Development of the Brain in Vertebrates | Ectodermal Organs | Embryology

We will first trace the features manifest in the development of the brain in all vertebrates and then point out some of the peculiarities found in higher vertebrates, especially in mammals and in man.

The anterior brain vesicle, the prosencephalon, gives rise at its anterior end to the telencephalon. The latter produces in an early stage two bulges directed anterolaterally which become the cerebral hemispheres. Each bulge of the telencephalon contains a pocket-like cavity, which is an extension of the original cavity of the anterior brain vesicle (prosencephalon).

The two cavities are known as the lateral ventricles of the brain. Originally, they are in broad communica­tion with the rest of the cavity of the prosencephalon, but later the channels leading into the lateral ventricles may become constricted. These channels are called the interven­tricular foramina (also known as the foramina of Monro).

The cerebral hemispheres grow out forward beyond the original anterior end of the prosencephalon. The median strip of the anterior wall of the prosencephalon persists in a relatively unchanged state as the lamina terminalis.

The telencephalon in lower vertebrates is the primary center of the olfactory sense and is intimately connected with the olfactory organs which develop immediately anterior and lateral to it. The nerve fibers growing out from the sensory cells in the olfactory organs penetrate into the telencephalon near its anterior end, in a part which differentiates as the olfactory lobe.

Being primarily a center for the olfactory sense, the telencephalon shows the same kind of dependence on the olfactory organ as the spinal nerves and the spinal cord show in respect to the peripheral organs to which they are connected. This has been shown by removing the olfactory rudiments and by trans­planting additional ones.

In the absence of an olfactory organ, the corresponding lobe of the forebrain remains underdeveloped. If an additional olfactory organ is transplanted into the region beside the normal one, the fibers of the olfactory nerve grow from the transplanted organ into the adjoining lobe of the forebrain, and this causes an increase in the size of the latter.

In the lower groups of vertebrates, the walls of the cerebral hemispheres are only moderately thickened, and the nerve cells remain accumulated on the inner surface of the walls, that is, on the surface facing the internal cavity.

In the higher vertebrates, starting with the reptiles, the outward migration of nerve cells is not restricted to the mantle surrounding the cavity of the brain, but the migrating cells penetrate beyond the layer of nerve fibers which make up the white matter originally surrounding the gray matter and accumulate near the surface, giving rise to the cortex of the cerebral hemispheres.

The diencephalon in all vertebrates is remarkable in that it produces a great variety of structures with different functions, in addition to the two eye vesicles, which will be referred to later. The brain cavity in the region of the diencephalon remains fairly large and is known as the third ventricle of the brain.

The cells in the brain wall become concentrated mainly in the sides of the diencephalon which become thickened and are known as the optic thalamus. The thickening is continued here until the inner surfaces of both sides meet in the middle, forming what is called the commissura mollis. The optic thalamus is primarily an association center, which increases in importance in higher vertebrates.

The greater part of the dorsal wall, which we may refer to as the roof of the diencephalon, becomes membranous and later does not contain any nerve cells at all. Instead it is richly supplied with blood vessels and becomes the choroid plexus, which later bulges down into the cavity of the third ventricle.

The choroid plexus is the pathway by which nutrition and oxygen are brought into the ventricles of the brain. Processes of the choroid plexus may penetrate from the third ventricle into the lateral ventricles by way of the foramina of Monro.

Only the posterior section of the roof of the diencephalon retains the nervous character, but parts of it form dorsally directed outgrowths, of which the most important are the parietal organ and the pineal body. Both are formed as rather long, finger-like outgrowths of the brain roof, the end sections of which become transformed into more or less rounded masses of cells, while the stalks become constricted and may even be interrupted later.

In lower vertebrates, either the pineal body (in some frog tadpoles), or the parietal organ (in reptiles), or both (in cyclostomes) become eyelike organs, but in higher vertebrates they differentiate as glandular structures. The homologies and the function of these structures have been the subject of many investi­gations, but in neither respect has a clear answer as yet been given.

