Neural stem or progenitor cells (NSC/NPCs) able to generate the different neuron and glial cell types of the cerebellum have been isolated in vitro, but their identity and location in the intact cerebellum are unclear. Here, we use inducible Cre recombination in GFAPCreERT2 (GCE) mice to irreversibly activate reporter gene expression at P2, P5 and P12 in cells with GFAP promoter activity and analyze the fate of genetically tagged cells in vivo. We show that cells tagged at P2-P5 with βgal or EGFP reporter genes generate at least 30% of basket and stellate GABAergic interneurons in the molecular layer (ML) and that they lose their neurogenic potential by P12, after which they generate only glia. Tagged cells in the cerebellar white matter (WM) were initially GFAP/S100β+ and expressed the NSC/NPCs proteins LeX, Musashi1 and Sox2 in vivo. One week after tagging, reporter+ cells in the WM up-regulated the neuronal progenitor markers Mash1, Pax2 and Gad-67. These Pax2+ progenitors migrated throughout the cerebellar cortex, populating the ML and leaving the WM by P18. These data suggest that a pool of GFAP/S100β+ glial cells located in the cerebellar WM generate a large fraction of cerebellar interneurons for the ML within the first postnatal 12 days of cerebellar development. This restricted critical period implies that powerful inhibitory factors may restrict their fate potential in vivo at later stages of development.
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