Development of the central nervous system

Spinal ganglia and meninges

Unlike the previously discussed neurons and macroglia of the spinal cord, the dorsal root ganglia (DRG) and unipolar neurons in the spinal ganglia originate from cells of the neural crest. Parts of these cells extend via the spinal nerves to somatic and visceral structures. Here, they provide various types of receptors for acquisition of sensory signals. The central processes of these cells, the dorsal roots of the spinal nerves, project into the spinal cord and assist in transmitting these signals to the brain for interpretation.

The primordial meninges form from the mesenchyme that surrounds the neural tube. The outer layer becoming the dura mater and the inner layer (originating from neural crest cells) becoming the leptomeninges, the arachnoid mater and pia mater. By the fifth week of development, cerebrospinal fluid (CSF) begins to form.

Spinal nerves and vertebral levels

At week eight of gestation, the embryonic spinal cord spans the entire length of vertebral canal, and the spinal nerves pass through the intervertebral foramina at the exact level that they emerge from the cord. Due to different growth rates, however, this relationship does not last: the embryo grows faster than the cord, and with this continued growth the caudal end of the cord becomes shorter and shorter compared to the length of the embryo.

By 24 weeks, the spinal cord stops at the first sacral vertebra (S1); which causes the end of the cord to rest around the second or third lumbar vertebrae (L2, L3) in a newborn infant. By adulthood, the cord stops at the lower border of the first lumbar vertebra (L1). Because of this length disparity, the spinal nerve roots in the lumbar and sacral cord project obliquely from the spinal cord to their corresponding vertebral levels below. The nerve roots at the end of the spinal cord form the conus medullaris, with the nerves branching out inferiorly to form the cauda equina.

The latter is  a bundle of nerve roots which resemble, and as such are often referred to as, the “horse’s tail.” In adults, the dura and arachnoid maters terminate at the second sacral vertebra (S2), and the pia mater forms a long thread-like structure called the filum terminale which starts at the conus medullaris and ends at the first coccygeal vertebra.

Myelination

Myelination of the spinal cord begins in the late fetal period and continues during the first postnatal year. The motor roots become myelinated before the sensory roots. In the spinal cord, myelin sheaths are formed by oligodendrocytes. This is unlike the peripheral nerves, whose myelin sheaths are formed by the plasma membranes of neural crest-derived Schwann (a.k.a. neurolemma) cells. These cells wrap themselves around the axons of somatic motor neurons, presynaptic and postsynaptic autonomic motor neurons, and somatic and visceral sensory neurons.

Once myelination of the spinal cord takes place, the tissue looks white on gross inspection. Because of this, these regions of myelinated axons are referred to as the white matter of the spinal cord.

Learn everything about the myelin and myelination process here.

Hindbrain

While the cervical flexure marks the transition from the hindbrain to the spinal cord, the pontine flexure separates the hindbrain into the rostral metencephalon, which becomes the pons and cerebellum. Inferiorly, the caudal myelencephalon becomes the medulla oblongata. The cavity in the hindbrain becomes the fourth ventricle, which is continuous with the central canal in the caudal medulla.

As the pontine flexure forms, the walls of the metencephalon shift laterally. The dorsal parts of the alar plates form the cerebellum. As the cerebellum grows, parts of it project into the fourth ventricle, eventually covering parts of the pons and medulla. Some neuroblasts from the alar plates become the cerebellar cortex, whereas others develop into the dentate, fastigial, globose, and emboliform cerebellar nuclei. Others develop into the pontine nuclei, cochlear and vestibular nuclei, and the sensory nuclei of the trigeminal nerve. Also passing through the pons are nerve fibers connecting the cerebrum, cerebellum, and spinal cord.

The medially situated gracile and laterally situated cuneate nuclei form when neuroblasts from the alar plate migrate into the the marginal zone of the myelencephalon. These nuclei receive the gracile and cuneate tracts, which extend from the dorsal spinal cord into the medulla. In the ventral medulla, bundles of fibers called pyramids contain the corticospinal tracts as they descend from the cerebral cortex into the spinal cord.

As the pontine flexure forms, the structure of the medulla changes: the alar plates move laterally towards the basal plates. This shift leads the sensory nuclei to develop laterally to the motor nuclei. Within the motor nuclei, neuroblasts organize into three columns. The general somatic efferents, which contain motor neurons of the hypoglossal nerve, lie medially. These are followed laterally by the special visceral efferents, which contain motor neurons supplying muscles derived from the pharyngeal arches. The general visceral efferents, which contain motor neurons of the vagus and glossopharyngeal nerves, are found at the most lateral edge of the nuclei.

With the exception of some neuroblasts that form the olivary nuclei more ventrally, neurons from the alar plates in the medulla arrange themselves in a similar manner. The general visceral afferents, receiving input from the viscera, lie medially; followed by the special visceral afferents, receiving taste fibers, and then the general somatic afferents, receiving sensory information from the surface of the face and head; and finally ending with the special somatic afferents, receiving auditory input, on the most lateral edge.

