The Neural Groove and Tube

FIG. 17– Human embryo—length, 2 mm. Dorsal view, with the amnion laid open. X 30. (After Graf Spee.) )

In front of the primitive streak two longitudinal ridges, caused by a folding up of the ectoderm, make their appearance, one on either side of the middle line  These are named the neural folds; they commence some little distance behind the anterior end of the embryonic disk, where they are continuous with each other, and from there gradually extend backward, one on either side of the anterior end of the primitive streak. Between these folds is a shallow median groove, the neural groove). The groove gradually deepens as the neural folds become elevated, and ultimately the folds meet and coalesce in the middle line and convert the groove into a closed tube, the neural tube or canal , the ectodermal wall of which forms the rudiment of the nervous system. After the coalescence of the neural folds over the anterior end of the primitive streak, the blastopore no longer opens on the surface but into the closed canal of the neural tube, and thus a transitory communication, the neurenteric canal, is established between the neural tube and the primitive digestive tube. The coalescence of the neural folds occurs first in the region of the hind-brain, and from there extends forward and backward; toward the end of the third week the front opening (anterior neuropore) of the tube finally closes at the anterior end of the future brain, and forms a recess which is in contact, for a time, with the overlying ectoderm; the hinder part of the neural groove presents for a time a rhomboidal shape, and to this expanded portion the term sinus rhomboidalis has been applied . Before the neural groove is closed a ridge of ectodermal cells appears along the prominent margin of each neural fold; this is termed the neural crest or ganglion ridge, and from it the spinal and cranial nerve ganglia and the ganglia of the sympathetic nervous system are developed. By the upward growth of the mesoderm the neural tube is ultimately separated from the overlying ectoderm.	1
FIG. 18– Chick embryo of thirty-three hours’ incubation, viewed from the dorsal aspect. X 30. (From Duval’s “Atlas d’Embryologie.”) )
The cephalic end of the neural groove exhibits several dilatations, which, when the tube is closed, assume the form of three vesicles; these constitute the three primary cerebral vesicles, and correspond respectively to the future fore-brain (prosencephalon), mid-brain (mesencephalon), and hind-brain (rhombencephalon) . The walls of the vesicles are developed into the nervous tissue and neuroglia of the brain, and their cavities are modified to form its ventricles. The remainder of the tube forms the medulla spinalis or spinal cord; from its ectodermal wall the nervous and neuroglial elements of the medulla spinalis are developed while the cavity persists as the central canal.

Segmentation of the Fertilized Ovum

The early segmentation of the human ovum has not yet been observed, but judging from what is known to occur in other mammals it may be regarded as certain that the process starts immediately after the ovum has been fertilized, i. e., while the ovum is in the uterine tube. The segmentation nucleus exhibits the usual mitotic changes, and these are succeeded by a division of the ovum into two cells of nearly equal size. The process is repeated again and again, so that the two cells are succeeded by four, eight, sixteen, thirty-two, and so on, with the result that a mass of cells is found within the zona striata, and to this mass the term morula is applied . The segmentation of the mammalian ovum may not take place in the regular sequence of two, four, eight, etc., since one of the two first formed cells may subdivide more rapidly than the other, giving rise to a three-or a five-cell stage. The cells of the morula are at first closely aggregated, but soon they become arranged into an outer or peripheral layer, the trophoblast, which does not contribute to the formation of the embryo proper, and an inner cell-mass, from which the embryo is developed. Fluid collects between the trophoblast and the greater part of the inner cell-mass, and thus the morula is converted into a vesicle, the blastodermic vesicle . The inner cell-mass remains in contact, however, with the trophoblast at one pole of the ovum; this is named the embryonic pole, since it indicates the situation where the future embryo will be developed. The cells of the trophoblast become differentiated into two strata: an outer, termed the syncytium or syncytiotrophoblast, so named because it consists of a layer of protoplasm studded with nuclei, but showing no evidence of subdivision