During the development of the vertebrate central nervous system, neurons are generated from populations of stem cells that reside within the neuroepithelium of the neural tube in a process termed neurogenesis. Neural stem cells are not only essential for the production of neurons during embryonic development, they also have therapeutic potential as a source of neurons to treat neurodegenerative diseases. The formation of neuronal stem cells and their differentiation into neurons is largely controlled by a family of basic-helix-loop-helix (bHLH) transcription factors, including the neurogenins. The neurogenins, for example, will promote the formation of ectopic neural stem cells and their differentiation when ectopically expressed in developing neural tissue. The experiments proposed in the application are designed to determine how the neurogenins promote neurogenesis, using the primary nervous system in Xenopus embryos as a model system. Using primary neurogenesis as an assay, the factors that regulate the expression and activity of the neurogenins will be identified and studied. In addition, genes that are activated by the neurogenins will be isolated and their function in establishing neural stem cells and their differentiation into neurons will be determined. These experiments will provide new information about how neural stem cells form in embyros, and how the differentiation of these cells is controlled to generate the neurons that make up the vertebrate central nervous system.
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