MORPHOGENESIS OF
THE BRAIN, SPINAL CORD, AND PERIPHERAL NERVOUS SYSTEM: THE EMBRYO FROM 28 THROUGH 36 DAYS
Within an additional 4 days of embryogenesis, the neural tube closes completely, and the developing nervous system undergoes additional changes that define the stem cell populations that generate all of the distinct structures of the mature brain and peripheral nervous system. These changes are seen anatomically as the emergences of a series of bulges, bends, and grooves that distinguish specific regions of the developing nervous system from the anterior to posterior end. At the anterior end of the closed neural tube, the neuroepithelium expands into a hollow globe called the prosencephalon. The neural stem of the prosencephalon is specified to generate all of the neurons that will comprise the major regions of the forebrain. Subsequently, two bilaterally symmetric structures emerge from the lateral/anterior aspect of the prosencephalon. These are the optic vesicles that will generate all of the neural cells of the retina. Immediately posterior to the prosencephalon, the neural tube bends at a point referred to as the cephalic flexure. This bending point begins the process by which the brain (and the head) will become distinct from the spinal cord and rest of the body. The stem cells in the neural tube in the region of the cephalic flexure become specified to give rise to the structures of the midbrain (also referred to as the mesencephalon).
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| CENTRAL NERVOUS SYSTEM AT 28 DAYS |
The region of the neural tube
posterior to the mid-brain undergoes a dramatic series of morphogenetic changes
that transform it into the rhombencephalon. The most noticeable event is
the establishment of a series of repeated bulges and grooves along the
anterior/posterior axis that constitute a series of transient domains referred
to collectively as rhombomeres. The neural stem cells in each rhombomere
acquire distinct patterns of gene expression based upon their location. These
distinctions then facilitate local genesis of motor neurons that give rise to
the cranial motor nerves, and to sensory neurons
that provide the targets for peripheral cranial sensory inputs to the brainstem
(including the cerebellum/pons, also known as the metencephalon, and
the medulla oblongata, also known as the myelencephalon). The
relationship between rhombomeres and the developing structures of the head is
quite precise. Indeed, the neural crest that emerges from the neural tube in
the region of each rhombomere (note that there is no neural crest associated
with the prosencephalon) establishes cranial target
structures that are often innervated by motor neurons generated in the same
rhombomere. Similarly, cranial ganglia derived from neural crest that migrates
from distinct rhombomeres have a specific relationship with target nuclei
generated within the relevant rhombomere.
Within an additional 8 days of
development (36 days), the basic topography of the entire nervous system has
been established, as have most of the component regions
that will then grow and differentiate through- out the balance of
embryogenesis. The prosencephalon becomes further subdivided into two telencephalic
vesicles (collectively called the telencephalon) that will give rise
to the bilaterally symmetric structures of the forebrain: the cerebral cortical
hemispheres, the hippocampi, the basal ganglia, basal forebrain nuclei, and the
olfactory bulbs. The remainder of the prosencephalon, posterior to the
telencephalic vesicles, becomes the diencephalon, which will generate
the epithalamus (dorsal structures known as the habenula), thalamus (the relay
nuclei that project to the cerebral cortex), and hypothalamus (motor/endocrine
control nuclei that regulate visceral and reproductive function and
homeostasis). The mesencephalon, rhombencephalon, and myelencephalon become
further differentiated, and the cranial motor nerves (see darker blue in
the upper panel of Plate
1-4), sensory ganglia, and
associated cranial sensory nerves (lighter pink, Plate 1-4) become clearly visible along the anterior to
posterior extent of the midbrain and hind-brain. In parallel, the motor nerves
and sensory ganglia and associated sensory nerves of the rest of the body
become visible along the anterior to posterior extent of the spinal cord.
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| CENTRAL NERVOUS SYSTEM AT 36 DAYS |
While the neural tube is acquiring
additional regional identity that prefigures the final generation of the mature
neurons and glia in distinct brain regions, the space enclosed by the neural
tube becomes further defined as the ventricular system. The ventricular
system will be filled with a distinctive fluid—cerebrospinal fluid (CSF)—that
provides specific signaling molecules to neural stem cells during development
and then maintains the appropriate ionic balance for electrical signaling in
the more mature nervous system. Initially, at 28 days of embryonic development,
the ventricular spaces are referred to as the prosocele,
mesocele, and rhombocele, corresponding to the primitive regions of
the neural tube that surround them. Within 8 days, the ventricular system has
become more elaborate, in parallel with the elaboration of the forebrain,
midbrain, and hindbrain. There are now two lateral ventricles enclosed
by the telencephalic vesicles, a diocele that will become the third
ventricle, a mesocele that will become the cerebral aqueduct, and a metacele and myelocele that will collectively
grow into the fourth ventricle. The ventricular space enclosed by the
developing spinal cord is now defined as the central canal. Thus by
approximately 36 days—a bit more than 1 month into the 9-month period of
gestation—the fetus has acquired all of the major regions of the brain and the
anatomic divisions of the ventricular system.
