The central nervous system (CNS) has many neuronal cell types, and within a given brain region, these different types of neurons are present in precise ratios. Such regular ratios of neurons are characteristic of all brain regions and are fundamental to the proper functioning of the nervous system. However, virtually nothing is known of the mechanisms that regulate the production of the various types of neurons during the development of the CNS. Several lines of evidence indicate that this process is in some way controlled by the microenvironment of the developing CNS. The experiments outlined in this proposal will test several specific predictions of a model of central neurogenesis in which age-dependent changes in the retinal microenvironment determine the types of neurons that are produced at any given time. The experiments can be divided into two parts: 1. What factors regulate the proliferation of the germinal neuroepithelial cells during retinal histogenesis? 2. What are the cellular and molecular mechanisms involved in the generation of particular types of neurons/glia from the multipotent progenitor? An understanding of the factors that regulate CNS neuronal proliferation will undoubtedly prove invaluable in future attempts at reconstruction and regeneration of the damaged CNS as well as providing insight into the mechanisms of teratological agents that disrupt the normal development of the nervous system and neoplastic transformation of germinal neuroepithelial cells.
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