SEGMENTATION.

Immediately after its formation the zygote is separated, by a series of consecutive mitotic divisions, into a large number of cells which are grouped together in the form of a solid spherical mass, called a morula on account of the mulberrylike appearance of its surface. This period of division is called the period of segmentation (Figs. 24-27).

Polar bodies

The segmentation divisions are of the homotype form, and there is evidence which tends to the conclusion that the earliest divisions, by which the zygote is divided first into two and then into four parts, are quantitatively and qualitatively equal. After a time, however, the divisions result in the formation of cells of different sizes and different capabilities, definite and circumscribed functions being allocated to certain groups of cells and their descendants. It is probable FIG. 24.-SEGMENTATION OF ZYGOTE that at this time cells are set apart which are the progenitors of the germ cells of the next generation, and which therefore retain all the capabilities of their ancestors. These cells are the means by which the species is reproduced and the hereditary tendencies are transmitted from generation to generation. At the same time other cells are set apart for the production of the tissues and organs of the individual which will be produced from the zygote, and in which the germ cells and their descendants will be lodged and protected till they attain their maturity.

Oolemma

Polar bodies

4-Cell Stage.

After the morula is established one of the first FIG. 25.-SEGMENTATION OF ZYGOTE definite changes which occurs in its constitution is the differentiation of its cells into an outer layer and an inner mass (Fig. 26).

Oolemma

In the human subject, as in many other mammals, Outer layer the cells of the outer layer constitute the trophoblast or trophoblastic ectoderm, which plays a most important part in the nutrition of the embryo and foetus. It enters into the formation of the chorion, or outermost envelope of the growing zygote, which is subsequently differentiated into a placental and a nonplacental portion and which serves, in the first instance, both as a protective and a nutritive covering. In many mammals the cells of the inner mass soon separate into two main the ecto-mesoderm groups, and the entoderm; but it appears probable that, in the human subject, they differentiate into three groups, ecto-mesoderm, primary mesoderm, and entoderm.

Trophoblast

Entoderm

Primary mesoderm

FIG. 27.-DIFFERENTIATION OF

In the majority of mammals, immediately before or as the differentiation of the inner mass occurs, a cavity appears in the zygote. As soon as the cavity appears the morula is converted into a blastula and the cavity enlarges until it separates the inner mass from the outer layer, except at one pole of the zygote, where the inner mass and the outer layer remain in contact. The cavity is called the segmentation cavity. would appear, however, from the evidence at present available, that this primitive cavity never exists in the human subject, for as the main part of the inner mass separates from the outer layer the cells of the primary mesoderm segment of the inner mass proliferate rapidly and form a jelly-like tissue which completely fills the space which would otherwise become the segmentation cavity. At the same time the ecto-mesodermal and entodermal segments of the

It ZYGOTE AND CELLS (Hypothetical).

inner mass become converted into hollow vesicles by the appearance of cavities in their interiors (Fig. 29).

When the above-mentioned changes have occurred the zygote consists of three spheres, one large and two small. The large sphere is bounded by the tropho

Trophoblast

Amniotic
ectoderm

Primary mesoderm

blast; it contains the two small spheres and the jelly-like mass of primary mesoderm derived from the primary mesoderm segment of the inner mass (Fig. 29).

The two small vesicles lie ex-centrically in the interior of the larger vesicle. The larger and more external of the two is the ecto-mesodermal vesicle. It is separated from the trophoblast, peripherally, and the entodermal vesicle, centrally, by the surrounding primary mesoderm.

The early appearance of the mesoderm in the FIG. 28.—FURTHER DIFFERENTIATION Zygote and its insinuation at so early a period between the ectoderm and the entoderm are peculiarities limited to the human subject. In most mammals

OF ZYGOTE (Hypothetical).

the mesoderm does not appear until the embryonic area and its primitive streak are defined.

The Embryonic Area. The area where the two inner vesicles lie in apposition with each other is the region of the zygote from which the embryo will be formed; it is called, therefore, the embryonic area, and at the time of its definition it consists of three layers, ectoderm, primary mesoderm, and entoderm. It is uncertain whether the mesoderm which is present in the area at this period takes part in the formation of the embryo or is replaced at a later period by mesoderm derived from the cells of the

(Peter's Ovum).

ecto-mesodermal vesicle; the latter certainly forms a large part of the mesoderm of the embryo. The Extra- Embryonic Colom. The extra-embryonic coelom is a space which appears as two clefts, one on each side of the embryonic area, in the primary mesoderm (Fig. 30). The clefts fuse together round the periphery of the embryonic area, and the single space so formed expands rapidly until the mesoderm which originally filled the greater part of the larger vesicle becomes converted into a thin layer which lines the inner surface of the trophoblast and covers the outer surfaces of the epithelial walls of the extra-embryonic parts of the two inner vesicles (Fig. 32).