into cells; and an inner layer, the cytotrophoblast or layer of Langhans, in which the cell outlines are defined. As already stated, the cells of the trophoblast do not contribute to the formation of the embryo proper; they form the ectoderm of the chorion and play an important part in the development of the placenta. On the deep surface of the inner cell-mass a layer of flattened cells, the entoderm, is differentiated and quickly assumes the form of a small sac, the yolk-sac. Spaces appear between the remaining cells of the mass and by the enlargement and coalescence of these spaces a cavity, termed the amniotic cavity  is gradually developed. The floor of this cavity is formed by the embryonic disk composed of a layer of prismatic cells, the embryonic ectoderm, derived from the inner cell-mass and lying in apposition with the entoderm.    1 )       The Primitive Streak; Formation of the Mesoderm.—The embryonic disk becomes oval and then pear-shaped, the wider end being directed forward. Near the narrow, posterior end an opaque streak, the primitive streak ( and , makes its appearance and extends along the middle of the disk for about one-half of its length; at the anterior end of the streak there is a knob-like thickening termed Hensen’s knot. A shallow groove, the primitive groove, appears on the surface of the streak, and the anterior end of this groove communicates by means of an aperture, the blastophore, with the yolk-sac. The primitive streak is produced by a thickening of the axial part of the ectoderm, the cells of which multiply, grow downward, and blend with those of the subjacent entoderm  From the sides of the primitive streak a third layer of cells, the mesoderm, extends lateralward between the ectoderm and entoderm; the caudal end of the primitive streak forms the cloacal membrane.    2     The extension of the mesoderm takes place throughout the whole of the embryonic and extra-embryonic areas of the ovum, except in certain regions. One of these is seen immediately in front of the neural tube. Here the mesoderm extends forward in the form of two crescentic masses, which meet in the middle line so as to enclose behind them an area which is devoid of mesoderm. Over this area the ectoderm and entoderm come into direct contact with each other and constitute a thin membrane, the buccopharyngeal membrane, which forms a septum between the primitive mouth and pharynx. In front of the buccopharyngeal area, where the lateral crescents of mesoderm fuse in the middle line, the pericardium is afterward developed, and this region is therefore designated the pericardial area. A second region where the mesoderm is absent, at least for a time, is that immediately in front of the pericardial area. This is termed the proamniotic area, and is the region where the proamnion is developed; in man, however, a proamnion is apparently never formed. A third region is at the hind end of the embryo where the ectoderm and entoderm come into apposition and form the cloacal membrane.    3   The blastoderm now consists of three layers, named from without inward: ectoderm, mesoderm, and entoderm; each has distinctive characteristics and gives rise to certain tissues of the body.     4   FIG. 15– Series of transverse sections through the embryonic disk of Tarsius. (After Hubrecht.) Section I passes through the disk, in front of Hensen’s knot and shows only the ectoderm and entoderm. Sections II, III, and IV pass through Hensen’s knot, which is seen in V tapering away into the primitive streak. In III, IV, and V the mesoderm is seen springing from the keel-like thickening of the ectoderm, which in III and IV is observed to be continuous into the entoderm. )     Ectoderm.—The ectoderm consists of columnar cells, which are, however, somewhat flattened or cubical toward the margin of the embryonic disk. It forms the whole of the nervous system, the epidermis of the skin, the lining cells of the sebaceous, sudoriferous, and mammary glands, the hairs and nails, the epithelium of the nose and adjacent air sinuses, and that of the cheeks and roof of the mouth. From it also are derived the enamel of the teeth, and the anterior lobe of the hypophysis cerebri, the epithelium of the cornea, conjunctiva, and lacrimal glands, and the neuro-epithelium of the sense organs.    5   Entoderm.—The entoderm consists at first of flattened cells, which subsequently become columnar. It forms the epithelial lining of the whole of the digestive tube excepting part of the mouth and pharynx and the terminal part of the rectum (which are lined by involutions of the ectoderm), the lining cells of all the glands which open into the digestive tube, including those of the liver and pancreas, the epithelium of the auditory tube and tympanic cavity, of the trachea, bronchi, and air cells of the lungs, of the urinary bladder and part of the urethra, and that which lines the follicles of the thyroid gland and thymus.    