. The Styloid
Process and Auditory Ossicles
are not Represented.
p, Petrous bone; s, squamosal;
t, tympanic.  -  (Poirier.)
and sphenoidal cells to the nasal cavities. The remaining portions of the temporal bone are partly formed by membrane bone and partly from the branchial arch skeleton. An ossification appears at the close of the eighth week in the membrane which forms the side of the skull in the temporal region and gives rise to a squamosal bone (s), which later unites with the petrous to form the squamosal portion of the adult temporal, and another membrane bone, the tympanic (/), develops from a center appearing in the mesenchyme surrounding the external auditory meatus, and later also fuses with the petrous to form the floor and sides of the external meatus, giving attachment at its inner edge to the tympanic membrane. Finally, the styloid process is developed from the upper part of the second branchial arch, whose history will be considered later.
The various ossifications which form in the chondrocranium and the portions of the adult skull which represent them are shown in the following table:
Region of Chondrocranium.
IBasioccipital Exoccipitals Supraoccipital
Ethmoidal .
Parts of Adult Skull;
Basilar process. Condyles.
Squamous portion below superior nuchal line.
Greater wings (in part) . Lesser wings. Lamina perpendicularis. Crista galli. Nasal septum. Lateral masses. Superior concha. Middle concha.
Inferior concha.
Sphenoidal concha.
,, . . f Mastoid.
Penolic capsule < _.
1 Petrous.
The Membrane Bones of the Skull. -  In the membrane forming the sides and roof of the skull in the second stage of its develop
ment ossifications appear, which give rise, in addition to the interparietal and squamosal bones already mentioned in connection with the occipital and temporal, to the parietals and frontal. Each of the former bones develops from a single center which appears at the end of the eighth week, while the frontal is formed at about the same time from two centers situated symmetrically on each side of the median line and eventually fusing completely to form a single bone, although more or less distinct indications of a median suture, the metopic, are not infrequently present.
Furthermore, ossifications appear in the mesenchyme of the facial region to form the nasal, lachrymal, and zygomatic bones, all of which arise from single centers of ossification. In the case of each zygomatic bone, however, three osseous thickenings appear on the inner surface of the original ossification, which then disappears and the thickenings unite to form the adult bone, though occasionally one or more of their lines of union may persist, producing a bipartite or tripartite zygomatic.
The vomer, which has already been described, belongs also strictly to the category of membrane bones, as do also the maxillae and the palatines; these latter, however, primarily belonging to the branchial arch skeleton, with which they will be considered.
The purely membrane bones in the skull, are, then, the following:
Interparietals Part of squamous portion of occipital.
Pterygoids Medial pterygoid plates.
Squamosals Squamous portions of temporals.
Tympanies Tympanic plates of temporals.
The Ossification of the Branchial Arch Skeleton.  -  It has
been seen (p. 171) that a cartilaginous bar develops only in the mandibular process of the first branchial arch. In the maxillary process no cartilaginous skeleton forms, but two membrane bones,
Fig. i 10.  -  Diagram of the Ossifications of which the Maxilla is Composed, as seen from the Outer Surface. The Arrow Passes through the Infraorbital Canal.  -  (From von Spee, after Sappey.)
the palatine and maxilla, are developed in it, their cartilaginous representatives, which are to be found in lower vertebrates, having been suppressed by a condensation of the development. The palatine bone develops from a single center of ossification, but for each maxilla no less than five centers have been described (Fig. no). One of these gives rise to so much of the alveolar border of the bone as contains the bicuspid and molar teeth; a second forms the nasal process and the part of the alveolar border which contains the canine tooth; a third the portion which contains the incisor teeth; while the fourth and fifth centers lie above the first and give rise to the inner and outer portions of the orbital plate and the body of the bone. The first, second, fourth, and fifth portions early unite together, but the third center, which really lies in the ventral part of the nasal process, remains separate for some time, forming what is termed the premaxilla, a bone which remains permanently distinct in the majority of the lower mammals.
The above is the generally accepted view as to the development of the maxilla. Mall, however, maintains^ that it has but tw r o centers of ossification, one giving rise to the premaxilla and the other to the rest of the bone. The maxillary center makes its appearance about the middle of the sixth week.
Since the condition known as hare-lip results from a failure of the maxillary process to unite completely with the frontonasal process (see p. 100), and since the premaxilla develops in the latter and the maxilla in the former, the cleft may pass between these two bones and prevent their union (see also p. 284).
The upper end of Meckel's cartilage passes between the tympanic bone and the outer surface of the periotic capsule and thus comes to lie apparently within the tympanic cavity of the ear; this portion of the cartilage divides into two parts which ossify to form two of the bones of the middle ear, the malleus and incus, a description of
whose further development may be postponed until a later chapter. At about the middle of the sixth week of development a plate of membrane bone appears to the outer side of the lower portion of the cartilage and gradually extends to form the body and ramus of the mandible.
In the region of the body the bone develops so as to enclose the cartilage, together with the inferior alveolar (dental) nerve which lies to the outer side of the cartilage, but in the region of the ramus
Fig. hi. -  Model of Right Half of Mandible of a Fetus 95 mm. in Length, seen from the mesial surface. C 1 and C 2 , Accessory cartilages; Ch. T., chorda tympanijO., cartilage for coronoid process; Cy., cartilage for condyloid process; Mai., malleus; M.C., Meckel's cartilage; N. Al., inferior alveolar nerve; N. Aur., auriculo-temporal nerve; N.L., lingual nerve; N.Mh., mylo-hyoid nerve; N.T., trigeminal nerve; Sy., symphysis.  -  (Low.)
the bone remains entirely to the outer side of the cartilage and nerve, whence the position of the mandibular foramen on the inner surface of the adult bone. The anterior portion of Meckel's cartilage becomes ossified by the extension of ossification from the membrane bone into it, the portion corresponding to the body of the bone behind the mental foramen disappears and the portion above the mandibular foramen is said to become transformed into fibrous connective tissue and to persist as the spheno-mandibular ligament. At the upper extremity of the ramus two nodules of cartilage develop, quite independently, however, of Meckel's cartilage (Fig. in, Cr and Cy),
and ossification extends into these from the ramus to form the coronoid and condyloid processes. And, finally, two other independent cartilages appear toward the anterior extremity of each half
Fig. 112.  -  Diagram showing the Categories to which the Bones of the Skull . . Belong.
The unshaded bones are membrane bones, the heavily shaded represent the chondrocranium, while the black represents the branchial arch elements. AS, Alisphenoid; ExO, exoccipital; F, frontal; Hy, hyoid; IP, interparietal; Z, zygomatic; Mn, mandible; Mx, maxilla; NA, nasal; P, parietal; Pe, periotic; SO, supraoccipital; Sg, squamosal; St, styloid process; Th, thyreoid cartilage; Ty, tympanic.
of the bone, one at the alveolar (C t ) and the other at the lower border (C 2 ), and these, also are later incorporated into the bone without developing special centers of ossification.
Each half of the mandible thus ossifies from a single center, and is essentially a membrane bone replacing a cartilaginous precursor. At birth the two halves are united at the symphysis by fibrous tissue, into which ossification extends later, union occurring in the first or second year.
The upper part of the cartilage of the second branchial arch also comes into relation with the tympanic cavity and ossifies to form the styloid process of the temporal bone. The succeeding moiety of the cartilage undergoes degeneration to form the stylo-hyoid ligament, while its most ventral portion ossifies as the lesser comu of trie hyoid bone. The great variability which may be observed in the length of the styloid processes and of the lesser cornua of the hyoid depends upon the extent to which the ossification of the original cartilage proceeds, the length of the stylo-hyoid ligaments being in inverse ratio to the length of the processes or cornua. The greater cornua of the hyoid are formed by the ossification of the cartilages of the third arch, and the body of the bone is formed from a cartilaginous plate, the copula, which unites the ventral ends of the two arches concerned.
Finally, the cartilages of the fourth and fifth branchial arches early fuse together to form a plate of cartilage, and the two plates of opposite sides unite by their ventral edges to form the thyreoid cartilage of the larynx.
The accompanying diagram (Fig. 112) shows the various structures derived from the branchial arch skeleton, as well as some of the other elements of the skull, and a re'sume' of the fate of the branchial arches may be stated in tabular form as follows, the parts represented by cartilage which becomes replaced by membrane bone being printed in italics, while membrane bones which have no cartilaginous representatives are enclosed in brackets:
(Palatine) .
Spheno-mandibular ligament.
1st arch.
(Styloid process of the temporal. Stylo-hyoid ligament. Lesser cornu of hyoi< 1 .
3d arch Greater cornu of hyoid.
4th and 5th arches Thyreoid cartilage of larynx.
The Development of the Appendicular Skeleton.  -  While the greater portion of the axial skeleton is formed from the sclerotomes of the mesodermic somites, the appendicular skeleton is derived from the somatic mesenchyme, which is not divided into metameres. This mesenchyme forms the core of the limb bud and becomes converted into cartilage, by the ossification of which all the bones of the limbs, with the possible exception of the clavicle, are formed.
Of the bones of the pectoral girdle the clavicle requires further study before it can be certain whether it is to be regarded as a purely cartilage bone or as a combination of cartilage and membrane ossification (Gegenbaur). It is the first bone of the skeleton to ossify, two centers appearing for each bone at about the sixth week of development. The tissue in which the ossifications form has certain peculiar characters, and it is difficult to say whether it is to be regarded as cartilage which, on account of the early differentiation of the center, has not yet become thoroughly differentiated histologically, or as some other form of connective tissue. However that may be, true cartilage develops on either side of the ossifying region, and into this the ossification gradually extends, so that at least a portion of the bone is preformed in cartilage.
The scapula is at first a single plate of cartilage in which two centers of ossification appear. One of these gives rise to the body and the spine, while the other produces the coracoid process (Fig. 113, co), the rudimentary representative of the coracoid bone which extends between the scapula and sternum in the lower vertebrates. The coracoid does not unite with the body until about the fifteenth year, and secondary centers which give rise to the vertebral edge (b) and inferior angle of the bone (a) and to the acromion process (c) unite with the rest of the bone at about the twentieth year.
1 84
The humerus and the bones of the forearm are typical long bones, each of which develops from a primary center, which gives rise to the shaft, and has, in addition, two or more epiphysial centers. In the humerus an epiphysial center appears for the head, another for the greater tuberosity, and usually a third for the lesser tuberosity, while at the distal end there is a center for each condyle, one for the trochlea and one for the capitulum, the fusion of these various epiphyses with the shaft taking place between the seventeenth and
Fig. 113.  -  The Ossification Centers of the Scapula. a, b, and c, Secondary centers for the angle, vertebral border, and acromion; co, center for the coracoid process.  -  (Testut.)
Fig. 114.  -  Reconstruction of an Embryonic Carpus.
c, Centrale; cu, triquetral; lu, lunate; m, capitate; p, pisiform; sc, navicular; t, greater multangular; tr, lesser multangular; u, hamate.
twentieth years. The radius and ulna each possesses a single epiphysial center for each extremity in addition to the primary center for the shaft, the proximal epiphysial center for the ulna giving rise to the tip of the olecranon process.
The embryological development of the carpus is somewhat complicated. A cartilage is found representing each of the bones normally occurring in the adult (Fig. 114), and these are arranged in two distinct rows: a proximal one consisting of three elements,
named from their relation to the bones of the forearm, radiate, intermedium, and ulnar e; and a distal on^composed of four elements, termed carpalia. In addition, a cartilage, termed the pisiform, is found on the ulnar side of the proximal row ^nd is generally j^g&rded as a sesamoid cartilage developed in the /tendon of the flei ulnaris, and furthermore a number of inconstant carti been observed whose significance in the majority of cast less obscure. These accessory cartilage^either disappc stages of development or fuse with neighboring cartilages^ cases, ossify and form distinct elements of the carpus, however, occurs so frequently as almdK to deserve^ classification as a constant element; it \p known asvthje ceniraie (Fig. 114, c) and occupies a position between the/car\ua!§;es of the proximal and distal rows and apparently correspond ~r&. a cartilage typVally present in lower forms and o^fying*to~f»rai a distinct bone. Iri tha human carpus its fate varies, wfe it may\eitnfer disappear or unitp with other cartilages, that with wpich it most usually fuses b'eing probably the radiale. There is evraence also to sfrftw that another ofJthe accessory cartilages unites/with the ulnar element of the distatsAw, representing the carpale v typically present in lower forms.
