Development of the spinal cord

The nervous system develops from an area of embryonic ectoderm called the neural plate which appears during week 3. The underlying notochord and adjacent mesoderm induce the formation of the neural plate. The neural tube and the neural crest differentiate from the neural plate.

The neural tube gives rise to the central nervous system (brain and spinal cord; . The neural crest gives rise to the peripheral nervous system (cranial, peripheral, autonomic ganglia and nerves) and Schwann cells, pigment cells, odontoblasts, meninges, and bones and muscles of the head .  

Central nervous system Formation of the neural tube begins during the early part of week 4 (22-23 days) in the region of the 4th to 6th pairs of somites (future cervical region of the spinal cord; At this stage ,the cranial 2/3 of the neural plate and neural tube down to somites #4 represent the brain and the caudal 1/3 of the neural tube and plate represent the spinal cord.

Neural folds fuse and the neural tube is temporarily open at both ends, communicating freely with the amniotic cavity. The rostral neuropore closes around day 25 and caudal neuropore on day 27. Walls of the neural tube thicken to form the brain and spinal cord. The lumen of the neural tube is converted to the ventricular system of the brain and the central canal of the spinal cord.

The spinal cord is formed from the neural tube caudal to somites 4. The central canal is formed by week 9 or 10 . Pseudostratified, columnar neuroepithelium in the walls constitute the ventricular zone (ependymal layer) and give rise to all neurons and macroglial cells (astroglia and oligodendroglia) in the spinal cord. The outer parts of the neuroepithelial cells differentiate into a marginal zone which will give rise to the white matter of the spinal cord as axons grow into it from neurons in the spinal cord, spinal ganglia and brain. Neuroepithelial cells in the ventricular zone differentiate into neuroblasts and form an intermediate zone between the ventricular and marginal zones. They will give rise to neurons.

Glioblasts (spongioblasts) differentiate from neuroepithelial cells after neuroblast formation has stopped. They migrate from the ventricular zone into the intermediate and marginal zones. Some become astroblasts and then astroglia (astrocytes). Others become oligodendroblasts and then oligodendroglia (oligodendrocytes). The remaining neuroepithelial cells differentiate into ependymal cells lining the central canal of the spinal cord Microglia are derived from the mesenchymal cells. They invade the nervous system late in the fetal period after penetration from blood vessels.

Proliferation and differentiation of the neuroepithelial cells in the developing spinal cord produce thick walls and thin roof and floor plates. A shallow longitudinal sulcus limitans appears in the lateral walls of the spinal cord and separates the dorsal alar plate from the ventral basal plate

Alar plates: cells form the dorsal horns and will have afferent functions. Basal plates: cells form the ventral and lateral horns and will have efferent functions. Axons grow out of the spinal cord to form the ventral roots. The dorsal root ganglia are formed from the neural crest cells. Their axons enter the spinal cord and form the dorsal roots.

Mesenchyme surrounding the neural tube condenses to form the primitive meninx. The outer layer thickens to form the dura mater. The inner layer remains thin and forms the pia-arachnoid

Positional changes of the developing spinal cord In the embryo, the spinal cord extends the entire length of the vertebral canal and the spinal nerves pass through the intervertebral foramina near their levels of origin. This relationship does not persist because the spine and the dura mater grow more rapidly than the spinal cord. The caudal end of the spinal cord comes to lie at relatively higher levels.

Positional changes of the developing spinal cord. At month 6 of gestation, the end of the spinal cord lies at the level of S1. In the newborn infant, it lies at L 3 In the adult, it lies at L 1. Lumbar and sacral spinal nerve roots run obliquely from the spinal cord to their corresponding intervertebral foramina inferiorly.

Congenital malformations: are mostly due to the defective closure of the caudal neuropore at the end of week 4. The defects will involve the tissue overlying the spinal cord (meninges, vertebral arch, dorsal muscles and skin). involving the spinal cord and vertebral arches are called spina bifida (nonfusion of the vertebral arches

Spina bifida occulta. is a defect in the vertebral arch (neural arch) resulting from failure of the halves of the vertebral arch to grow normally and fuse in the median plane. occurs at L 5 or S 1 vertebra in about 10% of the population. may only be evident as a small dimple with a tuft of hair. produces no clinical symptoms although a small percentage may have significant defects of the underlying spinal cord and spinal roots.

The dimple may be connected by a fibrous cord with the dura mater. Spinal dermal sinus representing the area of closure of the caudal neuropore at the end of week 4, may exist. It is the last place of separation between the ectoderm and the neural tube. The dimple may be connected by a fibrous cord with the dura mater.

Intramedullary dermoids are tumors arising from surface ectodermal cells incorporated into the neural tube during closure of the caudal neuropore.

Spina bifida cystica is a protrusion of the spinal cord and/or meninges through the defective neural arch. is present in 1/1000 births. may result in loss of sensation in corresponding dermatome, complete or partial skeletal muscle paralysis, sphincter paralysis (with lumbar meningomyeloceles) and saddle anesthesia.