Both organs develop mid-dorsally, that is, at the site where the neural folds fused at an earlier stage, thus raising the question of whether the presumptive material of each organ is contained in one of the neural folds or in both. It has been found that at least in the case of the pineal body there are originally two rudiments, one on each edge of the neural plate, and that after neurulation these two rudiments fuse into one single unpaired organ.

The floor of the diencephalon produces in all vertebrates a funnel-like depression, the infundibulum. Part of the wall of the latter becomes segregated from the brain wall and fused with an outgrowth from the stomodeal invagination, the two together forming the hypophysis or pituitary gland, the most important endocrine gland in vertebrates.

The walls of the diencephalon on the sides and posterior to the infundibulum differentiate as another important nerve center, the hypothalamus, which is the center controlling, through the autonomic system, the vegetative functions of the body.

The midbrain remains a fairly simply organized part of the brain. The walls of the midbrain become thickened mainly ventrally, but the lateral walls and the roof are also fairly thick, and the latter gives rise to an important nerve center, the tectum. The cavity of the midbrain becomes narrow and is known as the aqueduct of Sylvius. In the lower vertebrates, fishes and amphibians, the tectum serves as the primary center of the visual organ, and the nerve fibers entering the brain from the eyes end here.

Beginning with the anuran amphibians, however, the posterior part of the tectum acquires connections with nerve fibers coming in from the ear, and in the amniotes the tectum develops four thickenings, the corpora quadrigemina, of which the two anterior thickenings are concerned with the sense of vision, while the two posterior ones are related to the sense of hearing.

Just as the hemispheres of the telencephalon are related to the olfactory organ, the tectum of the midbrain, in lower vertebrates, is related to the eyes and is dependent in its differentiation on the nerve fibers entering the midbrain from the eyes. In amphibians and fishes, the optic tectum fails to develop normally and remains thinner than usual if the eye rudiment is removed or reduced in size in an early stage.

The ventrolateral parts of the midbrain show some resemblance to the ventrolateral plates of the spinal cord, inasmuch as they contain groups of motor cells which send out processes forming two pairs of motor nerves, the third (oculomotor) and the fourth (trochlear) cranial nerves.

In mammals, the ventrolateral parts of the mesen­cephalon are much enlarged, owing to the number of nerve fibers passing through this part of the mesencephalon on the way from the cerebral hemispheres to the medulla and the spinal cord. These thickened parts are known as the cerebral peduncles.

The neural tube may be fairly straight or only slightly curved at the time of its formation, but in later stages it becomes bent at an angle at one or more levels. These bends are known as flexures. The most important flexure, and the one found consis­tently in all vertebrates, is that at the level of the midbrain, known as the cephalic flexure. Here the foremost part of the brain (the telencephalon and the diencephalon) is bent downward in front of the anterior tip of the notochord.

The rhombencephalon gives rise to the metencephalon and the medulla oblon­gata. The cavity of the rhombencephalon expands especially anteriorly, just behind the midbrain, and becomes the fourth ventricle. The roof of the medulla thins out and is converted into a second choroid plexus, the posterior choroid plexus, which is similar to the one developed from the roof of the diencephalon.

The future nerve cells are concentrated lateroventrally in the floor of the medulla but are separated into two masses by a median groove. This arrangement of nervous tissue gives the medulla a very characteristic appearance.

In spite of differences in gross configuration, the rhombencephalon in its internal organization shows an unmistakable similarity to the spinal cord. A ventral floor plate extends along the whole length of the rhombencephalon, forming a median groove, the median sulcus.

On the sides of the rhombencephalon a lateral groove is clearly indicated which is an extension of the limiting groove of the spinal cord. This groove subdivides the mass of tissue on each side into a ventrolateral plate and a dorsolateral plate. Owing to the expansion of the membranous roof of the rhombencephalon, the dorsolateral plate lies lateral rather than dorsal to the ventrolateral plate.

The rhombencephalon, as indicated before, gives rise to the metencephalon and the medulla oblongata. The metencephalon in a younger embryo is no more than a slightly thickened section at the anterior end of the medulla (which in higher vertebrates gives rise to the pons Varolii) and a transverse bar in the roof of the brain, just behind the mesencephalon and anterior to the choroid plexus of the fourth ventricle.