Each of the eleinents corresponding to an adu^t) bone ossifies
from a single centerwith the exception of carpale iv-Xwhich has two centers, a furtherindication of its composite character. The relation of the cartrteg&s to the adult bones may be seen from the table given on page loX^J \v_^
With regard toYhe metacarpals and phalanges; it need merely be stated that each develops from a single primary center for the shaft and one secondary epiphysial center. The" primary center appears at about the middle of the shaft excepJ in the terminal phalanges, in which it appears at the distal enfr of the cartilage. The epiphyses for the metacarpals are at the distends of the bones, except in the case of the metacarpal of the ihumb, which resembles the phalanges in having its epiphysis at the proximal end.
Each innominate bone appears as a somewhat oval plate of cartilage whose long axis is directed almost at right angles to the
vertebral column and which is in close relation with the fourth and fifth sacral vertebrae. As development proceeds a rotation of the cartilage, accompanied by a slight shifting of position, occurs, so that eventually the plate has its long axis almost parallel with the vertebral column and is in relation with the first three sacrals. Ossification appears at three points in each cartilage, one in the
upper part to form the ilium (Fig. 115, il) and two in the lower part, the anterior of these giving rise to the pubis (p), while the posterior produces the ischium (is). At birth these three bones are still separated from one another by a Y-shaped piece of cartilage whose three limbs meet at the bottom of the acetabulum, but later a secondary center appears in this cartilage and unites the three bones together. The central part of the lower half of each original cartilage plate does not undergo complete chondrification, but remains membranous, constituting the obturator membrane which closes the obturator foramen. In addition to the Y-shaped secondary center, other epiphysial centers appear in the prominent portions of the cartilage, such as the pubic crest (Fig. 115, c), the ischial tuberosity (d), the anterior inferior spine (b) and the crest of the ilium (a), and unite with the rest of the bone at about the twentieth year.
The femur, tibia, and fibula each develop from a single primary center for the shaft and an upper and a lower epiphysial center, the femur possessing, in addition, epiphysial centers for the greater and lesser trochanters (Fig. 94). The patella does not belong to the same category as the other bones, but resembles the pisiform
Fig. 115.  -  The Ossification Centers of the os innominatum. a, b, c, and d, Secondary centers for the crest, anterior inferior spine, symphysis, and ischial tuberosity; il, ilium; is, ischium; p, pubis.  -  (Testut.)
l8 7
bone of the carpus in being a sesamoid bone, developed in the tendon of the quadriceps extensor cruris. Its cartilage does not appear until the fourth month of intrauterine life, when most of the primary centers for other bones have already appeared, and its ossification does not begin until the third year after birth.
The tarsus, like the carpus, consists of a proximal row of three cartilages, termed the tibiale, the intermedium, and the fibulare, and of a distal row of four tarsalia. Between these two rows a single cartilage, the centrale, is interposed. Each of these cartilages ossifies from a single center, that of the intermedium early fusing with the tibiale, though it occasionally remains distinct as the os trigonum, and from a comparison with lower forms it seems probable that the fibular cartilage of the distal row really represents two separate elements, there being, properly speaking, five tarsalia instead ot four. The fibulare, in addition to its primary center, possesses also an epiphysial center, which develops at the point of insertion of the tendo Achillis.
A comparison of the carpal and tarsal cartilages and their relations to the adult bones may be seen from the following table:
f Tibiale
\ Intermedium
Sesamoid cartilage
-  - 
Fuses with navicular
Carpale I
Gr. multangular
1 st Cuneiform
Tarsale I
Carpale II
Less, multangular
2d Cuneiform
Tarsale II
Carpale III
3d Cuneiform
Tarsale III
Carpale IV 1 Carpale V J
( Tarsale TV I Tarsale V
The development of the metatarsals and phalanges is exactly similar to that of the corresponding bones of the hand (see p. 185).
The Development of the Joints.  -  The mesenchyme which primarily represents each, vertebra, or the skull, or the skeleton of a limb, is at first a continuous mass, and when it becomes converted into cartilage this also may be continuous, as in the skull, or may appear as a number of distinct parts united by unmodified portions of the mesenchyme. In the former case the various ossifications as they extend will come into contact with their neighbors and will either fuse with them or will articulate with them directly, forming a suture.
When, however, a portion of unmodified mesenchyme intervenes between two cartilages, the mode of articulation of the bones formed from these cartilages will vary. The intermediate mesenchyme may in time undergo chondrification and unite the bones in an almost immovable articulation known as a synchondrosis (e. g., the articulation of the first rib with the sternum) ; or a cavity may appear in the center of the intervening cartilage so that a slight amount of movement of the two bones is possible, forming an amphiar thro sis (e. g., the symphysis pubis); or, finally, the intermediate mesenchyme may not chondrify, but its peripheral portions may become converted into a dense sheath of connective tissue (Fig. 116, c) which surrounds the adjacent ends of the two bones like a sleeve, forming the articular capsule, while the central portions degenerate to form a cavity. The bones which enter into such an articulation are more or less freely movable upon one another and the joint is termed a diarthrosis (e. g., the knee- or shoulder-joint).
In a diarthrosis the connective-tissue cells near the inner surface of the capsule arrange themselves in a layer to form a synovial membrane for the joint, and portions of the capsule may thicken to form special bands, the reinforcing ligaments, while other strong fibrous bands, which may pass from one bone to the other, forming accessory ligaments, are shown by comparative studies to be in many cases degenerated portions of what were originally muscles.
In certain diarthroses, such as the temporo-mandibular and
sternoclavicular, the whole of the central portions of the intermediate mesenchyme does not degenerate, but it is converted into a fibro-cartilage, between each surface of which and the adjacent bone there is a cavity. These interarticular cartilages seem, in the sterno-clavicular joints, to represent the sternal ends of a bone existing in lower vertebrates and known as the precoracoid, but it seems doubtful if those of the temporo-mandibular and knee
Fig. 116. -  Longitudinal Section through the Joint oe the Great Toe in an
Embryo of 4.5 cm. c, Articular capsule; i, intermediate mesenchyme which has almost disappeared in the center; p 1 and p 2 , cartilages of the first and second phalanges.  -  (Nicholas.)
joints have a similar significance, the most recent observations on their development tending to derive them from the intermediate mesenchyme.
From their mode of development it is evident that the cavities of diarthrodial joints are completely closed and their walls, except where they are formed by cartilage, are lined by a continuous layer of synovial cells. Ligaments or tendons, which, at first sight, appear to traverse the cavities of certain joints, are in reality excluded from them, being lined by a sheath of synovial cells continuous with the layer fining the general cavity. Thus, the tendon of the long head of the biceps, which seems to traverse the shoulder-joint is, in the fetus, entirely outside the articular capsule, upon which it rests. Later it sinks in toward the joint cavity, pushing the articular capsule before it, so that it lies at first in a groove in the capsule, which later on becomes converted into a canal and, finally, separates from the rest of the capsule except at its two extremities,
forming a cylindrical canal, open at either end, traversing the joint cavity and containing the tendon of the biceps.
The ligamentum teres of the hip-joint is similarly excluded from the joint cavity by a sheath of synovium, which extends outward around it from the bottom of the acetabular fossa to the depression in the head of the femur, and in the knee-joint the crucial ligaments are also excluded from the cavity by a reflection of the synovium. This joint, indeed, is in the fetus incompletely divided into two parts, one corresponding to each femoral condyle, by a partition which extends backward from the patellar ligament to the crucial ligaments, remains of this partition persisting in the adult as the so-called ligamentum mucosum.
C. R. Bardeen: " The Development of the Thoracic Vertebrae in Man," Amer. Journ.
Anat., iv, 1905. C. R. Bardeen: "Studies of the Development of the Human Skeleton," Amer
Journ. Anat. iv, 1905. C. R. Bardeen: "Early Development of the Cervical Vertebra and the Base of the
Occipital Bone in Man," Amer. Journ. Anat., vm, 1908. C. R. Bardeen: "Vertebral Regional Determination in Young Human Embryos,"
Anat. Record, 11, 1908. E. T. Bell: "On the Histogenesis of the Adipose Tissue of the Ox," Amer. Journ.
Anat., ix, 1909. A. Bernays: "Die Entwicklungsgeschichte des Kniegelenks des Menschen mit
Bemerkungen liber die Gelenke im Allgemeinen," Morpholog. Jahrbuch, TV, 1878. E. Dtjrsy: "Zur Entwicklungsgeschichte des Kopfes des Menschen und der hoheren
Wirbelthiere," Tubingen, 1869. E. Fawcett: "On the Development, Ossification and Growth of the Palate Bone,"
Journ. Anat. and Phys., XL, 1906. E. Fawcett: "Notes on the Development of the Human Sphenoid," Journ. Anat.
and Phys., xliv, 1910. E. Fawcett: "The Development of the Human Maxilla, Vomer and Paraseptal Cartilages," Journ. Anat. and Phys., xlv, 1911. A. Froriep: "Zur Entwicklungsgeschichte der Wirbelsaule, insbesondere des Atlas
und Epistropheus und der Occipitalregion," Archiv fur Anat. und Physiol., Anat.
Abth., 1886. E. Gaupp: "Alte Probleme und neuere Arbeiten iiber den Wirbeltierschadel," Ergeb.
der Anat. und Entwicklungsgesch., x, 1901. C. Gegenbaur: "Ein Fall von erblichem Mangel der Pars acromialis Claviculae, mit
Bemerkungen iiber die Entwicklung der Clavicula," Jenaische Zeitschr.filr medic.
Wissensch., I, 1864. J. Golowinski: "Zur Kenntnis der His.togenese der Bindegewebsfibrillen," Anat.
Hefte, xxxiii, 1907.
E. Grafenberg: "Die Entwirklung der Knochen, Muskeln unci Nerven der Hand und
der fur die Bewegungen der Hand bestimmten Muskeln des Unterarms," Anat.
Hefte, xxx, 1906. Henkeand Reyher: "Studien liber die Entwickelung der Extremitaten des Menschen,
insbesondere der Gelenkflachen," Sitzungsberichte der kais. Akad. Wien, LXX, 1875. M. Jakoby: "Beitrag zur Kenntnis des menschlichen Primordialcraniums," Archiv
fiir mikrosk. Anat., xliv, 1894. K. Kjellberg: "Beitrage zur Entwicklungsgeschichte des Kiefergelenks," Morph.
Jahrbuch, xxxii, 1904. H. Leboucq: "Recherches sur la morphologie du carpe chez les mammiferes,"
Archives de Biolog., V, 1884. G. Levi: "Beitrag zum Studium der Entwickelung des knorpeligen Primordialcraniums des Menschen," Archiv fiir mikrosk. Anat., lv, 1900. A. Linck: "Beitrage zur Kennlnis der menschlichen Chorda dorsalis in Hals- und
Kopfskelett, etc.," Anat. Hefte, xlii, 1911. A. Low: "Further Observations on the Ossification of the Human Lower Jaw,"
Journ. Anat. and Phys., xliv, 1910. M. Lucien: " Developpement de l'articulation du genou et formation du ligament
adipeux," Bibliogr. Anat., xiii, 1904.
F. P. Mall: "The Development of the Connective Tissues from the Connective-tissue
Syncytium," Amer. Jour. Anat., 1, 1902. F. P. Mall: "On Ossification Centers in Human Embryos Less Than One Hundred Days Old," Amer. Journ. Anat., V 1906.
F. Merkel: "Betrachtungen fiber die Entwicklung des Bindegewebes," Anat. Hefte,
xxxviii, 1909. W. van Noorden: "Beitrag zur Anatomie der knorpeligen Schadelbasis menschlicher
Embryonen," Archiv fiir Anat. und Physiol., Anat. Abth., 1887. A. M. Paterson: "The Human Sternum," Liverpool, 1904. K. Peter: " Anlage und Homologie der Muscheln des Menschen und der Saugetiere,"
Arch, fur mikrosk. Anat., lx, 1902. J. W. Pryor: "The Chronology and Order of Ossification of the Bones of the Human
Carpus," Bulletin State Univ., Lexington, Ky., 1908. Rambaut et Renault: "Origine et developpement des Os," Paris, 1864. E. Rosenberg: "Ueber die Entwickelung der Wirbelsaule und das Centrale carpi des
Menschen," Morpholog. Jahrbuch, 1, 1876. H. and H. Rouviere: "Sur le developpement de l'antre mastoidien et les cellules
mastoidiennes," Bibliogr. Anat., xx, 1910.
G. Ruge: " Untersuchungen liber die Entwickelungsvorgange am Brustbein des Menschen," Morpholog. Jahrbuch, VI, 1880.
J. P. Schaffer: "The Lateral Wall of the Cavum Nasi in Man, with Especial Reference to the Various Developmental Stages," Journ. Morph., xxi, 1910.
