alpha6 integrin subunit regulates cerebellar development
Résumé
Mutations in genes encoding several basal lamina components as well as their cellular receptors disrupt normal deposition and remodeling of the cortical basement membrane resulting in a disorganized cerebral and cerebellar cortex. The alpha6 integrin was the first alpha subunit associated with cortical lamination defects and formation of neural ectopias. In order to understand the precise role of alpha6 integrin in the central nervous system (CNS), we have generated mutant mice carrying specific deletion of alpha6 integrin in neuronal and glia precursors by crossing alpha6 conditional knockout mice with Nestin-Cre line. Cerebral cortex development occurred properly in the resulting alpha6 (fl/fl;nestin-Cre) mutant animals. Interestingly, however, cerebellum displayed foliation pattern defects although granule cell (GC) proliferation and migration were not affected. Intriguingly, analysis of Bergmann glial (BG) scaffold revealed abnormalities in fibers morphology associated with reduced processes outgrowth and altered actin cytoskeleton. Overall, these data show that alpha6 integrin receptors are required in BG cells to provide a proper fissure formation during cerebellum morphogenesis.