Development Of The Nervous System
The first signs of nervous system development occur in the third week of
gestation, under the influence of secreted factors from the notochord,
with the formation of a neural plate along the dorsal aspect of the
embryo. This plate broadens, folds (forming the neural groove) and fuses
to form the neural tube, which ultimately gives rise to the brain at its
rostral (i.e. towards the head) end and the spinal cord caudally (i.e. towards the
feet/tail end). The fusion begins approximately halfway along the neural groove
at the level of the fourth somite and continues caudally and rostrally with the
closure of the posterior/caudal and anterior/rostral neuropore during the
fourth week of gestation.
The development of the spinal cord
The process of neural tube fusion isolates a group of cells termed the neural
crest.
•
The neural crest gives rise to a range of cells
including the dorsal root ganglia (DRG) and peripheral components of the
autonomic nervous system (ANS; see Chapter 3).
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The DRG contain the sensory cell bodies which
send their devel- oping axons into the evolving spinal cord and skin.
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These growing neuronal processes or neurites
have an advancing growth cone that finds its appropriate target in the
periphery and central nervous system (CNS), using a number of cues including
cell adhesion molecules and diffusible neurotrophic factors (see Chapter 48).
The neural tube surrounds the neural canal, which forms the central canal
of the fully developed spinal cord.
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The tube itself contains the neuroblasts (ependymal
layer), which divide and migrate out to the mantle layer, where they
differentiate into neurones to form the grey matter of the spinal cord (see
Chapter 2).
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The developing processes from the
neuroblasts/neurones grow out into the marginal layer, which therefore
ultimately forms the white matter of the spinal cord.
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The dividing neuroblasts segregate into two
discrete populations, the alar and basal plates, which in turn
will create the dorsal and ventral horns of the spinal cord while a small
lateral horn of visceral efferent neurones (part of the ANS) develops at their
interface in the thoracic and upper lumbar cord (see Chapter 3).
•
This dorsoventral patterning relies, at least in
part, on factors secreted dorsally (bone morphogenic proteins (BMPs)) or ven-
trally from the notochord (sonic hedgehog (SHH)).
The
development of the brain
Adult
neurogenesis
Until recently it was believed that no new neurones could be born in the
adult mammalian brain. However, it is now clear that neural progenitor cells
can be found
in the adult
CNS, including in humans. These cells are predominantly
found in the dentate gyrus of the hippocampus (see Chapter 45) and just next to
the lateral ventricles in the subventricular zone (SVZ). They may also exist at
other sites of the adult CNS but this is contentious. They respond to a number
of signals and appear to give rise to functional neurones in the hippocampus
and olfactory bulb, with the latter cells migrating from the SVZ to the
olfactory bulb via the rostral migratory stream (RMS). They may therefore
fulfil a role in certain forms of
memory and possibly in mediating the therapeutic effects of some drugs such as
antidepressants (see Chapter 57).
Disorders of
central nervous system embryogenesis
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Anencephaly occurs when there is
failure of fusion of the anterior rostral neuropore. The cerebral vesicles fail
to develop and thus there is no brain formation. The vast majority of fetuses
with this abnormality are spontaneously aborted.
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Spina bifida refers to any defect
at the lower end of the vertebral column and/or spinal cord. The most common
form of spina bifida refers to a failure of fusion of the dorsal parts of the
lower vertebrae (spina bifida occulta). This can be associated
with defects in the meninges and neural tissue which may herniate through the
defect to form a meningocoele and meningomyelocoele,
respectively. The most serious form of spina bifida is when nervous tissue is
directly exposed as a result of a failure in the proper fusion of the
posterior/caudal neuropore. Spina bifida is often associated with hydrocephalus
(see Chapter 5). Occasionally, bony defects are found at the base of the skull
with the formation of a meningocoele. However, unlike the
situation at the lower spinal cord, these can often be repaired without any
neurological deficit being accrued.
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Cortical dysplasia refers to a
spectrum of defects that are the result of the abnormal migration of developing
cortical neurones. These defects are becoming increasingly recognized with
improved imaging of the human CNS, and are now known to be an important cause
of epilepsy (see Chapter 61).
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Many intrauterine infections (such as rubella),
as well as some environmental agents (e.g. radiation), cause major problems in
the development of the nervous system. In addition, a large number of rare
genetic conditions are associated with defects of CNS development, but these
lie beyond the scope of this book.