The extra-embryonic celom does not extend into the embryonic area, and it never completely separates the ecto-mesodermal vesicle from the inner surface of the trophoblast; on the contrary, the primary mesoderm on the outer surface of the ecto-mesodermal vesicle retains its continuity with the mesoderm on the inner surface of the trophoblast until the termination of intrauterine life, and

it takes part, as will be seen later, in the formation of the umbilical cord, which connects the foetus with the placenta (p. 54).

The Differentiation of the Embryonic Area. As the embryonic area is the area of contact between the ecto-mesodermal and the entodermal vesicles it is, at first, circular in outline. As growth continues the area becomes oval, and a linear streak, the primitive streak, appears in that part of the oval which becomes the posterior part of the area (Fig. 31).

At the same time the position of the mesodermal elements of the wall of the ecto-mesodermal vesicle is revealed, for the primitive streak is a thickened ridge of cells which grows from the ecto-mesoderm and projects against the entoderm in the posterior part of the embryonic area, pushing aside the primitive mesoderm which intervened between the adjacent parts of the walls of the ecto-mesodermal and the entodermal vesicles. The deeper cells of the ridge, those next the entoderm, are the mesodermal elements of the primitive ecto-mesoderm, and, by proliferation, they form the larger part, if not the whole, of the embryonic mesoderm and also an organ, called the notochord. The mesoderm produced from the primitive streak may be termed the secondary mesoderm.

Immediately after the formation of the primitive streak a groove, the neural groove, appears in the anterior

part of the embryonic area. It is formed by the longi

Mesoderm of amnion

tudinal folding of a thickened Chorion.
plate of ectoderm, the neural
plate, which is the rudiment
of the whole of the central
and peripheral portions of the
nervous system, except per-
haps the olfactory nerves, and
the end organs of the sensory
nerves. From it also are de-
rived the cells of the primitive
sheaths of the nerve-fibres
and the chromaffin cells of the
supra-renal glands and other
chromaffin bodies.

Ectoderm of amnion
Neurenteric canal

A

B

C

The lateral walls of the FIG. 31.-SCHEMA OF DORSAL SURFACE OF EMBRYONIC AREA OF neural groove are called the

neural folds.

ZYGOTE AFTER THE REMOVAL OF PART OF THE CHORION AND
PART OF THE AMNION.

Their

Almost from the first the anterior ends of the neural folds are united together a short distance posterior to the anterior end of the embryonic area. posterior ends, which remain separate for a time, embrace the anterior part of the primitive streak. In the meantime, however, a groove, the primitive groove, has appeared on the surface of the primitive streak. The anterior end of the primitive groove deepens, until it forms a perforation which passes, through the anterior end of the streak and the subjacent entoderm, into the cavity of the entodermal vesicle. As this perforation passes from the floor of the posterior part of the neural groove into that part of the entodermal vesicle which afterwards becomes the primitive enteron or alimentary canal, it is called the neurenteric canal. The neurenteric canal is but a transitory passage, and it disappears in man and other mammals before the neural groove is converted into a closed neural tube.

After the appearance of the primitive groove and the neurenteric canal the posterior ends of the neural folds converge, across the anterior part of the primitive streak and groove, and fuse together posterior to the neurenteric canal. The primitive streak is thus divided into two portions. (1) An anterior portion, which lies at first in the floor of the neural groove, and, later, in the floor or ventral wall of the posterior end of the spinal medulla; and (2) a posterior portion, which remains on the surface and takes part in the formation of the median portion of the posterior end of the body, forming the perineum, and the median part of the ventral wall of the body, from the perineum to the umbilicus. It is through the

perineal section of the posterior part of the primitive streak that, at a later period of embryonic life, the anal and urogenital orifices of the body are formed.

The Formation of the Notochord and the Secondary [blast Mesoderm.-The notochord and the secondary mesoderm are formed from the primitive streak; the notochord from its anterior extremity, and the secondary mesoderm from its lateral

Extra-embryonic coelom margins and posterior end.

Plasmodial trophoblast
Cellular trophoblast
Mesoderm lining of
trophoblast

-Chorion

Extra-embryonic cœlom

Mesoderm of amnion

Ectoderm of amnion

Amnion cavity Mesoderm covering entoderm

As soon as the primitive streak is established its anterior end becomes a node or centre of growth by means of which the length and, to a certain extent, the breadth of the body are increased. The portion of the body formed by the activity of the anterior end of the streak is the dorsal portion, from the back part of the roof of the nose, anteriorly, to the posterior end of the trunk. The perineum and the ventral wall of the body, from the perineum to the umbilicus, are formed from the posterior part of the primitive streak. Nevertheless, the primitive streak undergoes little or no increase in length; indeed, as growth continues, it becomes relatively shorter as contrasted with the total length of the embryonic region, for the new material, formed by its borders and its anterior extremity, is transformed into the tissues of embryo as rapidly as it is created.