6 FIG. 16– A series of transverse sections through an embryo of the dog. (After Bonnet.) Section I is the most anterior. In V the neural plate is spread out nearly flat. The series shows the uprising of the neural folds to form the neural canal. a. Aortæ. c. Intermediate cell mass. ect. Ectoderm. ent. Entoderm. h, h. Rudiments of endothelial heart tubes. In III, IV, and V the scattered cells represented between the entoderm and splanchnic layer of mesoderm are the vasoformative cells which give origin in front, according to Bonnet, to the heart tubes, h; l.p. Lateral plate still undivided in I, II, and III; in IV and V split into somatic (sm) and splanchnic (sp) layers of mesoderm. mes. Mesoderm. p. Pericardium. so. Primitive segment)     Mesoderm.—The mesoderm consists of loosely arranged branched cells surrounded by a considerable amount of intercellular fluid. From it the remaining tissues of the body are developed. The endothelial lining of the heart and blood-vessels and the blood corpuscles are, however, regarded by some as being of entodermal origin.    7   As the mesoderm develops between the ectoderm and entoderm it is separated into lateral halves by the neural tube and notochord, presently to be described. A longitudinal groove appears on the dorsal surface of either half and divides it into a medial column, the paraxial mesoderm, lying on the side of the neural tube, and a lateral portion, the lateral mesoderm. The mesoderm in the floor of the groove connects the paraxial with the lateral mesoderm and is known as the intermediate cell-mass; in it the genito-urinary organs are developed. The lateral mesoderm splits into two layers, an outer or somatic, which becomes applied to the inner surface of the ectoderm, and with it forms the somatopleure; and an inner or splanchnic, which adheres to the entoderm, and with it forms the splanchnopleure . The space between the two layers of the lateral mesoderm is termed the celom.    8 Note 5.  In the mammalian ova the nutritive yolk or deutoplasm is small in amount and uniformly distributed throughout the cytoplasm; such ova undergo complete division during the process of segmentation, and are therefore termed holoblastic. In the ova of birds, reptiles, and fishes where the nutritive yolk forms by far the larger portion of the egg, the cleavage is limited to the formative yolk, and is therefore only partial; such ova are termed meroblastic. Again, it has been observed, in some of the lower animals, that the pronuclei do not fuse but merely lie in apposition. At the commencement of the segmentation process the chromosomes of the two pronuclei group themselves around the equator of the nuclear spindle and then divide; an equal number of male and female chromosomes travel to the opposite poles of the spindle, and thus the male and female pronuclei contribute equal shares of chromatin to the nuclei of the two cells which result from the subdivision of the fertilized ovum. ]   The mode of formation of the germ layers in the human ovum has not yet been observed; in the youngest known human ovum (viz., that described by Bryce and Teacher), all three layers are already present and the mesoderm is split into its two layers. The extra-embryonic celom is of considerable size, and scattered mesodermal strands are seen stretching between the mesoderm of the yolk-sac and that of the chorion. ]

Fertilization of the Ovum

Fertilization consists in the union of the spermatozoön with the mature ovum . Nothing is known regarding the fertilization of the human ovum, but the various stages of the process have been studied in other mammals, and from the knowledge so obtained it is believed that fertilization of the human ovum takes place in the lateral or ampullary part of the uterine tube, and the ovum is then conveyed along the tube to the cavity of the uterus—a journey probably occupying seven or eight days and during which the ovum loses its corona radiata and zona striata and undergoes segmentation. Sometimes the fertilized ovum is arrested in the uterine tube, and there undergoes development, giving rise to a tubal pregnancy; or it may fall into the abdominal cavity and produce an abdominal pregnancy. Occasionally the ovum is not expelled from the follicle when the latter ruptures, but is fertilized within the follicle and produces what is known as an ovarian pregnancy. Under normal conditions only one spermatozoön enters the yolk and takes part in the