J. P. Schaffer: "The Sinus Maxillaris and its Relations in the Embryo, Child and Adult Man," Amer Journ. Anat., x, 1910.
G. Thilenius: "Untersuchungen iiber die morphologische Bedeutung accessorischer Elemente am menschlichen Carpus (und Tarsus)," Morpholog. Arbeiten, V, 1896.
K. Toldt Jr.: "Entwicklung und Struktur des menschlichen Jochbeines," Sitzungsber.
k. Acad. Wissensch. Wien, M ath.-naturwiss Kl., Cxi, 1902. A. Vinogradoff: "Developpement de l'articulation temporo-maxillaire chez l'homme
dans la periode intrauterine," Internal. Monatsschr. Anat. Phys., xxvil, 1910. R. H. Whitehead and J. A. Waddell: "The Early Development of the Mammalian
Sternum," Amer. Journ. Anat., xii, 191 1. L. W. Williams: "The Later Development of the Notochord," Amer. Journ. Anat.,
vin, 1908. E. Zuckerkandl: "Ueber den Jacobsonschen Knorpel und die Ossifikation des
Pflugscharbeines," Sitzb. Akad. Wiss. Wien., cxvn, 1908.
Two forms of muscular tissue exist in the human body, the striated tissue, which forms the skeletal muscles and is under the control of the central nervous system, and the non-striated, which is controlled by the sympathetic nervous system and is found in the skin, in the walls of the digestive tract, the blood-vessels and lymphatics, and in connection with the genito-urinary apparatus. In the walls of the heart a muscle tissue occurs which is frequently regarded as a third form, characterized by being under control of the sympathetic system and yet being striated; it is, however, in its origin much more nearly allied to the non-striated than to the striated form of tissue, and will be considered a variety of the former.
The Histogenesis of Non-striated Muscular Tissue.  -  With the exception of the sphincter and dilator of the pupil and the muscles of the sudoriparous glands, which are formed from the ectoderm, all the non-striated muscle tissue of the body is formed by the conversion of mesenchyme cells into muscle-fibers. The details of this process have been worked out by McGill for the musculature of the digestive and respiratory tracts of the pig and are as follows: The mesenchyme surrounding the mucosa in these tracts is at first a loose syncytium (Fig. 117, m) and in the regions where the muscle tissue is to form a condensation of the mesenchyme occurs followed by an elongation of the mesenchyme cells and their nuclei, so that the muscle layers become clearly distinguishable from the neighboring undifferentiated tissue (Fig. 117, mm). Fibrils of two kinds then begin to appear in the cytoplasm of the muscle cells. Coarse fibrils (f.c) make their appearance as rows of granules, which enlarge and increase in number until they finally fuse to form homogeneous 13 i93
Fig. 117.  -  Longitudinal Section of the Lower Part of the Oesophagus of a Pig Embryo of 15 mm, Showing the Histogenesis of the Non-striated Musculature.
b, Basement membrane; e, epithelium; /.c, coarse fibril;//., fine fibril; ga, ganglion of Auerbach's plexus; gm, ganglion of Meissner's plexus; m, mesenchyne; mm, muscularis mucosae; pb, protoplasmic bridge; vf, varicose fibril.  -  (McCill.)
J 95
fibrils that are at first varicose, but later become of uniform caliber. Fine fibrils (/./) which are homogeneous from the first, make their appearance after the coarse ones and in some cases seem to be formed by the splitting of the latter. They are scattered uniformly throughout the cytoplasm of the muscle cells and increase in number as development proceeds, while the coarse fibrils diminish and may be entirely wanting in the adult tissue.
Some of the mesenchyme cells in each muscle sheet fail to undergo the differentiation just described and multiply to form the interstitial connective tissue, which usually divides the muscle cells into more or less distinct bundles. Traces of the original syncytial nature of the tissue are to be seen in the intercellular bridges that occur between the non-striated muscle cells of many adult forms.
The cells from which the heart musculature develops are at first of the usual well defined embryonic type, but, as development proceeds, they become irregularly stellate in form, the processes of neighboring cells fuse and, eventually, there is formed a continuous mass of protoplasm or syncytium in which all traces of cell boundaries are lacking (Fig. 118). While the individual cells, or myoblasts as they are termed, are still recognizable, granules appear in their cytoplasm, and these arrange themselves in rows and unite to form slender fibrils, which at first do not extend beyond the limits of the myoblasts in which they have appeared, but later, as the fusion of the cells proceeds, are continued from one cell territory into the other
Fig. 118.  -  Section through the Heartwall of a Duck Embryo of Three Days.  -  (M. Heidenhain.)
through considerable stretches of the syncytium, without regard to the original cell areas.
The fibrils multiply, apparently by longitudinal division, and arrange themselves in circles around areas of the syncytium (compare Fig. 119). As the multiplication of the fibrils continues those newly formed arrange themselves around the interior of each of the original circles and gradually occupy the entire cytoplasm, or sarcoplasm as it may now be termed, except immediately around the nuclei where, even in the adult, a certain amount of undifferentiated sarcoplasm persists. The fibrils when first formed are apparently homo
Fig. 119.  -  Cross-section of a Muscle prom the Thigh of a Pig Embryo 75 mm.
Long. A, Central nucleus; B, new peripheral nucleus.  -  (Macallum.)
geneous, but later they become differentiated into two distinct substances which alternate with one another throughout the length of the fibril and produce the characteristic transverse striation of the tissue. Finally stronger interrupted transverse bands of so-called cement substance appear, dividing the tissue into areas which have usually been regarded as representing the original myoblasts, but are really devoid of significance as cells, the tissue remaining, strictly speaking, a syncytium.
The Histogenesis of Striated Muscle Tissue. -  The histogenesis of striated or voluntary muscle tissue resembles very closely that which has just been described for the heart muscle. There is a similar formation of a syncytium by the fusion of the cells of the myotomes, an appearance of granules which unite to form fibrils, an increase of the fibrils by longitudinal division and a primary arrangement of the fibrils around the periphery of areas of sarcoplasm (Fig. 119), each of which represents a muscle fiber. In addition there is an active proliferation of the nuclei of the original myoblasts, the new nuclei arranging themselves more or less regularly in rows and later migrating from their original central position to the periphery of the fibers, and, in the limb muscles, the development is further complicated by a process of degeneration which affects groups of muscle fibers, so that bundles of normal fibers are separated by strands of degenerated tissue in which the fibrils have disappeared, the nuclei have become pale and the sarcoplasm vacuolated and homogeneous. Later the degenerated tissue seems to disappear entirely and mesenchymatous connective tissue grows in between the persisting fibers, grouping them into bundles and the bundles into the individual muscles.
So long as the formation of new fibrils continues, the increase in the thickness of a muscle is probably due to a certain extent to an increase in the actual number of fibers, which results from the division of those already existing. Subsequently, however, this mode of growth ceases, the further increase of the muscle depending upon an increase in size of its constituent elements (Macallum).
The Development of the Skeletal Muscles.  -  It has already been pointed out that all the skeletal muscles of the body, with the exception of those connected with the branchial arches, are derived from the myotomes of the mesodermic somites, even the limb muscles possibly having such an origin, although the cells of the tissue from which the muscles of the limb buds form lack an epithelial arrangement and are indistinguishable from the somatic mesenchyme which forms the axial cores of the limbs.
The various fibers of each myotome are at first loosely arranged,
but later they become more compact and are arranged parallel with one another, their long axes being directed antero-posteriorly. This stage is also transitory, however, the fibers of each myotome undergoing various modifications to produce the conditions existing in the adult, in which the original segmental arrangement of the fibers can be perceived in comparatively few muscles. The exact nature of these modifications is almost unknown from direct observation, but since the relation between a nerve and the myotome belonging to the same segment is established at a very early period of development and persists throughout life, no matter what changes of fusion, splitting, or migration the myotome may undergo, it is possible to trace out more or less completely the history of the various myotomes by determining their segmental innervation. It is known, for example, that the latissimus dorsi arises from the seventh and eighth* cervical myotomes, but later undergoes a migration, becoming attached to the lower thoracic and lumbar vertebrae and to the crest of the ilium, far away from its place of origin (Mall), and yet it retains its nerve-supply from the seventh and eighth cervical nerves with which it was originally associated, its nerve-supply consequently indicating the extent of its migration.
By following the indications thus afforded, it may be seen that the changes which occur in the myotomes may be referred to one or more of the following processes:
1. A longitudinal splitting into two or more portions, a process well illustrated by the trapezius and sternomastoid, which have differentiated by the longitudinal splitting of a single sheet and contain therefore portions of the same myotomes. The sternohyoid and omohyoid have also differentiated by the same process, and, indeed, it is of frequent occurrence.
2. A tangential splitting into two or more layers. Examples of this are also abundant and are afforded by the muscles of the fourth, fifth, and sixth layers of the back, as recognized in English text-books
* This enumeration is based on convenience in associating the myotomes with the nerves which supply them. The myotomes mentioned are those which correspond to the sixth and seventh cervical vertebrae.
of anatomy, by the two oblique and the transverse layers of the abdominal walls, and by the intercostal muscles and the transversus of the thorax.
3. A fusion of portions of successive myotomes to form a single muscle, again a process of frequent occurrence, and well illustrated by the rectus abdominis (which is formed by the fusion of the ventral portions of the last six or seven thoracic myotomes) or by the superficial portions of the sacro-spinalis.
4. A migration of parts of one or more myotomes over others. An example of this process is to be found in the latissimus dorsi, whose history has already been referred to, and it is also beautifully shown by the serratus anterior and the trapezius, both of which have extended far beyond the limits of the segments from which they are derived.
5. A degeneration of portions or the whole of a myotome. This process has played a very considerable part in the evolution of the muscular system in the vertebrates. When a muscle normally degenerates, it becomes converted into connective tissue, and many of the strong aponeurotic sheets which occur in the body owe their origin to this process. Thus, for example, the aponeurosis connecting the occipital and frontal portions of the occipito-frontalis is formed in this process and is muscular in such forms as the lower monkeys, and a good example is also to be found in the aponeurosis which occupies the interval between the superior and inferior serrati postici, these two muscles being continuous in lower forms. The strong lumbar aponeurosis and the aponeuroses of the oblique and transverse muscles of the abdomen are also good examples.
Indeed, in comparing one of the mammals with a member of one of the lower classes of vertebrates, the greater amount of connective tissue compared with the amount of muscular tissue in the former is very striking, the inference being that these connectivetissue structures (fasciae, aponeuroses, ligaments) represent portions of the muscular tissue of the lower form (Bardeleben). Many of the accessory ligaments occurring in connection with diarthrodial joints apparently owe their origin to a degeneration of muscle tissue, the
fibular lateral ligament of the knee-joint, for instance, being probably a degenerated portion of the peroneus longus, while the sacrotuberous ligament appears to stand in a similar relation to the long head of the biceps femoris (Sutton).
6. Finally, there may be associated with any of the first four processes a change in the direction of the muscle-fibers. The original antero-posterior direction of the fibers is retained in comparatively few of the adult muscles and excellent examples of the process here referred to are to be found in the intercostal muscles and the muscles of the abdominal walls. In the musculature associated with the branchial arches the alteration in the direction of the fibers occurs even in the fishes, in which the original direction of the muscle-fibers is very perfectly retained in other myotomes, the branchial muscles, however, being arranged parallel with the branchial cartilages or even passing dorso-ventrally between the upper and lower portions of an arch, and so forming what may be regarded as a constrictor of the arch. This alteration of direction dates back so far that the constrictor arrangement may well be taken as the primary condition in studying the changes which the branchial musculature has undergone in the mammalia.
It would occupy too much space 'in a work of this kind to consider in detail the history of each one of the skeletal muscles of the human body, but a statement of the general plan of their development will not be out of place. For convenience the entire system may be divided into three portions  -  the cranial, trunk and limb musculature; and of these, the trunk musculature may first be considered.
