Control of Cerebellar Development by FGF signaling

Duke University, Durham NC

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The cerebellum plays a critical role in motor coordination and learning. Proper development of the cerebellum requires a delicate balance between proliferation of neuronal precursors and differentiation of these cells into neurons. The proliferation of the major cell type in the cerebellum, the granule cell, is regulated by the secreted molecule Sonic hedgehog (Shh). But the signals that cause granule cells to stop proliferating and differentiate are unknown. We have found that basic fibroblast growth factor (bFGF) is a potent inhibitor of Shh-induced proliferation, suggesting that it might be a key regulator of granule cell cycle exit and differentiation. The studies described here are aimed at determining the mechanisms of FGF effects on granule cell precursors and the importance of FGF signaling for normal granule cell development. These studies will not only lend insight into the molecular mechanisms that control granule cell differentiation, but will also have important implications for our understanding of Shh and FGF interactions in other parts of the nervous system. Moreover, by deepening our understanding of cell cycle regulation in normal granule cell precursors, these studies may shed light on the loss of cell cycle control in medulloblastoma, the most common malignant brain tumor in children [unreadable] [unreadable]