The Notochord.-The notochord or primitive skeletal axis is formed by the proliferation of cells from the anterior end of the primitive streak. On its first appearance it is a narrow process of cells, the head process, which projects forwards from the anterior boundary of the neurenteric canal, between the ectoderm and the entoderm. Shortly after its appearance the head process wedges its way between the entoderm cells, and from that period onwards, as the posterior parts are formed, by continued proliferation from the front end of the primitive streak, they are at once intercalated in the dorsal wall of the entodermal sac, where they remain, forming a part of the dorsal wall of the entodermal cavity (Fig. 33), for a

Cavity of entodermal vesicle

FIG. 34.-SCHEMA OF TRANSVERSE SECTION OF ZYGOTE ALONG

considerable time. At a later period the notochordal cells are excalated from the entoderm, and then they form a cylindrical rod of cells which occupies the median plane, lying between the floor of the ectodermal neural groove and the entodermal roof of the primitive alimentary canal, which, in the meantime, has been more or less moulded off from the dorsal part of the entodermal sac (Fig. 37). For a still longer time the caudal end of the notochord remains connected with the anterior end of the primitive streak, and its cephalic end is continuous with the entoderm of a small portion of the embryonic area, which lies immediately in front of the anterior end of the neural groove and which becomes bilaminar by the disappearance of the primary mesoderm. This region, because it afterwards forms the boundary membrane between the anterior end of the primitive entodermal canal and the primitive buccal cavity or stomatodæum, is called the bucco-pharyngeal membrane (Fig. 55, p. 42). It disappears about the third week of embryonic life, and immediately afterwards the anterior end of the notochord separates from the entoderm, but the posterior end remains continuous with the primitive streak, until the formation of the neural tube is completed.

After a time the cylindrical notochordal rod is surrounded by secondary mesoderm which becomes converted into the vertebral column of the adult. As the vertebral column is formed the notochord is enlarged in the regions of the intervertebral fibro-cartilages and for a time assumes a nodulated appearance (Fig. 60).

Ultimately the notochord disappears, as a distinct structure, but remnants of it are believed to exist as the pulpy centres of the intervertebral fibro-cartilages. The extension of the notochord into the region of the head is of interest from a morphological, and possibly also from a practical point of view. It extends through the base of the cranium from the anterior border of the foramen magnum into the posterior part of the body of the sphenoid bone. Its presence in the posterior part of the skull suggests that that region was, primitively, of vertebral nature. As the notochord passes through the occipital portion of the skull it pierces the basilar portion of the occipital region first from within outwards and then in the reverse direction. It lies, therefore, for a short distance, on the ventral surface of the rudiment of the occipital bone, in the dorsal wall of the pharynx, and it is possible that some of the tumours which form in the dorsal wall of the pharynx are due to the proliferation of remnants of its pharyngeal portion.

The Differentiation of the Secondary Mesoderm.-It has already been noted that a portion of the inner mass of the human zygote becomes converted directly into mesoderm which may be called, for convenience, primary mesoderm. It was stated also that the wall of the larger of the two inner vesicles of the zygote consists of ecto-mesoderm, that term being intended to convey the idea that the cells of the wall of the larger inner vesicle were the progenitors of both ectodermal and mesodermal cells.

As soon as the larger of the two inner vesicles is formed two areas of its wall are defined: (1) the part in contact with the smaller inner or entodermal vesicle and (2) the remainder. As future events prove, the cells of the larger area, which is not in contact with the entodermal vesicle, simply produce ectodermal descendants which line the inner surface of a sac-like covering of the embryo termed the amnion; they are, therefore, the predecessors of the amniotic ectoderm.

The cells of the larger inner vesicle, which lie adjacent to the smaller entoderm vesicle, and are merely separated from the entoderm by a thin layer of primary mesoderm, take part in the formation of the embryo; forming, with the entoderm, the embryonic area from which the embryo is evolved. These cells are the forerunners of both ectoderm and mesoderm, and as the mesoderm developed from them is differentiated after the formation of the primary mesoderm it may be termed secondary mesoderm or primitive streak mesoderm; the latter term being applied because it is differentiated in a linear region called the primitive streak (p. 23). It is the formation and fate of this primitive streak mesoderm which is now to be considered.

At first the embryonic area is circular in outline, at a later period it becomes ovoid, and in the narrower or caudal portion of the ovoid area a linear thickening