process of fertilization. At the point where the spermatozoön is about to pierce, the yolk is drawn out into a conical elevation, termed the cone of attraction. As soon as the spermatozoön has entered the yolk, the peripheral portion of the latter is transformed into a membrane, the vitelline membrane which prevents the passage of additional spermatozoa. Occasionally a second spermatozoön may enter the yolk, thus giving rise to a condition of polyspermy: when this occurs the ovum usually develops in an abnormal manner and gives rise to a monstrosity. Having pierced the yolk, the spermatozoön loses its tail, while its head and connecting piece assume the form of a nucleus containing a cluster of chromosomes. This constitutes the male pronucleus, and associated with it there are a centriole and centrosome. The male pronucleus passes more deeply into the yolk, and coincidently with this the granules of the cytoplasm surrounding it become radially arranged. The male and female pronuclei migrate toward each other, and, meeting near the center of the yolk, fuse to form a new nucleus, the segmentation nucleus, which therefore contains both male and female nuclear substance; the former transmits the individualities of the male ancestors, the latter those of the female ancestors, to the future embryo. By the union of the male and female pronuclei the number of chromosomes is restored to that which is present in the nuclei of the somatic cells.   1

The SpermatozoönThe spermatozoa or male germ cells are developed in the testes and are present in enormous numbers in the seminal fluid. Each consists of a small but greatly modified cell. The human spermatozoön possesses a head, a neck, a connecting piece or body, and a tail (Fig. 6). 1 FIG. 6– Human spermatozoön. Diagrammatic. A. Surface view. B. Profile view. In C the head, neck, and connecting piece are more highly magnified. (See enlarged image) The head is oval or elliptical, but flattened, so that when viewed in profile it is pear-shaped. Its anterior two-thirds are covered by a layer of modified protoplasm, which is named the head-cap. This, in some animals, e. g., the salamander, is prolonged into a barbed spear-like process or perforator, which probably facilitates the entrance of the spermatozoön into the ovum. The posterior part of the head exhibits an affinity for certain reagents, and presents a transversely striated appearance, being crossed by three or four dark bands. In some animals a central rodlike filament extends forward for about two-thirds of the length of the head, while in others a rounded body is seen near its center. The head contains a mass of chromatin, and is generally regarded as the nucleus of the cell surrounded by a thin envelope. 2 The neck is less constricted in the human spermatozoön than in those of some of the lower animals. The anterior centriole, represented by two or three rounded particles, is situated at the junction of the head and neck, and behind it is a band of homogeneous substance. 3 The connecting piece or body is rod-like, and is limited behind by a terminal disk. The posterior centriole is placed at the junction of the body and neck and, like the anterior, consists of two or three rounded particles. From this centriole an axial filament, surrounded by a sheath, runs backward through the body and tail. In the body the sheath of the axial filament is encircled by a spiral thread, around which is an envelope containing mitochondria granules, and termed the mitochondria sheath. 4 The tail is of great length, and consists of the axial thread or filament, surrounded by its sheath, which may contain a spiral thread or may present a striated appearance. The terminal portion or end-piece of the tail consists of the axial filament only. 5 FIG. 7– Scheme showing analogies in the process of maturation of the ovum and the development of the spermatids (young spermatozoa). (See enlarged image) Krause gives the length of the human spermatozoön as between 52μ and 62μ, the head measuring 4 to 5μ, the connecting piece 6μ, and the tail from 41μ to 52μ. 6 By virtue of their tails, which act as propellers, the spermatozoa are capable of free movement, and if placed in favorable surroundings, e. g., in the female passages, will retain their vitality and power of fertilizing for several days. In certain animals, e. g., bats, it has been proved that spermatozoa retained in the female passages for several months are capable of fertilizing. 