Choroid plexus and cerebrospinal fluid

The pia mater covers the ependymal roof of the fourth ventricle, and with the ependymal cells forms the tela choroidea. As the pia mater proliferates, the tela choroidea extends into the fourth ventricle, forming the choroid plexus. Similar choroid plexuses are also found in the roof the third ventricle and the medial walls of the lateral ventricles. Ependymal cells in these plexuses are responsible for producing CSF. Three foramina, the two lateral foramina of Luschka and the medial foramen of Magendie, form in the fourth ventricle, allowing CSF to flow from the ventricles into the subarachnoid spaces.

Midbrain

In the mesencephalon, the primordial midbrain, the ventricular system narrows. This narrowing produces the cerebral aqueduct of Sylvius, a pathway which connects and allows CSF to flow between the third and fourth ventricles. Neuroblasts from the mesencephalon region of the alar plate migrate into the tectum (roof) where they form four structures: two superior colliculi, associated with visual reflexes; and two inferior colliculi, associated with auditory reflexes. Neuroblasts from the basal plates form the red nuclei, oculomotor nuclei, trochlear nuclei, and reticular nuclei of midbrain.

The midbrain also contains a region of gray matter called the substantia nigra, which is responsible for producing dopamine. Whether it originates from the basal plate or the alar plate is still debated. The cerebral peduncles, which lie directly adjacent to the substantia nigra, are comprised of corticopontine, corticobulbar, and corticospinal tract fibers descending from the cerebral cortex down to the brainstem and spinal cord.

Forebrain

As the rostral neuropore closes, the optic vesicles develop as two outgrowths on either side of the forebrain. These eventually become the retina and optic nerve. More dorsally and rostrally, a second pair of diverticula called the telencephalic vesicles arise. These and the cavities within them become the cerebral hemispheres and lateral ventricles. The third ventricle forms from the cavities within the telencephalon and diencephalon, and is connected to each of the lateral ventricles via the ventricular foramina of Monro.

The diencephalon develops from the posterior part of the forebrain. Swellings in the lateral walls of the third ventricle form the thalamus, hypothalamus with mammillary bodies, and epithalamus.

The pineal gland develops in the midline from the caudal part of the roof of the diencephalon. The pituitary gland, which is located more rostrally, develops from two different sources. The anterior part of the pituitary comes from an upgrowth of oral ectoderm called the hypophysial diverticulum, or Rathke’s pouch. Rathke’s pouch eventually forms the adenohypophysis, the glandular component of the pituitary. The posterior part comes from a downgrowth of neuroectoderm from the diencephalon. It forms the neurohypophysial diverticulum, which becomes the neurohypophysis, the nervous component of the pituitary.

Growth of the hypophysial diverticulum begins during the third week of gestation. By the fifth week, the elongated diverticulum is constricted at its attachment to the oral epithelium, and is in contact superiorly with the infundibulum. The infundibulum is a derivative, along with the median eminence and pars nervosa, of the neurohypophysial diverticulum. The stalk attaching the hypophysial diverticulum to the oral cavity soon disappears, and the components of the adenohypophysis are formed: the pars anterior, pars intermedia, and pars tuberalis..

In the sixth week of development, the corpus striatum begins to form in the floor of each cerebral hemisphere, which can be identified by the seventh week. As the hemispheres expand, they cover the diencephalon, midbrain, and hindbrain, and eventually meet in the midline and flatten along their medial surface. The cortical walls of each hemisphere grows much faster than their floors, and as a result the hemispheres and the lateral ventricles within them become C-shaped. As the hemispheres grow, the caudal ends containing parts of the lateral ventricles turn ventrally and then rostrally, forming the temporal lobes and temporal ventricular horns. The cortices also grow over the external surface of the corpus striatum, burying what becomes the insular lobe at the base of the lateral sulcus, the Sylvian fissure.

Nerve fibers traveling to and from the cerebral cortex pass through the internal capsule, a pathway that divides the corpus striatum into the caudate and lentiform nuclei. The internal capsule is one of the first structures of a pathway that connects the cerebral cortex to the spinal cord. It is not, however, the only axonal pathway in the brain: white matter pathways are also necessary to connect different areas of the cerebral cortex with one another. This is accomplished with groups of fibers called commissures, which allow different parts of the brain to “communicate.” One of these is the optic chiasm, which develops from the ventral part of the lamina terminalis and contains fibers from the medial retinas that cross over to join the optic tracts on the opposite sides from whence they originate.

Another is the anterior commissure, which connects the olfactory bulb to related cortical regions, and connects those brain regions to each other. As its name suggests, the hippocampal commissure connects the hippocampal formations. By birth, the largest cerebral commissure, the corpus callosum, covers the roof of the diencephalon and provides a bridge of communication between the left and right cortices.

As the cerebral hemispheres continue to grow, they invaginate and fold, forming grooves called sulci and convolutions called gyri. This allows the cortical surface area to increase without the need to further expand the skull.