Development of the neural tissue

In the early stages of development, three iconic layers of tissue develop within the embryo: the
endoderm, mesoderm, and ectoderm.

The nervous system develops from a section of the ectoderm called the neural plate, which
begins to differentiate under the influence of the nearby notochord and paraxial mesoderm
around the third week. The edges of the neural plate then elevate to form the neural folds. In a
process called neurulation, the neural folds curve upward and fuse to form the neural tube, which
will eventually become the CNS. The neural plate also forms the neural crest, cells of which will
later migrate to different parts of the body and become most of the cells in the PNS and ANS.

Neurulation begins in the fourth week of development (around the 22-23 day). The neural folds
fuse first in the cervical region and continue to fuse in both cranial (head) and caudal (tail)
directions until only the very ends of the tube remain open and connected with the amniotic
cavity. These openings are called neuropores, with the opening at the cranial end of the embryo
being the rostral neuropore, and the opening at the caudal end being the caudal neuropore. The
rostral neuropore closes around day 25, and the caudal neuropore closes approximately two days
after.

The neural tube becomes vascularized around the time that the neuropores close. Regions of the
neural tube begin to thicken, forming the brain and spinal cord, and the opening within the tube
begins to form the ventricles and central spinal canal.

During this time in development, certain genes become vital in ensuring accurate structural
layout of the CNS: Sonic hedgehog (Shh), the Pax genes, bone morphogenic proteins, and a
transforming growth factor (TGF-B) called dorsalin. These components are all influential in the
appropriate dorsoventral patterning of the developing neural tube.

Spinal cord development

The caudal part of the neural tube (i.e. the neural tube after the fourth pair of somites) becomes
the spinal cord. As the walls of the neural tube thicken, the neural canal becomes smaller and
smaller, until only a very thin central canal remains. The neuroepithelium surrounding this canal
transitions from pseudostratified columnar ependymal epithelium (the cell layer surrounding the
ventricles, constituting the ventricular zone) to instead form neurons and macroglia (including
astrocytes and oligodendrocytes) within the spinal cord.

The formation of neurons from neuroepithelial cells occurs when neuroepithelial cells in the
ventricular zone differentiate into primordial neurons called neuroblasts. These neuroblasts form
an intermediate zone called the mantle layer in between the ventricular and marginal zones. It is
in this layer that neurons will eventually form the gray matter of the spinal cord.

The primordial supporting cells of the CNS are called glioblasts or spongioblasts. As previously
noted, these cells also differentiate from neuroepithelial cells in the ventricular zone, but they do
so after the neuroblasts have already formed. After their formation, glioblasts migrate into the
intermediate and marginal zones, where they become astroblasts and oligodendroblasts.
Eventually, astroblasts will form astrocytes and oligodendroblasts will form oligodendrocytes.
When neuroblasts and glioblasts are no longer being produced, the remaining cells
become ependymal cells. These cells will line the central canal of the spinal cord as the
ependyma. The marginal zone becomes the white matter of the spinal cord as axons develop and
project into it from neuronal cell bodies of the brain, ganglia, and spinal cord.

In the late fetal period, once the CNS becomes fully vascularized, small cells
called microglia migrate into the CNS and can be found scattered throughout both the gray and
white matter. These derivatives of mesenchymal cells are mononuclear phagocytes that develop
in the bone marrow.

Microglial cells
As the neuroepithelial cells multiply and differentiate, they form thick walls, a thin roof, and
floor plates within the spinal cord. This results in the formation of the sulcus limitans, a long,
thin groove on each side of the spinal cord that separates the alar plates/lamina (the dorsal plates)
from the basal plates/lamina (the ventral plates). These plates span the entire length of the spinal
cord. The cell bodies in the alar plates develop into the dorsal gray columns (the dorsal gray
horns on cross-section), which contain afferent nuclei that form the dorsal roots of the spinal
nerves. As the alar plates continue to grow, the dorsal median septum is formed.
The ventral and lateral gray columns are formed from cell bodies in the basal plates (the ventral
and lateral gray horns respectively on cross-section). The ventral roots of the spinal nerves form
from the axons of cell bodies in the ventral horn as they project out of the spinal cord. Like the
dorsal median septum, the ventral median septum forms with the enlargement of the basal plates,
and eventually a deep longitudinal groove called the ventral median fissure will develop.

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.