7 The spermatozoa are developed from the primitive germ cells which have become imbedded in the testes, and the stages of their development are very similar to those of the maturation of the ovum. The primary germ cells undergo division and produce a number of cells termed spermatogonia, and from these the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two spermatids or young spermatozoa; from this it will be seen that a primary spermatocyte gives rise to four spermatozoa. On comparing this process with that of the maturation of the ovum (Fig. 7) it will be observed that the primary spermatocyte gives rise to two cells, the secondary spermatocytes, and the primary oöcyte to two cells, the secondary oöcyte and the first polar body. Again, the two secondary spermatocytes by their subdivision give origin to four spermatozoa, and the secondary oöcyte and first polar body to four cells, the mature ovum and three polar bodies. In the development of the spermatozoa, as in the maturation of the ovum, there is a reduction of the nuclear chromosomes to one-half of those present in the primary spermatocyte. But here the similarity ends, for it must be noted that the four spermatozoa are of equal size, and each is capable of fertilizing a mature ovum, whereas the three polar bodies are not only very much smaller than the mature ovum but are incapable of further development, and may be regarded as abortive ova. 8The spermatozoa or male germ cells are developed in the testes and are present in enormous numbers in the seminal fluid. Each consists of a small but greatly modified cell. The human spermatozoön possesses a head, a neck, a connecting piece or body, and a tail (Fig. 6). 1 FIG. 6– Human spermatozoön. Diagrammatic. A. Surface view. B. Profile view. In C the head, neck, and connecting piece are more highly magnified. (See enlarged image) The head is oval or elliptical, but flattened, so that when viewed in profile it is pear-shaped. Its anterior two-thirds are covered by a layer of modified protoplasm, which is named the head-cap. This, in some animals, e. g., the salamander, is prolonged into a barbed spear-like process or perforator, which probably facilitates the entrance of the spermatozoön into the ovum. The posterior part of the head exhibits an affinity for certain reagents, and presents a transversely striated appearance, being crossed by three or four dark bands. In some animals a central rodlike filament extends forward for about two-thirds of the length of the head, while in others a rounded body is seen near its center. The head contains a mass of chromatin, and is generally regarded as the nucleus of the cell surrounded by a thin envelope. 2 The neck is less constricted in the human spermatozoön than in those of some of the lower animals. The anterior centriole, represented by two or three rounded particles, is situated at the junction of the head and neck, and behind it is a band of homogeneous substance. 3 The connecting piece or body is rod-like, and is limited behind by a terminal disk. The posterior centriole is placed at the junction of the body and neck and, like the anterior, consists of two or three rounded particles. From this centriole an axial filament, surrounded by a sheath, runs backward through the body and tail. In the body the sheath of the axial filament is encircled by a spiral thread, around which is an envelope containing mitochondria granules, and termed the mitochondria sheath. 4 The tail is of great length, and consists of the axial thread or filament, surrounded by its sheath, which may contain a spiral thread or may present a striated appearance. The terminal portion or end-piece of the tail consists of the axial filament only. 5 FIG. 7– Scheme showing analogies in the process of maturation of the ovum and the development of the spermatids (young spermatozoa). (See enlarged image) Krause gives the length of the human spermatozoön as between 52μ and 62μ, the head measuring 4 to 5μ, the connecting piece 6μ, and the tail from 41μ to 52μ. 6 By virtue of their tails, which act as propellers, the spermatozoa are capable of free movement, and if placed in favorable surroundings, e. g., in the female passages, will retain their vitality and power of fertilizing for several days. In certain animals, e. g., bats, it has been proved that spermatozoa retained in the female passages for several months are capable of fertilizing. 