The Trunk Musculature.  -  It has already been seen (p. 82) that the myotomes at first occupy a dorsal position, becoming prolonged ventrally as development proceeds so as to overlap the somatic mesoderm, until those of opposite sides come into contact in the mid-ventral line. Before this is accomplished, however, a longitudinal splitting of each myotome occurs, whereby there is separated off a dorsal portion which gives rise to a segment of the dorsal musculature of the trunk and is supplied by the ramus dorsalis
of its corresponding spinal nerve. In the lower vertebrates this separation of each of the trunk myotomes into a dorsal and ventral portion is much more distinct in the adult than it is in man, the two portions being separated by a horizontal plate of connective tissue extending the entire length of the trunk and being attached by its inner edge to the transverse processes of the vertebrae, while peripherally it becomes continuous with the connective tissue of the
Fig. 120.  -  Embryo of 13 mm. showing the Formation of the Rectus Muscle. - 
dermis along a line known as the lateral line. In man the dorsal portion is also much smaller in proportion to the ventral portion than in the lower vertebrates. From this dorsal portion of the myotomes are derived the muscles belonging to the three deepest layers of the dorsal musculature, the more superficial layers being
composed of muscles belonging to the limb system. Further longitudinal and tangential divisions and a fusion of successive myotomes bring about the conditions which obtain in the adult dorsal musculature.
While the myotomes are still some distance from the mid-ventral line another longitudinal division affects their ventral edges (Fig. 120), portions being thus separated which later fuse more or less perfectly to form longitudinal bands of muscle, those of opposite sides being brought into apposition along the mid-ventral line by the continued growth ventrally of the myotomes. In this way are formed the rectus and pyramidalis muscles of the abdomen and the depressors of the hyoid bone, the genio-hyoid and genio-glossus* in the neck region. In the thoracic region this rectus set of muscles, as it may be termed, is not represented except as an anomaly, its absence being probably correlated with the development of the sternum in this region.
The lateral portions of the myotomes which intervene between the dorsal and rectus muscles divide tangentially, producing from their dorsal portions in the cervical and lumbar regions muscles, such as the longus capitis and colli and the psoas, which lie beneath the vertebral column and hence have been termed hyposkeletal muscles (Huxley). More ventrally three sheets of muscles, lying one above the other, are formed, the fibers of each sheet being arranged in a definite direction differing from that found in the other sheets. In the abdomen there are thus formed the two oblique and the transverse muscles, in the thorax the intercostals and the transversa thoracis, while in the neck these portions of some of the myotomes disappear, those of the remainder giving rise to the scaleni muscles, portions of the trapezius and sternomastoid (Bolk), and possibly the hyoglossus and styloglossus. In the abdominal region, and to a considerable extent in the neck also, the various portions of myotomes fuse together, but in the thorax they retain in the intercostals their original distinctness, being separated by the ribs.
* This muscle is supplied by the hypoglossal nerve, but for the present purpose it is convenient to regard this as a spinal nerve, as indeed it primarily is.
to • «
cd u
m p
L u
cd ft
ohyoid nothyr reohyc
c c
O 00 h
.. . ,
3 Ul
"3 d
> en
- - .
â– 3
_2 .2
<d >^
in ed
"2 c H
In 41 >
d cd
u u
The table on page 203 will show the relation of the various trunk muscles to the portions of the myotomes.
The intimate association between the pelvic girdle and the axial skeleton brings about extensive modifications of the posterior trunk myotomes. So far as their dorsal portions are concerned probably all these myotomes as far back as the fifth sacral are represented in the sacro-spinalis, but the ventral portions from the first lumbar myotome onward are greatly modified. The last myotome taking part in the formation of the rectus abdominis is the twelfth thoracic and the last to be represented in the lateral musculature of the
Fig. 121.  -  Perineal Region of Embryos of (A) Two Months and (25) Four to
Five Months, showing the Development of the Perineal Muscles.
dc, Nervus dorsalis clitoridis; p, pudendal nerve; sa, sphincter ani; sc sphincter cloacae;
sv, sphincter vaginse.  -  (Popowsky.)
abdomen is the first lumbar, the ventral portions of the remaining lumbar and of the first and second sacral myotomes either having disappeared or being devoted to the formation of the musculature of the lower limb.
The ventral portions of the third and fourth sacral myotomes are represented, however, by the levator ani and coccygeus, and are the last myotomes which persist as muscles in the human body, although traces of still more posterior myotomes are to be found in muscles such as the curvator coccygis sometimes developed in connection with the coccygeal vertebrae.
The perineal muscles and the external sphincter ani are also
developments of the third and fourth (and second) sacral myotomes. At a time when the cloaca (see p. 280) is still present, a sheet of muscles lying close beneath the integument forms a sphincter around its opening (Fig. 121). On the development of the partition which divides the cloaca into rectal and urinogenital portions, the sphincter is also diyided, its more posterior portion persisting as the external sphincter ani, while the anterior part gradually differentiates into the various perineal muscles (Popowsky).
The Cranial Musculature.  -  As was pointed out in an earlier chapter, the existence of distinct mesodermic somites has not yet been completely demonstrated in the head of the human embryo, but in lower forms, such as the elasmobranch fishes, they are clearly distinguishable, and it may be supposed that their indistinctness in man is a secondary condition. Exactly how many of these somites are represented in the mammalian head it is impossible to say, but it seems probable, from comparison with lower forms, that there is a considerable number. The majority of them, however, early undergo degeneration, and in the adult condition only three are recognizable, two of which are prseoral in position and one postoral. The myotomes of the anterior praeoral segment give rise to the muscles of the eye supplied by the third cranial nerve, those of the posterior one furnish the superior oblique muscles innervated by the fourth nerve, while from the postoral myotomes the lateral recti, supplied by the sixth nerve, are developed. The muscles supplied by the hypoglossal nerve are also derived from myotomes, but they have already been considered in connection with the trunk musculature.
The remaining muscles of the head differ from all other voluntary muscles of the body in the fact that they are derived from the branchiomeres formed by the segmentation of the cephalic ventral mesoderm. These muscles, therefore, are not to be regarded as equivalent to the myotomic muscles if their embryological origin is to be taken as a criterion of equivalency, and in their case it would seem, from the fact that they are innervated by nerves fundamentally distinct from those which supply the myotomic muscles, that this
criterion is a good one. They must be regarded, therefore, as belonging to a special category, and may be termed branchiomeric muscles to distinguish them from the myotomic set.
If their embryological origin be taken as a basis for homology, it is clear that they should be regarded as equivalent to the muscles derived from the ventral mesoderm of the trunk, and these, as has been seen, are the non-striated muscles associated with the viscera, among which may be included the striated heart muscle. At first sight this homology seems decidedly strained, chiefly because long-continued custom has regarded the histological and physiological peculiarities of striated and non-striated muscle tissue as fundamental. It may be pointed out, however, that the branchiomeric muscles are, strictly speaking, visceral muscles, and indeed give rise to muscle sheets (the constrictors of the pharynx) which surround the upper or pharyngeal portion of the digestive tract. It is possible, then, that the homology is not so strained as might appear, but further discussion of it may profitably be deferred until the cranial nerves are under consideration.
The skeleton of the first branchial arch becomes converted partly into the jaw apparatus and partly into auditory ossicles, and the muscles derived from the corresponding branchiomere become the muscles of mastication (the temporal, masseter, and pterygoids), the mylohyoid, anterior belly of the digastric, the tensor veli palatini and the tensor tympani. The nerve which corresponds to the first branchial arch is the trigeminus or fifth, and consequently these various muscles are supplied by it.
The second arch has corresponding to it the seventh nerve, and its musculature is partly represented by the stylohyoid and posterior belly of the digastric and by the stapedius muscle of the middle ear. From the more superficial portions of the branchiomere, however, a sheet of tissue arises which gradually extends upward and downward to form a thin covering for the entire head and neck, its lower portion giving rise to the platysma and the nuchal fascia which extends backward from the dorsal border of this muscle, while its upper parts become the occipito-frontalis and the superficial muscles of the face (the muscles of expression), together with the fascia? which unite the various muscles of this group. The extension of the platysma sheet of muscles over the face is well shown by the
Fig. 122.  -  Head of Embryos (.4) of Two Months and (B) of Three Months showing the Extension of the Seventh Nerve upon the Face.  -  (Popowsky.)
development of the branches of the facial nerve which supply it (Fig. 122).
The degeneration of the upper part of the third arch produces a shifting forward of one of the muscles derived from its branchiomere, the stylopharyngeus arising from the base of the styloid process. The innervation of this muscle by the ninth nerve indicates, however, its true significance, and since fibers of this nerve of the third arch also pass to the constrictor muscles of the pharynx, a portion of these must also be regarded as having arisen from the third branchiomere.
The cartilages of the fourth and fifth arches enter into the formation of the larynx and the muscles of the corresponding branchiomeres constitute the muscles of the larynx, together with the remaining portions of the constrictors of the pharynx and the muscles of the soft palate, with the exception of the tensor. Both these arches have branches of the tenth nerve associated with them and hence this nerve supplies the muscles named. In addition, two of the extrinsic muscles of the tongue, the glosso-palatinus and chondroglossus, belong to the fourth or fifth branchiomere, although the remaining muscles of this physiological set are myotomic in origin.
Finally, portions of two other muscles should probably be included in the list of branchiomeric muscles, these muscles being the trapezius and sternomastoid. It has already been seen that they are partly derived from the cervical myotomes, but they are also innervated in part by the spinal accessory, and since the motor fibers of this nerve are serially homologous with those of the vagus it would seem that the muscles which they supply are probably branchiomeric in origin. Observations on the development of these muscles, determining their relations to the branchiomeres, are necessary, however, before their morphological significance can be regarded as definitely settled.
The table on page 209 shows the relations of the various cranial muscles to the myotomes and branchiomeres, as well as to the motor cranial nerves.
Trapezius. Sternomastoid.
Constrictors of pharynx (in part). Pharyngopalatinus. Levator veli palatini. Musculus
uvulae. Muscles of the larynx. Glosso-pal
â– 5 .S
of pharynx
(in part).
> <U CO
Stapedius. Platysma. Occipitofrontalis.
Muscles of
a) 3
h-1 M
Temporal. . Masseter.
Tensor veli
O u CO O
•A <u 3
Superior Inferior Medial _ Inferior
«5 <u "0
'in U
% I
The Limb Muscles.  -  It has been customary to regard the limb muscles as derivatives of certain of the myotomes, these structures in their growth vent rally in the trunk walls being supposed to pass out upon the postaxial surface of the limb buds and loop back again to the trunk along the praeaxial surface, each myotome thus giving rise to a portion of both the dorsal and the ventral musculature of the limb. This view has not, however, been verified by direct observation of an actual looping of the myotomes over the axis of the limb buds; indeed, on the contrary, the limb muscles have been found to develop from the cores of mesenchyme which form the axes of the limb buds and from which the limb skeleton is also developed. This may be explained by supposing that the limb muscles are primarily derivatives of the myotomes and that an extensive concentration of their developmental history has taken place, so that the axial mesenchyme actually represents myotomic material even though no direct connection between it and the myotomes can be discovered. Condensations of the developmental history certainly occur and the fact that the muscles of the human limbs, as they differentiate from the axial cores, present essentially the same arrangement as in the adult seems to indicate that there is actually an extensive condensation of the phylogenetic history of the individual muscles, since comparative anatomy shows the arrangement of the muscles of the higher mammalian limbs to be the result of a long series of progressive modifications from a primitive condition. However, even though this be the case, there is yet the possibility that the limb musculature, like the limb skeleton, may take its origin from the ventral mesoderm and consequently belong to a different embryological category from the axial myotomic muscles.
The strongest evidence in favor of the myotomic origin of the limb muscles is that furnished by their nerve supply, this presenting a distinctly segmental arrangement. This does not necessarily imply, however, a corresponding primarily metameric arrangement of the muscles, any more than the pronouncedly segmental arrangement of the cutaneous nerves implies a primary metamerism of the
dermis (see p. 143). It may mean only that the nerves, being segmental, retain their segmental relations to one another even in their distribution to non-metameric structures, and that, consequently, the limb musculature is supplied in succession from one border of the limb bud to the other from succeeding nerve roots.
But whether further observation may prove or disprove the myotomic origin of the limb musculature, the fact remains that it possesses a segmentally arranged innervation, and it is possible,
Fig. 123.  -  Diagram of a Segment of the Body and Limb. bl, Axial blastema; dm, dorsal musculature of trunk; rl, nerve to limb; s, septum between dorsal and ventral trunk musculature; str.d, dorsal layer of limb musculature; tr.d and tr.v, dorsal and ventral divisions of a spinal nerve; vm, ventral musculature of the trunk.  -  (Kollmann.)
therefore, to recognize in the limb buds a series of parallel bands of muscle tissue, extending longitudinally along the bud and each supplied by a definite segmental nerve. And furthermore, corresponding to each band upon the ventral (praeaxial) surface of the limb bud, there is a band similarly innervated upon the dorsal (postaxial) surface, since the fibers which pass to the limb from each nerve root sooner or later arrange themselves in praeaxial and postaxial
groups as is shown in the diagram Fig. 123. The first nerve which enters the limb bud lies along its anterior border, and consequently the muscle bands which are supplied by it will, in the adult, lie along
Fig. 124.  -  External Surface of the Os Innominatum showing the Attachment
of Muscles and the Zones Supplied by the Various Nerves.