Spina bifida with meningocele: only meninges and cerebrospinal fluid in the sac. with meningomyelocele : spinal cord and nerve roots included with meninges and CSF in the sac, covered by skin or thin membrane. There are marked neurological deficits inferior to the sac, due to incorporation of the neural tissue into the wall of the sac. with myeloschisis (with myelocele: open spinal cord due to failure of neural folds to fuse. The spinal cord in this area is a flattened mass.

cystica and/or meroanencephaly (absence of part of the brain; is suspected in utero when there is a high-level of alpha-fetoprotein in the amniotic fluid or in the maternal blood serum. Amniocentesis or ultrasound should be performed at about week 10 when the vertebral column becomes visible.

The telencephalon is the most rostral of the secondary vesicles. Two buds emerge from either side of its rostral portion to form the two telencephalic vesicles. These two vesicles grow rapidly to form the two cerebral hemispheres. First they grow back over the diencephalon, then they grow down to cover its sides.

Another pair of vesicles will also sprout from the ventral surface of these cerebral hemispheres to become the olfactory bulbs and other structures that contribute to the sense of smell. Various structures will then emerge from the walls of the telencephalon while the white matter that connects these structures develops as well. The neurons of the telencephalon wall proliferate to form three distinct regions—the cerebral cortex, the basal telencephalon, and the olfactory bulb.

The axons of these neurons will also gradually elongate to make connections with the other parts of the nervous system. Some of these axons will constitute the cortical white matter that arises from and projects to neurons in the cortex. Others will form the corpus callosum, the band of nerve fibres that connects the two hemispheres of the brain. Still others—those of the internal capsule—will connect the cortical white matter to the brain stem, generally by way of the thalamus. For example, the axons arising from the motor cortex will pass through the internal capsule to connect to the motor neurons in the spinal cord.

In the the remaining space between the telencephalon and the diencephalon on either side, the two cerebral ventricles (also known as the lateral ventricles or the first and second ventricle) form, while the third ventricle forms in the space at the centre of the diencephalon. The diencephalon also differentiates into distinct areas: the thalamus and the hypothalamus.  

On either side of the diencephalon, two secondary vesicles also develop—the optic vesicles. The optic vesicles lengthen and fold inward to form the optic peduncles and optic cups, which will give rise to the retinas and the optic nerves. The retinas and the optic nerves are therefore not part of the peripheral nervous system, but rather they are integral parts of the brain!

Compared with the prosencephalon (telencephalon and diencephalon), the mesencephalon undergoes far less transformation. Its dorsal surface forms the tectum, while its floor forms the tegmentum. While these structures are differentiating, the cavity that separates them shrinks to a narrow channel called the cerebral aqueduct. The rostral portion of this aqueduct opens into the third ventricle of the diencephalon.

The mesencephalon serves as the passageway for the bundles of fibres that connect the cortex to the spinal cord—both those that arise from the sensory system and those that descend to participate in movement control. The tectum differentiates into two structures. One, the superior colliculus, receives information directly from the eye and controls eye movements. The other, the inferior colliculus, receives information from the ear and serves as an important relay in the auditory pathways.

The tegmentum is one of the most colourful areas of the brain. It contains the substantia nigra (“black matter”) and the red nucleus, two structures that are involved in controlling voluntary movement. Other groups of cells in the mesencephalon project their axons diffusely into large areas of the brain and influence a wide variety of functions, such as consciousness, mood, pleasure and pain.

Caudal to the mesencephalon lies the metencephalon, which is the rostral portion of the hindbrain and differentiates into two major structures: the cerebellum and the pons. The cerebellum arises from the thickening of the tissue covering the lateral walls of the neural tube at this location. The two masses thus formed ultimately fuse dorsally to form the cerebellum. During this time, a swelling develops on the ventral side of the metencephalon and forms the pons. This structure is an important information pathway between the brain, the cerebellum, and the spinal cord.

In the the myelencephalon (the caudal portion of the hindbrain) the changes are less spectacular. The ventral and lateral regions of this structure swell to form the medulla oblongata. Along the ventral aspect of the medulla, the two medullary pyramids will also develop, formed by the passage of the corticospinal bundles responsible for voluntary movement. Lastly, the central canal, which persists while the medulla is forming, becomes the fourth ventricle

The entire portion of the neural tube that lies caudal to the five secondary vesicles becomes the spinal cord through a fairly direct process of differentiation consisting in the thickening of the tube walls. This thickening gradually reduces the diameter of the neural tube until it becomes the very narrow spinal canal.

As the cross-section shown here illustrates, the cell bodies of the neurons in the spinal cord are concentrated in the grey matter at the centre (the butterfly-shaped area), while the white matter at the periphery is composed of bundles of axons. The grey matter of the spinal cord is in turn divided into the dorsal horn, which receives sensory inputs, and the ventral horn, whose neurons innervate the skeletal muscles.

Likewise, within the white matter, there develop dorsal columns composed of sensory axons that ascend to the brain and lateral columns composed of corticospinal axons that descend to transmit signals for controlling movement. Between the dorsal and ventral horns, a large number of interneurons also develop that are involved in various types of reflexes as well as in establishing networks that perform initial processing of the information received in the spinal cord.