7 The spermatozoa are developed from the primitive germ cells which have become imbedded in the testes, and the stages of their development are very similar to those of the maturation of the ovum. The primary germ cells undergo division and produce a number of cells termed spermatogonia, and from these the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two spermatids or young spermatozoa; from this it will be seen that a primary spermatocyte gives rise to four spermatozoa. On comparing this process with that of the maturation of the ovum (Fig. 7) it will be observed that the primary spermatocyte gives rise to two cells, the secondary spermatocytes, and the primary oöcyte to two cells, the secondary oöcyte and the first polar body. Again, the two secondary spermatocytes by their subdivision give origin to four spermatozoa, and the secondary oöcyte and first polar body to four cells, the mature ovum and three polar bodies. In the development of the spermatozoa, as in the maturation of the ovum, there is a reduction of the nuclear chromosomes to one-half of those present in the primary spermatocyte. But here the similarity ends, for it must be noted that the four spermatozoa are of equal size, and each is capable of fertilizing a mature ovum, whereas the three polar bodies are not only very much smaller than the mature ovum but are incapable of further development, and may be regarded as abortive ova. 8

The spermatozoa or male germ cells are developed in the testes and are present in enormous numbers in the seminal fluid. Each consists of a small but greatly modified cell. The human spermatozoön possesses a head, a neck, a connecting piece or body, and a tail (Fig. 6).	1
FIG. 6– Human spermatozoön. Diagrammatic. A. Surface view. B. Profile view. In CSee enlarged image) the head, neck, and connecting piece are more highly magnified. (
The head is oval or elliptical, but flattened, so that when viewed in profile it is pear-shaped. Its anterior two-thirds are covered by a layer of modified protoplasm, which is named the head-cap. This, in some animals, e. g., the salamander, is prolonged into a barbed spear-like process or perforator, which probably facilitates the entrance of the spermatozoön into the ovum. The posterior part of the head exhibits an affinity for certain reagents, and presents a transversely striated appearance, being crossed by three or four dark bands. In some animals a central rodlike filament extends forward for about two-thirds of the length of the head, while in others a rounded body is seen near its center. The head contains a mass of chromatin, and is generally regarded as the nucleus of the cell surrounded by a thin envelope.	2
The neck is less constricted in the human spermatozoön than in those of some of the lower animals. The anterior centriole, represented by two or three rounded particles, is situated at the junction of the head and neck, and behind it is a band of homogeneous substance.	3
The connecting piece or body is rod-like, and is limited behind by a terminal disk.posterior centriole is placed at the junction of the body and neck and, like the anterior, consists of two or three rounded particles. From this centriole an axial filament, surrounded by a sheath, runs backward through the body and tail. In the body the sheath of the axial filament is encircled by a spiral thread, around which is an envelope containing mitochondria granules, and termed the mitochondria sheath. The	4
The tail is of great length, and consists of the axial thread or filament, surrounded by its sheath, which may contain a spiral thread or may present a striated appearance. The terminal portion or end-piece of the tail consists of the axial filament only.	5
FIG. 7– Scheme showing analogies in the process of maturation of the ovum and the development of the spermatids (young spermatozoa). (See enlarged image)
Krause gives the length of the human spermatozoön as between 52μ and 62μ, the head measuring 4 to 5μ, the connecting piece 6μ, and the tail from 41μ to 52μ.	6
By virtue of their tails, which act as propellers, the spermatozoa are capable of free movement, and if placed in favorable surroundings, e. g., in the female passages, will retain their vitality and power of fertilizing for several days. In certain animals, e. g., bats, it has been proved that spermatozoa retained in the female passages for several months are capable of fertilizing.	7
The spermatozoa are developed from the primitive germ cells which have become imbedded in the testes, and the stages of their development are very similar to those of the maturation of the ovum. The primary germ cells undergo division and produce a number of cells termed spermatogonia, and from these the primary spermatocytessecondary spermatocytes,spermatids or young spermatozoa; from this it will be seen that a primary spermatocyte gives rise to four spermatozoa. On comparing this process with that of the maturation of the ovum (Fig. 7) it will be observed that the primary spermatocyte gives rise to two cells, the secondary spermatocytes, and the primary oöcyte to two cells, the secondary oöcyte and the first polar body. Again, the two secondary spermatocytes by their subdivision give origin