12, Twelfth thoracic nerve; I to V, lumbar nerves; 1 and 2, sacral nerves.  -  (Bolk.)
the outer side of the arm and along the inner side of the leg, in consequence of the rotation in opposite directions which the limbs undergo during development (see p. 101).
The first nerve which supplies the muscles attached to the dorsum of the ilium is the second lumbar, and following that there come successively from before backward the remaining lumbar and the
Fig. 125.  -  Sections through (A) the Thigh and (B) the Calf showing the Zones Supplied by the Nerves. The Nerves are Numbered in Continuation with the Thoracic Series.  -  (A, after Bolk.)
first and second sacral nerves. The arrangement of the muscle bands supplied by these nerves and the muscles of the adult to which they contribute may be seen from Fig. 124. What is shown there is only the upper portions of the postaxial bands, their lower portions
extending downward on the anterior surface of the leg. Only the sacral bands, however, extend throughout the entire length of the limb into the foot, the second lumbar band passing down only to about the middle of the thigh, the third to about the knee, the fourth to about the middle of the crus and the fifth as far as the base of the fifth metatarsal bone, and the same is true of the corresponding praeaxial bands, which descend from the ventral surface of the os coxae (innominatum) along the inner and posterior surfaces of the leg to the same points. The first and second sacral bands can be traced into the foot, the first giving rise to the musculature of its
Fig. 126.  -  Section through the Upper Part of the Arm showing the Zones Supplied by the Nerves.
$v to jv, Ventral branches; 5J to Sd, dorsal branches of the cervical nerves. -  (Bolk.)
inner side and the second to that of its outer side, the praeaxial bands forming the plantar musculature, while the postaxial ones are upon the dorsum of the foot as a result of the rotation which the limb has undergone.
In a transverse section through a limb at any level all the muscle bands, both praeaxial and postaxial, which descend to that level will be cut and will lie in a definite succession from one border of the limb to the other, as is seen in Fig. 125. In the differentiation of the individual muscles which proceeds as the nerves extend from the trunk into the axial mesenchyme of the limb, the muscle bands
undergo modifications similar to those already described as occurring in the trunk myotomes. Thus, each of the muscles represented in Fig. 125, B, is formed by the fusion of elements derived from two or more bands; the soleus and gastrocnemius represent deep and superficial layers formed from the same bands by a horizontal (tangential) splitting, these same muscles contain a portion of the second sacral band which overlaps muscles composed only of higher myotomes, and the intermuscular septum between the peroneus brevis and the flexor hallucis longus represents a portion of the third sacral band which has degenerated into connective tissue.
A similar arrangement occurs in the bands which are to be recognized in the musculature of the upper limb. These are supplied by the fourth, fifth, sixth, seventh and eighth cervical and the first thoracic nerves, and only those supplied by the eighth cervical and the first thoracic nerves extend as far as the tips of the fingers. The arrangement of the bands in the upper part of the brachium may be seen from Fig. 126, in connection with which it must be noted that the fourth cervical band does not extend down to the level at which the section is taken and that the praeaxial band of the eighth cervical nerve and both the praeaxial and postaxial bands of the first thoracic are represented only by connective tissue in this region.
In another sense than the longitudinal one there is a division of the limb musculature into more or less definite areas, namely, in a transverse direction in accordance with the jointing of the skeleton. Thus, there may be recognized a group of muscles which pass from the axial skeleton to the pectoral girdle, another from the limb girdle to the brachium or thigh, another from the brachium or thigh to the antibrachium or crus, another from the antibrachium or crus to the carpus or tarsus, and another from the carpus or tarsus to the digits. This transverse segmentation, if it may be so termed, is not, however, perfectly definite, many muscles, even in the lower vertebrates, passing over more than one joint, and in the mammalia, especially, it is further obscured by secondary migrations, by the partial degeneration of muscles and by an end to end union of primarily distinct muscles.
The latissimus dorsi, serratus anterior and pectoral muscles are all examples of a process of migration as is shown by their innervation from cervical nerves, as well as by the actual migration which has been traced in the developing embryo (Mall, Lewis). In the lower limb evidences of migration may be seen in the femoral head of the biceps, comparative anatomy showing this to be a derivative of the gluteal set of muscles which has secondarily become attached to the femur and has associated itself with a praeaxial muscle to form a compound structure. An appearance of migration may also be produced by a muscle making a secondary attachment below its original origin or above the insertion and the upper or lower part, as the case may be, then degenerating into connective tissue. This has been the case with the peroneus longus, which, in the lower mammals, has a femoral origin, but has in man a new origin from the fibula, its upper portion being represented by the fibular lateral ligament of the knee-joint. So too the pectoralis minor is primarily inserted into the humerus, but it has made a secondary attachment to the coracoid process, its distal portion forming a coraco-humeral ligament.
The comparative study of the flexor muscles of the antibrachial and crural regions has yielded abundant evidence of extensive modifications in the differentiation of the limb muscles. In the tailed amphibia these muscles are represented by a series of superposed layers, the most superficial of which arises from the humerus or femur, while the remaining ones take their origin from the ulna or fibula and are directed distally and laterally to be inserted either into the palmar or plantar aponeurosis, or, in the case of the deeper layers, into the radius (tibia) or carpus (tarsus). In the arm of the lower mammalia the deepest layer becomes the pronator quadratus, the lateral portions of the superficial layer are the flexor carpi ulnaris and the flexor carpi radialis, while the intervening layers, together with the median portion of the superficial one, assuming a more directly longitudinal direction, fuse to form a common flexor mass which acts on the digits through the palmar aponeurosis. From this latter structure and from the carpal and metacarpal bones five
layers of palmar muscles take origin. The radial and ulnar portions of the most superficial of these become the flexor pollicis brevis and abductor pollicis brevis and the abductor quinti digiti, while the rest of the layer degenerates into connective tissue, forming tendons
Fig. 127.  -  Transverse sections through (A) the forearm and (B) the hand showing the arrangement of the layers of the flexor muscles. The superficial layer is shaded horizontally, the second layer vertically, the third obliquely to the left, the fourth vertically, and the fifth obliquely to the right. AbM, abductor digiti quinti; AdP, adductor pollicis; BR, brachio-radialis; ECD, extensor digitorum communis; ECU, extensor carpi ulnaris;£Z, extensor indicis; EMD, extensor digiti quinti; EMP, abductor pollicis longus; ERB, extensor carpi radialis brevis; FCR, flexor carpi radialis; FCU, flexor carpi ulnaris; FLP, flexor pollicis longus; FM, flexor digiti quinti brevis; FP, flexor digitorum profundus; FS, flexor digitorum sublimis; ID, interossei dorsales; IV, interossei volares; L, lumbricales; OM, opponens digiti quinti; PL, palmaris longus; PT, pronator teres; R, radius; U, ulna; II-V, second to fifth metacarpal.
which pass to the four ulnar digits. Gradually superficial portions of the antibrachial flexor mass separate off, carrying with them the layers of the palmar aponeurosis from which the tendons representing
the superficial layer of the palmar muscles arise, and they form with these the flexor digitorum sublimis. The deeper layers of the antibrachial flexor mass become the flexor digitorum profundus and the flexor pollicis longus (Fig. 127, A), and retain their connection with the deeper layers of the palmar aponeurosis which form their tendons; and since the second layer of the palmar muscles takes origin from this portion of the aponeurosis it becomes the lumbrical muscles, arising from the profundus tendons (Fig. 127,
Fig. 128.  -  Transverse sections through (A) the crus and (B) the foot, showing the arrangement of the layers of the flexor muscles. The shading has the same significance as in the preceding figure. AbH, abductor hallucis; AbM, abductor minimi digiti; AdH, adductor hallucis; ELD, extensor longus digitorum; F, fibula; FBD, flexor brevis digitorium; FBH, flexor brevis hallucis; FBM, flexor brevis minimi digiti; FLD, flexor longus digitorum; G, gastrocnemius; ID, interossei dorsalis; IV, interossei ventrales; L, lumbricales; P, plantaris; Pe, peroneus longus; Po, popliteus; S, soleus; T, tibia; TA, tibialis anticus; TP, tibialis posticus; I-V, first to fifth metatarsal.
B). The third layer of palmar muscles becomes the adductors of the digits, reduced in man to the adductor pollicis, while from the two deepest layers the interossei are developed. Of these the fourth layer consists primarily of a pair of slips corresponding to each digit, while the fifth is represented by a series of muscles which extend obliquely across between adjacent metacarpals. With these last muscles certain of the fourth layer slips unite to form the dorsal interossei, while the rest become the volar interossei. j The modifications of the almost identical primary arrangement in the crus and foot are somewhat different. The superficial layer
of the crural flexors becomes the gastrocnemius and plantaris (Fig. 128, A) and the deepest layer becomes the popliteus and the interosseous membrane. The second and third layers unite to form a common mass which is inserted into the deeper layers of the plantar aponeurosis and later differentiates into the soleus and the long digital flexor, the former shifting its insertion from the plantar aponeurosis to the os calcis, while the flexor retains its connection with the deeper layers of the aponeurosis, these separating from the superficial layer to form the long flexor tendons. The fourth layer partly assumes a longitudinal direction and becomes the tibialis posterior and the flexor hallucis longus and partly retains its original cblique direction and its connection with the deep layers of the plantar aponeurosis, becoming the quadratus plantse. In the foot (Fig. 128, B) the superficial layer persists as muscular tissue, forming the abductors, the flexor digitorum brevis and the medial head of the flexor hallucis brevis, the second layer becomes the lumbricales, and the third the lateral head of the flexor hallucis brevis and the adductor hallucis, while the fourth and fifth layers together form the ioterossei, as in the hand, the flexor quinti digiti brevis really belonging to that group of muscles.
C. R. Bardeen and W. H. Lewis: "Development of the Limbs, Body-wall, and
Back in Man," The American Journal of Anat., 1, 1901. K. Bardeleben: "Musk el und Fascia," Jenaische Zeitschr. fiir Naturwissensch.,
xv, 1882. L. Bolk: "Beziehungen zwischen Skelett, Muskulatur und Nerven der Extremitaten,
dargelegt am Beckengurtel, an dessen Muskulatur sowie am Plexus lumbo
sacralis," Morphol. Jahrbuch, xxi, 1894. L. Bolk: " Rekonstruktion der Segmentirung der Gliedmassenmuskulatur dargelegt
an den Muskeln des Oberschenkels und des Schultergurtels," Morphol. Jahrbuch,
xxii, 1895. L. Bolk: "Die Sklerozonie des Humerus," Morphol. Jahrbuch, xxill, 1S96. L. Bolk: "Die Segmentaldifferenzierung des menschlichen Rumpfes und seiner
Extremitaten," 1, Morphol. Jahrbuch, xxv, 1898. R. Futamtjra: "Ueber die Entwickelung der Facialismuskulatur des Menschen,"
Anat. Hefte, xxx, 1906. E. Godlewski: "Die Entwicklung des Skelet- und Herzmuskelgewebes der Sauge
thiere," Archiv fur mikr. Anat., lx, 1902.
E. Grafenberg: "Die Entwicklung der menschlichen Beckenmuskulatur," Anal.
Hefte, xxiii, 1904. W. P. Herringham: "The Minute Anatomy of the Brachial Plexus," Proceedings
of the Royal Soc. London, xli, 1886. W. H. Lewis: " The Development of the Arm in Man," Amer. Jour, of Anat., 1, 1902 J. B. MacCallum: "On the Histology and Histogenesis of the Heart Muscle-cell,"
Anat. Anzeiger, xiil, 1897. J. B. MacCallum: "On the Histogenesis of the Striated Muscle-fiber and the
Growth of the Human Sartorius Muscle," Johns Hopkins Hospital Bulletin, 1898
F. P. Mall: "Development of the Ventral Abdominal Walls in Man," Journ. of
Morphol., xiv, 1898. Caroline McGill: "The Histogenesis of Smooth Muscle in the Alimentary Canal
and Respiratory Tract of the Pig," Internat. Monatschr. Anat. und Phys., xxiv,
1907. J. P. McMurrich: "The Phylogeny of the Forearm Flexors," Amer. Journ, of Anat.,
11, 1903. J. P. McMurrich: "The Phylogeny of the Palmar Musculature," Amer. Journ. of
Anat., 11, 1903. J. P. McMurrich: "The Phylogeny of the Crural Flexors," Amer. Journ. of Anat.,
iv, 1904. J. P. McMurrich: "The Phylogeny of the Plantar Musculature," Amer. Journ. of
Anat., vi, 1907.
