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).
|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.
|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.