to four spermatozoa, and the secondary oöcyte and first polar body to four cells, the mature ovum and three polar bodies. In the development of the spermatozoa, as in the maturation of the ovum, there is a reduction of the nuclear chromosomes to one-half of those present in the primary spermatocyte. But here the similarity ends, for it must be noted that the four spermatozoa are of equal size, and each is capable of fertilizing a mature ovum, whereas the three polar bodies are not only very much smaller than the mature ovum but are incapable of further development, and may be regarded as abortive ova. are derived. Each primary spermatocyte divides into two and each secondary spermatocyte into two	8

The Animal Cell

All the tissues and organs of the body originate from a microscopic structure (the fertilized ovum), which consists of a soft jelly-like material enclosed in a membrane and containing a vesicle or small spherical body inside which are one or more denser spots. This may be regarded as a complete cell. All the solid tissues consist largely of cells essentially similar to it in nature but differing in external form.	4
In the higher organisms a cell may be defined as “a nucleated mass of protoplasm of microscopic size.” Its two essentials, therefore, are: a soft jelly-like material, similar to that found in the ovum, and usually styled cytoplasm, and a small spherical body imbedded in it, and termed a nucleus. Some of the unicellular protozoa contain no nuclei but granular particles which, like true nuclei, stain with basic dyes. The other constituents of the ovum, viz., its limiting membrane and the denser spot contained in the nucleus, called the nucleolus, are not essential to the type cell, and in fact many cells exist without them.	5
Cytoplasm (protoplasm) is a material probably of variable constitution during life, but yielding on its disintegration bodies chiefly of proteid nature. Lecithin and cholesterin are constantly found in it, as well as inorganic salts, chief among which are the phosphates and chlorides of potassium, sodium, and calcium. It is of a semifluid, viscid consistence, and probably colloidal in nature. The living cytoplasm appears to consist of a homogeneous and structureless ground-substance in which are embedded granules of various types. The mitochondria are the most constant type of granule and vary in form from granules to rods and threads. Their function is unknown. Some of the granules are proteid in nature and probably essential constituents; others are fat, glycogen, or pigment granules, and are regarded as adventitious material taken in from without, and hence are styled cell-inclusions or paraplasm. When, however, cells have been “fixed” by reagents a fibrillar or granular appearance can often be made out under a high power of the microscope. The fibrils are usually arranged in a network or reticulum, to which the term spongioplasm is applied, the clear substance in the meshes being termed hyaloplasm. The size and shape of the meshes of the spongioplasm vary in different cells and in different parts of the same cell. The relative amounts of spongioplasm and hyaloplasm also vary in different cells, the latter preponderating in the young cell and the former increasing at the expense of the hyaloplasm as the cell grows. Such appearances in fixed cells are no indication whatsoever of the existence of similar structures in the living, although there must have been something in the living cell to give rise to the fixed structures. The peripheral layer of a cell is in all cases modified, either by the formation of a definite cell membrane as in the ovum, or more frequently in the case of animal cells, by a transformation, probably chemical in nature, which is only recognizable by the fact that the surface of the cell behaves as a semipermeable membrane.	6
FIG. 1– Diagram of a cell. (Modified from Wilson.) (See enlarged image)
Nucleus.—The nucleus is a minute body, imbedded in the protoplasm, and usually of a spherical or oval form, its size having little relation to that of the cell. It is surrounded by a well-defined wall, the nuclear membrane; this encloses the nuclear substance (nuclear matrix), which is composed of a homogeneous material in which is usually embedded one or two nucleoli. In fixed cells the nucleus seems to consist of a clear substance or karyoplasm and a network or karyomitome. The former is probably of the same nature as the hyaloplasm of the cell, but the latter, which forms also the wall of the nucleus, differs from the spongioplasm of the cell substance. It consists of fibers or filaments arranged in a reticular manner. These filaments are composed of a homogeneous