IN THE PRECEDING CHAPTER, WE DESCRIBED how local inductive signals pattern the neural tube and establish the early regional subdivisions of the nervous system—the spinal cord, hindbrain, midbrain, and forebrain. Here, we turn to the issue of how progenitor cells within these regions differentiate into neurons and glial cells, the two major cell types of the nervous system. The mature brain comprises billions of nerve cells and a similar number of glial cells arranged in complex patterns, yet its precursor, the neural plate, initially contains only a few hundred cells arranged in a simple columnar epithelium. From this observation alone, it should be apparent that the generation of neural cells and their delivery to appropriate sites must be carefully regulated.
We begin by discussing some of the molecules that specify neuronal and glial cell fates. The basic mechanisms of neurogenesis endow cells with common neuronal properties, features that are largely independent of the region of the nervous system in which they are generated or the specific functions they perform. We also describe mechanisms by which developing neurons become specialized, for example by acquiring the machinery to synthesize specific neurotransmitters.
We next discuss how neurons are delivered from their sites of origin to their final destinations. A common theme is that neurons are frequently “born”—that is, become postmitotic—far from where they end up, for example, in the layers of the cerebral cortex or the ganglia of the peripheral nervous system. Such distances necessitate elaborate migratory mechanisms, which differ among neuronal types.
After the identity and functional properties of the neuron have begun to emerge, additional developmental processes determine whether the neuron will live or die. Remarkably, approximately half of the neurons generated in the mammalian nervous system are lost through programmed cell death. We examine the factors that regulate the survival of neurons and the possible benefits of widespread neuronal loss. Finally, we describe a core biochemical pathway in nerve cells destined for elimination.
The Proliferation of Neural Progenitor Cells Involves Symmetric and Asymmetric Cell Divisions
Histologists in the late 19th century showed that neural epithelial cells close to the ventricular lumen of the embryonic brain exhibit features of mitosis. We now know that the proliferative zones surrounding the ventricles are the major sites for the production of neural cells in the central nervous system. Moreover, newborn cells in the proliferative zones often become committed to neuronal or glial fates before migrating from these zones.
At early stages of embryonic development, most progenitor cells in the ventricular zone of the neural tube proliferate rapidly. Many of these early neural progenitors have the properties of stem cells: They can generate additional copies of themselves, a process called self-renewal, and also give rise to differentiated neurons and glial cells. In a later chapter, we will describe the more recent discovery that stem ...