A Role for p27/Kip1 in the Control of Cerebellar Granule Cell Precursor Proliferation

摘要: During development, control of proliferation neuronal precursor cells plays a crucial role in determining the number neurons. Proliferation is driven by mitogens, but how it terminated remains mystery. In this study, we examined cyclin-dependent kinase inhibitors cerebellar granule cell precursors (GCPs). Among examined, only p27/Kip1 (p27) was expressed at significant levels lineage developing and adult cerebellum. cerebella, p27 external germinal layer (the deeper regions), molecular layer, layer. We isolated purified GCPs from cerebella mice their bromodeoxyuridine (BrdU) uptake expression various times. found that there an inverse correlation between BrdU expression. Even presence saturating amounts Sonic hedgehog, potent mitogen, eventually stopped dividing differentiated, expressing strongly. also which one or both copies gene have been inactivated targeted disruption were larger than those wild-type mice. cultures, prepared p27-deficient showed enhanced compared with Taken together, these results suggest intracellular mechanism stops GCP division causes to differentiate part mechanism.