The dorsolateral part of the metencephalon, corresponding to the dorsolateral plate of the spinal cord, gives rise to the cerebellum. The cerebellum, although a mid-dorsal organ in its final form, develops from two swellings of the brain tissue to the right and left of the anterior end of the membranous roof of the fourth ventricle.

The development of the cerebellum starts rather late. In the human embryo, the growth of the cerebellar rudiments begins during the second month of pregnancy. At two months the swellings are very distinct, though still separate.

Later the two swellings fuse, producing the vermis of the cerebellum in the midline, while the lateral parts become the hemispheres. As in the telencephalon, the nerve cells migrate in the cerebellum from their place of origin near the cavity of the brain toward the external surface, producing the cortex of the cerebellum.

In the medulla, the main mass of gray matter lies adjacent to the fourth ventricle. Here are situated the centers of the cranial nerves entering and leaving the medulla. At its posterior end, the medulla gradually merges into the spinal cord.

The membranous part of the roof becomes narrower and eventually disappears, and the medioventral groove becomes deeper and is directly continued as the central canal of the spinal cord, while the dorsolateral plates converge and fuse dorsally over the canal.

The development of the brain in higher vertebrates can best be illustrated by a brief description of the changes which the brain rudiment undergoes in the human embryo.

The brain of the human embryo toward the end of the first month after conception is not very different from the brain of an amphibian embryo, except that it is distinctly more elongated. The eye rudiments are separated from the prosencepha­lon, and the cephalic flexure is indicated, but there is, as yet, no trace of the progressive development of the hemispheres of the forebrain or the cerebellum.

Soon after the beginning of the second month after conception, the telencephalon forms a conspicuous bulge dorsally in front of the eye rudiments. The bulge is slightly bilobed, the first indication of the future hemispheres of the brain. The cephalic flexure is increased to such an extent that the brain appears to be bent on itself. In addition to the cephalic flexure, the brain now shows two more flexures.

At the level of the anterior part of the rhombencephalon, the brain is bent with the convexity facing downward, forming the pontine flexure. The metencephalon with the pons Varolii (after which the flexure is named) lies in front of the flexure, and most of the medulla remains posterior to the flexure. A third flexure, with the convexity facing dorsally (the same as the cephalic flexure), appears at the junction between the medulla and the spinal cord. It is called the cervical flexure.

About the middle of the second month after conception, the flexures of the brain become much more distinct, especially the pontine flexure. The development of the cerebellum has not progressed much, but the midbrain enlarges considerably and attains its largest relative size. The main advance, however, is shown by the telencepha­lon. The two lobes (indicated previously) enlarge greatly and spread out forward, upward, and backward, partially covering the laterodorsal surfaces of the diencephalon.

By the beginning of the third month after conception, the hemispheres of the telencephalon constitute, by far, the greatest part of the brain. They have expanded backward to such an extent that they almost completely cover the diencepha­lon.

A broad shallow groove on the outer surface of each hemisphere (the future lateral fissure) indicates the separation of the temporal lobe of the brain. The mesencephalon is greatly expanded dorsally and forms a large mass posterior to the cerebral hemispheres.

The cerebellum is the last part of the brain to become conspicuous on inspection from the outside, since the rudiments of the cerebellum are formed originally as masses of brain tissue bulging into the fourth ventricle from the sides of the metencephalon. These masses increase and later fuse together above the cavity of the brain, and only after this does the rudiment of the cerebellum swell to the exterior of the fourth ventricle. This occurs toward the third month after conception.

At four months after conception, the cerebral hemispheres have grown so large that they cover the midbrain from the sides and touch the cerebellar hemispheres, which by this time have become clearly discernible. Even at this time the surface of the cerebral hemisphere, apart from the lateral fissure, is quite smooth, but during the second half of the period of pregnancy the surface becomes wrinkled and folded, giving rise to the characteristic gyri of the human brain.