The developmental anatomy is seen at its simplest in the spinal cord. As it develops, the epithelium forming the walls of the posterior neural tube becomes enormously thickened as the cells proliferate and differentiate, creating a highly organized structure of neurons and glial cells, surrounding a small central channel. Bands of neurons with different future functions—and expressing different genes—are laid out along the dorsoventral axis of the tube. Motor neurons (those that control the muscles) are located ventrally, whereas neurons that process sensory information are found dorsally. This pattern is established by opposing gradients of morphogens. These are secreted by specialized groups of cells that run the length of the ventral and dorsal midlines of the neural tube (Figure 21–69). The two morphogen gradients—consisting of Sonic hedgehog protein from the ventral source and BMP and Wnt from the dorsal source—help induce different groups of proliferating neural progenitor cells and differentiating neurons to express different combinations of transcription regulators. These regulators in turn drive the production of different combinations of neurotransmitters, receptors, cell–cell adhesion proteins, and other molecules, creating terminally differentiated neurons that will form synaptic connections selectively with the right partners and exchange appropriate signals with them.
genesis of neurons outgrowth of axons and dendrites synapse formation
Figure 21–68 The four phases of neural development.
refnement of synaptic connections 1200 Chapter 21: Development of Multicellular Organisms lumen of groups ofneural tube differentiatingfoor plate and notochord (ventricle) neurons
Extracellular morphogen gradients, however, are not the only way to generate cell diversity. As we saw earlier in our discussion of Drosophila neuroblasts (see Figure 21–36), different cell types can also be generated by temporal patterning, in which an intracellular program changes the character of a progenitor cell over time, giving rise to different cell types as development progresses. This mechanism also seems to operate in vertebrate neurogenesis. The most striking illustration comes from study of another part of the CNS—the mammalian cerebral cortex.
Although the cerebral cortex is the most complex structure in the human body, it has a simple beginning—from the anterior neural tube. As in the spinal cord, the cells that form the walls of the tube proliferate, and the neuroepithelium thickens and expands as they divide. On a predictable schedule, the divisions of the neuroepithelial cells begin to produce a succession of cells committed to terminal differentiation as neurons. These future neurons are born close to the lumen (the central cavity) of the tube. From here, they migrate outward, losing attachment to the lumenal surface and crawling outward along neighboring cells that continue to span the full thickness of the neuroepithelium. These latter neuroepithelial cells do double duty, functioning as progenitors of neurons and glia, and as supporters of the epithelial architecture. They become stretched out as radial glial cells, forming a scaffold that continues to span the neuroepithelium even as this grows to an enormous thickness (Figure 21–70). At the same time, the radial glial cells continue to divide as neural precursors, giving rise to both neurons and glial cells—new radial glial cells as well as glial cells of other types. The newborn neurons, migrating along the radial glial cells, find their appropriate resting places in the developing cortex, where they mature, and from these sites they send out their axons and dendrites. The first-born neurons settle closest to their birthplace near the lumen, while neurons born later crawl past them to settle farther out (Figure 21–71). The successive generations of neurons thus build up as a series of cortical layers, ordered by birthdate and endowed with different intrinsic characters.