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 ? ?
| Emmenegger, B A; Hwang, E I; Moore, C et al. (2013) Distinct roles for fibroblast growth factor signaling in cerebellar development and medulloblastoma. Oncogene 32:4181-8 |
| Emmenegger, Brian A; Wechsler-Reya, Robert J (2008) Stem cells and the origin and propagation of brain tumors. J Child Neurol 23:1172-8 |
| Fogarty, Marie P; Emmenegger, Brian A; Grasfeder, Linda L et al. (2007) Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells. Proc Natl Acad Sci U S A 104:2973-8 |
| Read, Tracy-Ann; Hegedus, Balazs; Wechsler-Reya, Robert et al. (2006) The neurobiology of neurooncology. Ann Neurol 60:3-11 |
| Lee, Audra; Kessler, Jessica D; Read, Tracy-Ann et al. (2005) Isolation of neural stem cells from the postnatal cerebellum. Nat Neurosci 8:723-9 |