A. Meek: "Preliminary Note on the Post-embryonal History of Striped Muscle-fibers
in Mammalia," Anat. Anzeiger, xiv, 1898. (See also Anat. Anzeiger, xv, 1899.)
B. Morpurgo: "Ueber die post-embryonale Entwickelung der quergestreiften Muskel
von weissen Ratten," Anat. Anzeiger, xv, 1899. I. Popowsky: " Zur Entwicklungsgeschichte des N. facialis beim Menschen," Morphol.
Jahrbuch, xxiii, 1896. I. Popowsky: " Zur Entwickelungsgeschichte der Dammmuskulatur beim Menschen,"
Anat. Hefte, xi, 1899. L. Rethi: "Der peripheren Verlauf der motorischen Rachen- und Gaumennerven,"
Sitzungsber. der kais. Akad. Wissensch. Wien. Math.-Naturwiss. Classe, Cii, 1893.
C. S. Sherrington: " Notes on the Arrangement of Some Motor Fibers in the Lumbo
sacral Plexus," Journal of Physiol., xin, 1892. J. B. Sutton: "Ligaments, their Nature and Morphology," London, 1897.
At present nothing is known as to the earliest stages of development of the circulatory system in the human embryo, but it may be supposed that they resemble in their fundamental features what has been observed in such forms as the rabbit and the chick. In both these the system originates in two separate parts, one of which, located in the embryonic mesoderm, gives rise to the heart, while the other, arising in the extra-embryonic mesoderm, forms the first blood-vessels. It will be convenient to consider these two parts separately, and the formation of the blood-vessels may be first described.
In the rabbit the extension of the mesoderm from the embryonic region, where it first appears, over the yolk-sac is a gradual process, and it is in the more peripheral portions of the layer that the bloodvessels first make their appearance. They can be distinguished before the splitting of the mesoderm has been completed, but are always developed in that portion of the layer which is most intimately associated with the yolk-sac, and consequently becomes the splanchnic layer. They belong, indeed, to the deeper portion of that layer, that nearest the endoderm of the yolk-sac, and so characteristic is their origin from this portion of the layer that it has been termed the angioblast and has been held to be derived from the endoderm independently of the mesoderm proper. The first indication of blood-vessels is the appearance in the peripheral portion of the mesoderm of cords or minute patches of spherical cells (Fig. 129, .4). These increase in size by the division and separation of the cells from one another (Fig. 129, B), a clear fluid appearing in the intervals which separate them. Soon the cells surrounding each cord arrange
themselves to form an enclosing wall, and the cords, increasing in size, unite together to form a network of vessels in which float the spherical cells which may be known as mesamceboids (Minot). Viewed from the surface at this stage a portion of the vascular area of the mesoderm would have the appearance shown in Fig. 130, revealing a dense network of canals in which, at intervals, are groups of mesamaeboids adherent to the walls, constituting what have been termed the blood-islands, while in the meshes of the network unaltered mesoderm cells can be seen, forming the so-called substance-islands.
Fig. 129.  -  Transverse Section through the Area Vasculosa of Rabbit Embryos showing the Transformation of Mesoderm cells into the Vascular Cords.
Ec, Ectoderm; En, endoderm; Me, mesoderm.  -  (van der Stricht.)
At the periphery of the vascular area the vessels arrange themselves to form a sinus terminalis enclosing the entire area, and the vascularization of the splanchnic mesoderm gradually extends toward the embryo. Reaching it, the vessels penetrate the embryonic tissues and eventually come into connection with the heart, which has already differentiated and has begun to beat before the connection with the vessels is made, so that when it is made the circulation is at once established. Before, however, the vascularization reaches the embryo some of the canals begin to enlarge (Fig.
131,-4), producing arteries and veins, the rest of the network forming capillaries uniting these two sets of vessels, and, this process continuing, there are eventually differentiated a single vitelline artery and two vitelline veins (Fig. 131, B).
In the human embryo the small size of the yolk-sac permits of the extension of the vascular area over its entire surface at an early period, and this condition has already been reached in the earliest stages known and consequently no sinus terminalis such as occurs in the rabbit is visible. Otherwise the conditions are probably similar to what has been described above, the first circulation developed being associated with the yolk-sac.
It is to be noted that the capillary network of the area vasculosa consists of relatively wide anastomosing spaces whose endothelial lining rests directly upon the substance islands (Fig. 130). In certain of the embryonic organs, notably the liver, the metanephros and the heart, the network has a similar character, consisting of wide anastomosing spaces bounded by an endothelium which rests directly, or almost so, upon the parenchyma of the organ (the hepatic cylinders, the mesonephric tubules, or the cardiac muscle trabecular) (Figs. 132 and 190, B). To this form of capillary the term sinusoid has been applied (Minot), and it appears to be formed by the expansion of the wall of a previously existing blood-vessel, which thus moulds itself, as it were, over the parenchyma of the organ. The
Fig. 130.  -  Surface View of a Portion of the Area Vasculosa of a Chick.
The vascular network is represented by the shaded portion. Bi, Bloodisland; Si, substance-island.  -  (Disse.)
true capillaries, on the other hand, are more definitely tubular in form, are usually imbedded in mesenchymatous connective tissue and are developed in the same manner as the primary capillaries of the area vasculosa, by the aggregation of vasifactive cells to form cords, and the subsequent hollowing out of these. Whether these vasifactive cells are new differentiations of the embryonic mesenchyme or are budded off from the walls of existing capillaries which have grown in from extra-embryonic regions, is at present undecided. The Formation of the Blood.  -  The mesamceboids, which are
i i
A , \
Fig. 131.  -  The Vascular Areas of Rabbit Embryos. In B the Veins are Represented by Black and the Network is Omitted.  -  (van Beneden and Julin.)
the first formed blood-corpuscles are all nucleated and destitute or nearly so of haemoglobin. They have been held by some observers to be the only source of the various forms of corpuscles that are found in the adult vessels, while others maintain that they give rise only to the red corpuscles, the leukocytes arising in tissues external to the blood-vessels and only secondarily making their way into them. According to this latter view the red and white corpuscles have a different origin and remain distinct throughout life.
So long as the formation of blood-vessels is taking place in the extra-embryonic mesoderm, so long are new mesamceboids being differentiated from the mesoderm. But whether the formation of blood-vessels within the embryo results from a differentiation of the embryonic mesoderm in situ, or from the actual ingrowth of vessels from the extra-embryonic regions (His), is as yet uncertain, and hence it is also uncertain whether mesamceboids are differentiated from the embryonic mesoderm or merely pass into the embryonic region from the more peripheral areas. However this may be, it is certain that they and the erythrocytes that are formed from them increase by division in the interior of the embryo, and that there are certain portions of the body in which these divisions take place most abundantly, partly, perhaps, on account of the more favorable conditions of nutrition which they present and partly because they are regions where the circulation is sluggish and permits the accumulation of erythrocytes. These regions constitute what have been termed the hematopoietic organs, and are especially noticeable in the later stages of fetal life, diminishing in number and variety about the time of birth. It must be remembered, however, that the life of individual corpuscles is comparatively short, their death and disintegration taking place continually during the entire life of the individual, so that there is a necessity for the formation of new corpuscles and for the existence of haematopoietic organs at all stages of life.
In the fetus mesamceboids in process of division may be found in the general circulation and even in the heart itself, but they are much more plentiful in places where the blood-pressure is diminished, as, for instance, in the larger capillaries of the lower limbs and in the capillaries of all the visceral organs and of the subcutaneous tissues. Certain organs, however, such as the liver, the spleen, and the bone-marrow, present especially favorable conditions for the multiplication of the blood-cells, and in these not only are the capillaries enlarged so as to afford resting-places for the corpuscles, but gaps appear in the walls of the vessels through which the blood-elements may pass and so come into intimate relations with the actual tissues is
of the organs (Fig. 132). After birth the haematopoietic function of the liver ceases and that of the spleen becomes limited to the formation of white corpuscles, though the complete function may be re-established in cases of extreme anaemia. The bone-marrow, however, retains the function completely, being throughout life the seat of formation of both red and white corpuscles, the lymphatic nodes and follicles, as well as the spleen, assisting in the formation of the latter elements.
The mesamceboids early become converted into nucleated red
corpuscles or erythrocytes by the development of haemoglobin in their cytoplasm, their nuclei at the same time becoming granular. Up to a stage at which the embryo has a length of about 12 mm. these are the only form of red corpuscle in the circulation, but at this time (Minot) a new form, characterized by its smaller size and more deeply staining nucleus, makes its appearance. These erythrocytes have been termed normoblasts (Ehrlich), although they are merely transition stages leading to the formation of erythroplastids by the extrusion of their nuclei (Fig. 133). The cast-off nuclei undergo degeneration and phagocytic absorption by the leukocytes, and the masses of cytoplasm pass into the circulation, becoming more and more numerous as development proceeds, until finally they are the typical haemoglobin-containing elements in the blood and form what are properly termed the red bloodcorpuscles.
It has already (p. 224) been pointed out that discrepant views
Fig. 132.  -  Section of a Portion or the Liver of a Rabbit Embryo of 5 mm. e, Erythrocytes in the liver substance and in a capillary; h, hepatic cells.  -  (van der Stricht)
prevail as to the origin of the white blood-corpuscles. Indeed, three distinct modes of origin have been assigned to them. According to one view they have a common origin with the erythrocytes from the mesamceboids (Weidenreich), according to another they are formed from mesenchyme cells outside the cavities of the blood-vessels (Maximo w), while according to a third view the first formed leukocytes take their origin from the endodermal epithelial cells of the thymus gland (Prenant).
But whatever may be their origin in later stages the leukocytes multiply by mitosis and there is a tendency for the dividing cells to collect in the lymphoid tissues, such as
the lymph nodes, tonsils, etc., to form /||\ /^s 0$\ /^p. & more or less definite groups which  -  ^^ v^ KjJ \Jj
have been termed germ-centers (Flem
. m , .. . . _ Fig. 133.  -  Stages in the
ming). The new cells when they first transformation of an Ery
pass into the circulation have a rel- throcyte into an _ Erythro
r plastid.  -  (van der Stricnt.)
atively large nucleus surrounded by a
small amount of cytoplasm without granules and, since they resemble the cells found in the lymphatic vessels, are termed lymphocytes (Fig. 134, a). In the circulation, however, other forms of leukocytes also occur, which are believed to have their origin from cells with much larger nuclei and more abundant cytoplasm, which occur throughout life in the bone-marrow and have been termed myelocytes. Cells of a similar type, free in the circulation, constitute what are termed the finely granular leukocytes (neutrophile cells of Ehrlich) (Fig. 134, b), but whether these and the myelocytes are derived from lymphocytes or have an independent origin is as yet undetermined. Less abundant are the coarsely granular leukocytes (eosinophile cells of Ehrlich) (Fig. 134, c), characterized by the coarseness and staining reactions of their cytoplasmic granules and by their reniform or constricted nucleus. They are probably derivatives of the finely granular type and it has been maintained by Weidenreich that their granules have been acquired by the phagocytosis of degenerated erythrocytes. Finally, a third type is formed by the polymorphonuclear or polynuclear leukocytes (basophile cells
of Ehrlich) (Fig. 134, d), which are to be regarded as leukocytes in the process of degeneration and are characterized by their irregularly lobed or fragmented nuclei, as well as by their staining peculiarities.
In the fetal haematopoietic organs and in the bone-marrow of the adult large, so-called giant-cells are found, which, although they do not enter into the general circulation, are yet associated with the development of the blood-corpuscles. These giant-cells as they
Fig. 134.  -  Figures of the Different Forms of White Corpuscles occurring
in Human Blood.
a, Lymphocytes; b, finely granular (neutrophile) leukocyte; c, coarsely granular (eosino
phile) leukocyte; d, polymorphonuclear (basophile) leukocyte.  -  (Weidenreich.)
occur in the bone-marrow are of two kinds which seem to be quite distinct, although both are probably formed from leukocytes. In one kind the cytoplasm contains several nuclei, wherce they have been termed polycaryocytes, and they seem to be the cells which have already been mentioned as osteoclasts (p. 158). In the other kind (Fig- I 35) tne nucleus is single, but it is large and irregular in shape, frequently appearing as if it were producing buds. These megacaryocytes appear to be phagocytic cells, having as their function the destruction of degenerated corpuscles and of the nuclei of the erythrocytes.
