Regulation of Neuronal Proliferation and Differentiation

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DESCRIPTION (provided by applicant): The overall long term objective of these studies is to provide a better understanding of how different types of retinal neurons are generated during retinal development. Over ten years ago, we began studies to determine how the diversity of retinal cell types comes about during the process of histogenesis. We used retina as a model system to develop principles for the generation of neuronal diversity that could apply to the central nervous system in general. Over the past ten years, our studies and those of other have shown that individual cell fates arise from an interplay between the cellular microenvironment and the intrinsic transcriptional regulators expressed in a cell. While we have derived this principle from studies of various retinal cell types, it is nowhere better demonstrated than in the development of the cone photoreceptors, and in this application we have decided to focus our efforts to the understanding of how diversity is generated within this specific cell class. Although these studies address a fundamental feature of developmental neurobiology, since they will result in a better characterization of gene expression in cone photoreceptors, they will also provide information that may prove useful for the treatment of degenerative retinal disorders, such as macular degeneration. In addition to potentially identifying new genes important for cone photoreceptor biology, a better understanding of the factors that direct retinal cells to specific fates will also be critical in developing rational therapies for repair of the retina using retinal stem cells.