material known as linin, which stains with acid dyes and contains embedded in its substance particles which have a strong affinity for basic dyes. These basophil granules have been named chromatin or basichromatin and owe their staining properties to the presence of nucleic acid. Within the nuclear matrix are one or more highly refracting bodies, termed nucleoli, connected with the nuclear membrane by the nuclear filaments. They are regarded as being of two kinds. Some are mere local condensations (“net-knots”) of the chromatin; these are irregular in shape and are termed pseudo-nucleoli; others are distinct bodies differing from the pseudo-nucleoli both in nature and chemical composition; they may be termed true nucleoli, and are usually found in resting cells. The true nucleoli are oxyphil, i.e., they stain with acid dyes.	7
Most living cells contain, in addition to their protoplasm and nucleus, a small particle which usually lies near the nucleus and is termed the centrosome. In the middle of the centrosome is a minute body called the centriole, and surrounding this is a clear spherical mass known as the centrosphere. The protoplasm surrounding the centrosphere is frequently arranged in radiating fibrillar rows of granules, forming what is termed the attraction sphere.	8
Reproduction of Cells.—Reproduction of cells is effected either by direct or by indirect division. In reproduction by direct division the nucleus becomes constricted in its center, assuming an hour-glass shape, and then divides into two. This is followed by a cleavage or division of the whole protoplasmic mass of the cell; and thus two daughter cells are formed, each containing a nucleus. These daughter cells are at first smaller than the original mother cell; but they grow, and the process may be repeated in them, so that multiplication may take place rapidly. Indirect division or karyokinesis (karyomitosis) has been observed in all the tissues—generative cells, epithelial tissue, connective tissue, muscular tissue, and nerve tissue. It is possible that cell division may always take place by the indirect method.	9
The process of indirect cell division is characterized by a series of complex changes in the nucleus, leading to its subdivision; this is followed by cleavage of the cell protoplasm. Starting with the nucleus in the quiescent or resting stage, these changes may be briefly grouped under the four following phases (Fig. 2).	10
1. Prophase.—The nuclear network of chromatin filaments assumes the form of a twisted skein or spirem, while the nuclear membrane and nucleolus disappear. The convoluted skein of chromatin divides into a definite number of V-shaped segments or chromosomes. The number of chromosomes varies in different animals, but is constant for all the cells in an animal of any given species; in man the number is given by Flemming and Duesberg as twenty-four. 2 Coincidently with or preceding these changes the centriole, which usually lies by the side of the nucleus, undergoes subdivision, and the two resulting centrioles, each surrounded by a centrosphere, are seen to be connected by a spindle of delicate achromatic fibers the achromatic spindle. The centrioles move away from each other—one toward either extremity of the nucleus—and the fibrils of the achromatic spindle are correspondingly lengthened. A line encircling the spindle midway between its extremities or poles is named the equator, and around this the V-shaped chromosomes arrange themselves in the form of a star, thus constituting the mother star or monaster.	11
2. Metaphase.—Each V-shaped chromosome now undergoes longitudinal cleavage into two equal parts or daughter chromosomes, the cleavage commencing at the apex of the V and extending along its divergent limbs.	12
3. Anaphase.—The daughter chromosomes, thus separated, travel in opposite directions along the fibrils of the achromatic spindle toward the centrioles, around which they group themselves, and thus two star-like figures are formed, one at either pole of the achromatic spindle. This constitutes the diaster. The daughter chromosomes now arrange themselves into a skein or spirem, and eventually form the network of chromatin which is characteristic of the resting nucleus.	13
4. Telophase.—The cell protoplasm begins to appear constricted around the equator of the achromatic spindle, where double rows of granules are also sometimes seen. The constriction deepens and the original cell gradually becomes divided into two new cells, each with its own nucleus and centrosome, which assume the ordinary positions occupied by such structures in the resting stage. The nuclear membrane and nucleolus are also differentiated during this phase.	14