The blood-platelets have recently been shown by Wright to be formed from the cytoplasm of the megacaryocytes, by the constriction and separation of portions of the slender processes to which they give rise in their amoeboid movements (Fig. 135).
Fig. 135.  -  Megacaryocyte from a Kitten, which has Extended two pseudopodial processes through the wall of blood-vessel and is budding off blood-platelets.
bp, Blood-platelets; V, blood-vessel.  -  (J. H. Wright.)
The Formation of the Heart.  -  The heart makes its appearance while the embryo is still spread out upon the surface of the yolk-sac, and arises as two separate portions which only later come into contact in the median line. On each side of the body near the margins of the embryonic area a fold of the splanchnopleure appears, projecting into the ccelomic cavity, and within this fold a very thinwalled sac is formed, probably by a splitting off of its innermost cells (Fig. 136, .4). Each fold will produce a portion of the muscular walls (myocardium) of the heart, and each sac part of its endothelium (endocardium). As the constriction of the embryo from the yolk-sac proceeds, the two folds are gradually brought nearer together (Fig. 136, B), until they meet in the mid-ventral line, when the myocardial folds and endocardial sacs fuse together (Fig. 136, C) to form a cylindrical heart lying in the mid-ventral line of the body, in front of the anterior surface of the yolk-sac and in what will later be the
cervical region of the body. At an early stage the various veins which have already been formed, the vitellines, umbilicals, jugulars
Fig. 136.  -  Diagrams Illustrating the Formation or the Heart in the
Guinea-pig. The mesoderm is represented in black and the endocardium by a broken line. am, Amnion; en, endoderm; h, heart; i, digestive tract.-  -  (After Strahl and Carius.)
and cardinals, unite together to open into a sac-like structure, the sinus venosus, and this opens into the posterior end of the heart cylinder. The anterior end of the cylinder tapers off to form the
aortic bulb, which is continued forward on the ventral surface of the pharyngeal region and carries the blood away from the heart. The blood accordingly opens into the posterior end of the heart tube and flows out from its anterior end.
The simple cylindrical form soon changes, however, the heart tube in embryos of 2.15 mm. in length having become bent upon itself into a somewhat S-shaped curve (Fig. 137). Dorsally and to the left is the end into which the sinus venosus opens, and from this
Fig. 137.  -  Heart of EmbrycTof 2.15 mm., from a Reconstruction.
a, Atrium; ab, aortic bulb; d, diaphragm; dc, ductus Cuvieri; /, liver; v, ventricle; vj, jugular vein; vu, umbilical vein.  -  (His.)
Fig. 138.  -  Heart of Embryo of 4.2 mm., seen from the Dorsal Surface.
DC, Ductus Cuvieri; I A , left atrium rA, right atrium; vf, jugular vein; VI, left ventricle; vu, umbilical vein.  -  (His.)
the heart tube ascends somewhat and then bends so as to pass at first ventrally and then caudally and to the right, where it again bends at first dorsally and then anteriorly to pass over into the aortic bulb. The portion of the curve which lies dorsally and to the left is destined to give rise to both atria, the portion which passes from right to left represents the future left ventricle, while the succeeding portion represents the right ventricle. In later stages (Fig. 138) the left ventricular portion drops downward in front of the atrial
portion, assuming a more horizontal position, while the portion which represents the right ventricle is drawn forward so as to lie in the same plane as the left.
At the same time two small out-pouchings develop from the atrial part of the heart and form the first indications of the two atria. As development progresses, these increase in size to form large pouches opening into a common atrial canal (Fig. 139) which is directly continuous with the left ventricle, and as the enlargement of the pouches continues their openings into the canal enlarge,
until finally the pouches become continuous with one another, forming a single large sac, and the atrial canal becomes reduced to a short tube which is slightly invaginated into the ventricle (Fig. 140).
In the meantime the sinus venosus, which was originally an oval sac and opened into the atrial canal, has elongated transversely until it has assumed the form of a crescent whose convexity is in contact with the walls of the atria, and its opening into the heart has verged toward the right, until it is situated entirely within the area of the right atrium. As the enlargement of the atria continues, the right horn and median portion of the crescent are gradually taken up into their walls, so that the various veins which originally opened into the sinus now open directly into the right atrium by a single opening, guarded by a projecting fold which is continued upon the roof of the atrium as a muscular ridge known as the septum spurium (Fig. 140, sp). The left horn of the crescent is not taken up into the atrial wall, but remains upon its posterior surface as an elongated sac forming the coronary sinus.
The division of the now practically single atrial cavity into the
Fig. 139.  -  Heart of Embryo of 5 mm., Seen from in Front and slightly from Above.  -  (His).
permanent right and left atria begins with the formation of a falciform ridge running dorso-ventrally across the roof of the cavity. This is the atrial septum or septum primum (Fig. 140, ss), and it rapidly increases in size and thickens upon its free margin, which reaches almost to the upper border of the short atrial canal (Fig. 142). The continuity of the two atria is thus almost dissolved, but is soon re-established by the formation in the dorsal part of the septum of an opening which soon reaches a considerable size and is known as
Fig. 140.  -  Inner Surface of the Heart of an Embryo of 10 mm.
al, Atrio-ventricular thickening; sp, septum spurium; ss, septum primum; sv, septum
ventriculi; ve, Eustachian valve.  -  (His.)
the foramen ovale (Fig. 141, fo). Close to the atrial septum, and parallel with it, a second ridge appears in the roof and ventral wall of the right atrium. This septum secundum (Fig. 141, S 2 ) is of relatively slight development in the human embryo, and its free edge, arching around the ventral edge and floor of the foramen ovale, becomes continuous with the left lip of the fold which guards the opening of the sinus venosus and with this forms the annulus of Vieussens of the adult heart.
Si Sz
When the absorption of the sinus venosus into the wall of the right atrium has proceeded so far that the veins communicate directly with the atrium, the vena cava superior opens into it at the upper part of the dorsal wall, the vena cava inferior more laterally, and below this is the smaller opening of the coronary sinus. The
upper portion of the right lip of the fold which originally surrounded the opening of the sinus venosus, together with the septum spurium, gradually disappears; the lower portion persists, however, and forms (i) the Eustachian valve (Fig. 141, Ve), guarding the opening of the inferior cava and directing the blood entering by it toward the foramen ovale, and (2) the Thebesian valve, which guards the opening of the coronary sinus. At first no Fig. 141. -  Heart of Embryo veins communicate with the left atrium,
OF I0.2 CM. FROM WHICH HALF , 111 c t i 1
of the Right Auricle has but on the development of the lungs and been Removed. the establishment of their vessels, the
fo, Foramen ovale; pa, pul- , . .,,
monary artery; S u septum pri- pulmonary veins make connection with
mum; S 2 ,_ septum secundum; j t TwQ ye j ns arise from eac h l ung an( J ba, systemic aorta; V, right ven- °
tricle; vd and vcs, inferior and as they pass toward the heart they unite
superior venae cavae; Ve, Eusta- ,-, i r „ j •
chfan valve. . in pairs, the two vessels so formed again
uniting to form a single short trunk which opens into the upper part of the atrium (Fig. 142, Vep). As is the case with the right atrium and the sinus venosus, the expansion of the left atrium brings about the absorption of the short single trunk into its walls, and, the expansion continuing, the two vessels are also absorbed, so that eventually the four primary veins open independently into the atrium.
While the atrial septa have been developing there has appeared on the dorsal wall of the atrial canal a tubercle-like thickening of the endocardium, and a similar thickening also forms on the ventral wall. These endocardial cushions increase in size and finally unite together by their tips, forming a complete partition, dividing the
2 35
atrial canal into a right and left half (Fig. 142). With the upper edge of this partition the thickened lower edge of the atrial septum unites, so that the separation of the atria would be complete were it not for the foramen ovale.
Fig. 142.  -  Section through a Reconstruction of the Heart of a Rabbit
Embryo of 10. i mm. Ad and Ad u Right and As, left atrium; Bw x and Bw 2 , lower ends of the ridges which divide the aortic bulb; En, endocardial cushion; En.r and En.s, thickenings of the cushion; la, interatrial and Iv, interventricular communication; S v septum primum; Sd, right and Ss, left horn of the sinus venosus; S.iv, ventricular septum; SM, opening of the sinus venosus into the atrium; Vd, right and Vs, left ventricle; Vej, jugular vein; Vep, pulmonary vein; Vvd and Vvs, right and left limbs of the valve guarding the opening of the sinus venosus.  -  (Born.)
While these changes have been taking place in the atrial portion of the heart, the separation of the right and left ventricles has also been progressing, and in this two distinct septa take part. From the floor of the ventricular cavity along the line of junction of the
right and left portions a ridge, composed largely of muscular tissue, arises (Figs. 140 and 142), and, growing more rapidly in its dorsal than its ventral portion, it comes into contact and fuses with the dorsal part of the partition of the atrial canal. Ventrally, however, the ridge, known as the ventricular septum, fails to reach the ventral part of the partition , so that an oval foramen, situated just below the point where the aortic bulb arises, still remains between the two ventricles. This opening is finally closed by what it termed the aortic septum. This makes its appearance in the aortic bulb just at the point where the first lateral branches which give origin to the pulmonary arteries (see p. 243) arise, and is formed by the fusion of the free edges of two endocardial ridges which develop on opposite sides of the bulb. From its point of origin it gradually extends down the bulb until it reaches the ventricle, where it fuses with the free edge of the ventricular septum and so completes the separation of the two ventricles (Fig. 143). The bulb now consists of two vessels lying side by side, and owing to the position of the partition at its anterior end, one of these vessels, that which opens into the right ventricle, is continuous with the pulmonary arteries, while the other, which opens into the left ventricle, is continuous with the rest of the vessels which arise from the forward continuation of the bulb. As soon as the development of the partition is completed, two grooves, corresponding in position to the lines of attachment of the partition on the inside of the bulb, make their appearance on the outside and gradually deepen until they finally meet and divide the bulb into two separate vessels, one of which is the pulmonary aorta and the other the systemic aorta.
In the early stages of the heart's development the muscle bundles which compose the wall of the ventricle are very loosely arranged, so that the ventricle is a somewhat spongy mass of muscular tissue with a relatively small cavity. As development proceeds the bundles nearest the outer surface come closer together and form a compact layer, those on the inner surface, however, retaining their loose arrangement for a longer time (Fig. 142). The lower edge of the atrial canal becomes prolonged on the left side into one, and on the
right side into two, flaps which project downward into the ventricular cavity, and an additional flap arises on each side from the lower
Fig. 143.  -  Diagrams of Sections through the Heart of Embryo Rabbits to Show the Mode of Division of the Ventricles and of the Atrio-ventricular Orifice.
Ao, Aorta; Ar. p, pulmonary artery; B, aortic bulb; Bw 2 and *, one of the ridges which divide the bulb; Eo, and Eu, upper and lower thickenings of the margins of the atrio-ventricular orifice; F.av.c, the original atrio-ventricular orifice; F.av.d and F.av.s, right and left atrio-ventricular orifices; Oi, interventricular communication; S.iv, ventricular septum; Vd and Vs, right and left ventricles.  -  (Born.)
edge of the partition of the atrial canal, so that three flaps occur in the right atrio-ventricular opening and two in the left. To the
2 3 8
under surfaces of these flaps the loosely arranged muscular trabecular of the ventricle are attached, and muscular tissue also occurs in the flaps. This condition is transitory, however; the muscular tissue of the flaps degenerates to form a dense layer of connective tissue, and at the same time the muscular trabecular undergo a condensation. Some of them separate from the flaps, which represent the atrio-ventricular valves, and form muscle bundles which may fuse throughout their entire length with the more compact portions of the ventricular walls, or else may be attached only by their ends, forming loops; these two varieties of muscle bundles constitute the trabecule carnece of the adult heart. Other bundles
Fig. 144.  -  Diagrams showing the Development of the Atjriculo-ventricular
b, Muscular trabecule; cht, chordae tendinae; mk and vtk 1 , valve; pm, musculus papillaris;
tc, trabeculse carneae; v, ventricle.  -  (From Hertwig, after Gegenbaur.)
may retain a transverse direction, passing across the ventricular cavity and forming the so-called moderator bands; while others, again, retaining their attachment to the valves, condense only at their lower ends to form the musculi papillares, their upper portions undergoing conversion into strong though slender fibrous cords, the chorda tendinece (Fig. 144).
The endocardial lining of the ventricles is at first a simple sac separated by a distinct interval from the myocardium, but when the condensation of the muscle trabecular occurs the endocardium applies itself closely to the irregular surface so formed, dipping into all the crevices between the trabeculse carneae and wrapping itself around
the musculi papillares and chordae tendineae so as to form a complete
lining of the inner surface of the myocardium.
The aortic and pulmonary semilunar valves make their appearance,
before the aortic bulb undergoes its longitudinal splitting, as four
tubercle-like thickenings of connective tissue situated on the inner
wall of the bulb just where it arises from the ventricle. When the
division of the bulb occurs, two of the thickenings, situated on
opposite sides, are divided, so that both the
pulmonary and systemic aorta? receive three
thickenings (Fig. 145). Later the thickenings
become hollowed out on the surfaces directed
away from the ventricles and are so converted
into the pouch-like valves of the adult.
Changes in the Heart after Birth.  -  The T FlG - 145- -  Diagrams
/ . Illustrating the For
heart when first formed lies far forward in the mation of the Semi
neck region of the embryo, between the head £toarValves.-(G^«»and the anterior surface of the yolk-sac, and from this position it gradually recedes until it reaches its final position in the thorax. And not only does it thus change its relative position, but the direction of its axes also changes. For at an early stage the ventricles lie directly in front of (i. e., ventrad to) the atria and not below them as in the adult heart, and this primitive condition is retained until the diaphragm has reached its final position (see p. 322).
In addition to these changes in position, which are antenatal, important changes also occur in the atrial septum after birth. Throughout the entire period of fetal life the foramen ovale persists, permitting the blood returning from the placenta and entering the right atrium to pass directly across to the left atrium, thence to the left ventricle, and so out to the body through the systemic aorta (see p. 267). At birth the lungs begin to function and the placental circulation is cut off, so that the right atrium receives only venous blood and the left only arterial; a persistence of the foramen ovale beyond this period would be injurious, since it would permit of a mixture of the arterial and venous bloods, and, consequently, it
closes completely soon after birth. The closure is made possible by the fact that during the growth of the heart in size the portion of the atrial septum which is between the edge of the foramen ovale and the dorsal wall of the atrium increases in width, so that the foramen is carried further and further away from the dorsal wall of the atrium and comes to be almost completely overlapped by the annulus of Vieussens (Fig. 141). This process continuing, the dorsal portion of the atrial septum finally overlaps the free edge of the annulus, and after birth the fusion of the.overlapping surfaces takes place and the foramen is completely closed.
In a large percentage (25 to 30 per cent.) of individuals the fusion of the surfaces of the septum and annulus is not complete, so that a slit-like opening persists between the two atria. This, however, does not allow of any mingling of the blood in the two cavities, since when the atria contract the pressure of the blood on both sides will force the overlapping folds together and so practically close the opening. Occasionally the growth of the dorsal portion of the septum is imperfect or is inhibited, in which case closure of the foramen ovale is impossible.
The Development of the Arterial System.-  -  It has been seen (p. 221) that the formation of the blood-vessels begins in the extraembryonic splanchnic mesoderm surrounding the yolk-sac and extends thence toward the embryo. Furthermore, it has been seen that the vessels appear as capillary networks from which definite stems are later elaborated. This seems also to be the method of formation of the vessels developed within the body of the embryo, the arterial and venous stems being first represented by a number of anastomosing capillaries, from which, by the enlargement of some and the disappearance of the others, the definite stems are formed.
The earliest known embryo that shows a blood circulation is that described by Eternod (Fig. 43). From the plexus of vessels on the yolk-sack two veins arise which unite with two other veins returniDg from the chorion by the belly-stalk and passing forward to the heart as the two umbilical veins (Fig. 146, Vu). There is as yet no vitelline vein, the chorionic circulation in the human embryo apparently taking precedence over the vitelline. From the heart a short arterial stem arises, which soon divides so as to form three
branches* passing dorsally on either side of the pharynx. The branches of each side then unite to form a paired dorsal aorta (dAr, dAs) which extends caudally and is continued into the belly-stalk and so to the chorion as the umbilical arteries (Au). There is as yet no sign of vitelline arteries passing to the yolk-sack, again an indication of the subservience of the vitelline to the chorionic circulation in the human embryo.
Fig. 146.  -  Diagram showing the Arrangement of the Blood-vessels in an
Embryo 1.3 mm. in Length.
Au, Umbilical artery; All, allantois; Ch, chorionic villus; dAr and dAs, right and left
dorsal aortae; Vu, umbilical veins; Ys, yolk-sack.  -  (From Kollmann after Eternod.)
In later stages when the branchial arches have appeared the dorsally directed arteries are seen to lie in these, forming what are termed the branchial arch vessels, and later also the two dorsal
* Evans (Keibel-Mall, Human Embryology, Vol. 11, 1912) considers two of these branches to be probably plexus formations rather than definite stems, since there is evidence to indicate that only one such stem exists at such an early stage of development. 16
aortae fuse as far forward as the region of the eighth cervical segment to form a single trunk from which segmental branches arise.
It will be convenient to consider first the history of the vessels which pass dorsally in the branchial arches. Altogether, six of these vessels are developed, the fifth being rudimentary and transitory, and when fully formed they have an arrangement which may be understood from the diagram (Fig. 147). This arrangement represents a condition which is permanent in the lower vertebrates. In the fishes the respiration is performed by means of gills developed upon the branchial arches, and the heart is an organ which receives venous blood from the body and pumps it to the gills, in which it becomes arterialized and is then collected into the dorsal aortae, which distribute it to the body. But in terrestrial animals, with the loss of the gills and the development of the lungs as respiratory organs, the capillaries of the gills disappear and the afferent and efferent branchial vessels become continuous, the condition represented in the diagram resulting. But this condition is merely temporary in the mammalia and numerous changes occur in the arrangement of the vessels before the adult plan is realized. The first change is a disappearance of the vessel of the first arch, the ventral stem from which it arose being continued forward to form the temporal arteries, giving off near the point where the branchial vessel originally arose a branch which represents the internal maxillary artery in part, and possibly also a
Fig. 147.  -  Diagram Illustrating the Primary Arrangement of the Branchial Arch Vessels.
a, aorta; db, aortic bulb; ec, external carotid; ic, internal carotid; sc, subclavian; I-VI, branchial arch vessels.
second branch which represents the external maxillary (His). A little later the second branchial vessel also degenerates (Fig. 148), a branch arising from the ventral trunk near its former origin, possibly representing the future lingual artery (His), and then the portion of the dorsal trunk which intervenes between the third and fourth branchial vessels vanishes, so that the dorsal trunk anterior to the third branchial arch is cut off from its connection with the dorsal aorta and forms, together with the vessel of the third arch, the internal carotid, while the ventral trunk, anterior to the point of
Fig. 148.  -  Arteriat, System of an Embryo of 10 mm.
Ic, Internal carotid; P, pulmonary artery; Ve, vertebral artery; III to VI, persistent
branchial vessels.  -  (His.)
origin of the third vessel, becomes the external carotid, and the portion which intervenes between the third and fourth vessels becomes the common carotid (Fig. 149).
The rudimentary fifth vessel, like the first and second, disappears, but the fourth persists to form the aortic arch, there being at this stage of development two complete aortic arches. From the sixth vessel a branch arises which passes backward to the lungs, forming the pulmonary artery, and the portion of the vessel of the right side which intervenes between this and the aortic arch disappears, while the corresponding portion of the left side persists
until after birth, forming the ductus arteriosus (ductus Botalli) (Fig. 149). When the longitudinal division of the aortic bulb occurs (p. 236), the septum is so arranged as to place the sixth arch in communication with the right ventricle and the remaining vessels in connection with the left ventricle, the only direct communication
between the systemic and ec pulmonary vessels being by
way of the ductus arteriosus, whose significance will be explained later (p. 267).
One other change is still necessary before the vessels acquire the arrangement which they possess during fetal life, and this consists in the disappearance of the lower portion of the right aortic arch (Fig. 149), so that the left arch alone forms the connection between the heart and the dorsal aorta. The upper part of the right aortic arch persists to form the proximal part of the right subclavian artery, the portion of the ventral trunk which unites the arch with the aortic bulb becoming the innominate artery.
From the entire length of the thoracic aorta, and in the embryo from the aortic arches, lateral branches arise corresponding to each segment and accompanying the segmental nerves. The first of these branches arises just below the point of union of the vessel of the sixth arch with the dorsal trunk and accompanies the hypoglossal nerve (Fig. 150, h), and that which accompanies the seventh
Fig. 149.  -  Diagram Illustrating the changes in the branchial arch vessels.
a, Aorta; da, ductus arteriosus; ec, external carotid; ic, internal carotid; pa, pulmonary artery; sc, subclavian; I- VI, aortic arch vessels.
cervical nerve arises just above the point of union of the two aortic arches (Fig. 150, s), and extends out into the limb bud, forming the subclavian artery.*
Further down twelve pairs of lateral branches, arising from the thoracic portion of the aorta, represent the intercostal arteries, and still lower four pairs of lumbar arteries are formed, the fifth lumbars being represented by two large branches, the common iliacs, which seem from their size to be the continuations of the aorta rather than branches of it. The true continuation of the aorta is, however, the middle sacral artery, which represents in a degenerated form the caudal prolongation of the aorta of other mammals, and, like this, gives off lateral branches corresponding to the sacral segments.
In addition to the segmental FlG . I50 . -  diagram showing the Re
lateral branches arising from nations op the Lateral Branches to
the Aortic Arches.
the aorta, Visceral branches, EC> External carotid; h, lateral branch
Which have their origin rather cacompanying the hypoglossal nerve; IC,
° internal carotid; ICo, intercostal; IM, m
from the Ventral surface, also ternal mammary; s, subclavian; v, verte
^„„,,~ TV, ~™u„mr, ~t - mm bral; I to VIII, lateral cervical branches;
OCCUr. In embryos of 5 mm. I; 2) lateral thoracic branches.
these branches are arranged in
a segmental manner in threes, a median unpaired vessel passing to the digestive tract and a pair of more lateral branches passing to the mesonephros (see p. 339) corresponding to each of the paired branches passing to the body wall (Fig. 151). As
* It must be remembered that the right subclavian of the adult is more than equivalent to the left, since it represents the fourth branchial vessel + a portion of the dorsal longitudinal trunk + the lateral segmental branch (see Fig. 142).
development proceeds the great majority of these visceral branches disappear, certain of the lateral ones persisting, however, to form the renal, internal spermatic, and hypogastric arteries of the adult, while the unpaired branches are represented only by the c celiac artery and the superior and inferior mesenteries. The superior mesenteric artery is the adult representative of the vitelline artery of the embryo and arises from the aorta by two, three or more roots, which correspond to the fifth, fourth and higher thoracic
Fig. 151.  -  Diagram showing the Arrangement of the Segmental Branches
arising from the aorta. A, Aorta; B, lateral somatic branch; c, lateral visceral branch; D, median visceral
branch; E, peritoneum.
segments. Later, all but the lowest of the roots disappear and the persisting one undergoes a downward migration in accordance with the recession of the diaphragm and viscera (see p. 322), until in embryos of 17 mm. it lies opposite the first lumbar segment. Similarly the cceliac and inferior mesenteric arteries, which when first recognizable in embryos of 9 mm. correspond with the fourth and twelfth thoracic segments respectively, also undergo a secondary downward migration, the cceliac artery in embryos of 17 mm. arising
opposite the twelfth thoracic and the inferior mesenteric opposite the third lumbar segment.
The umbilical arteries of the embryo seem at first to be the direct continuations of the dorsal aortas (Fig. 146), but as development proceeds they come to arise from the aorta opposite the third lumbar segment, where they are in line with the lateral visceral segmental branches. They pass ventral to the Wolffian duct (see p. 339) and are continued out along with the allantois to the chorionic villi. Later this original stem is joined, not far from its origin, by what appears to be the lateral somatic branch of the fifth lumbar segment, whereupon the proximal part of the original umbilical vessel degenerates and the umbilical comes to arise from the somatic branch, which is the common iliac artery of adult anatomy (Fig. 152). Hence it is that this vessel in the adult gives origin both to branches such as the external iliac, the gluteal, the sciatic and the internal pudendal, which are distributed to the body walls
or their derivatives, and to others, such as the vesical, inferior haemorrhoidal and uterine, which are distributed to the pelvic viscera. At birth the portions of the umbilical arteries beyond the umbilicus are severed when the umbilical cord is cut, and their intra-embryonic portions, which have been called the hypogastric arteries, quickly undergo a reduction in size. Their proximal portions remain functional as the superior vesical arteries, carrying blood to the urinary bladder, but the portions which intervene between the
Fig. 152.  -  Diagram Illustrating the Development of the Umbilical Arteries.