GRANULE CELL-DEVELOPMENT IN THE CEREBELLUM IS PUNCTUATED BY CHANGES IN SOX GENE-EXPRESSION

Development of the vertebrate cerebellum is unusual compared to most o ther regions of the brain since it involves two germinal regions. Most cell types arise from the luminal, ventricular zone as in other brain regions, but granule cells arise from the second germinal layer, the external granular layer (EGL). Our analysis of the temporal and positi onal expression of three members of the Sox gene family of transcripti on factors in the cerebellum shows that granule cell development is un usual compared to most other neurons of the central nervous system (CN S). We show that granule cell precursors lose expression of cSox2 and cSox3 as they migrate to form the EGL. The EGL is the first example of a germinal layer in the CNS which does not exhibit expression of thes e genes. Throughout most of the CNS cSox11 expression is very low in t he ventricular zone but increases dramatically as cells cease prolifer ation and migrate to form the subventricular zone. We also find that c Sox11 expression increases when cells of the cerebellum migrate to for m the EGL, but levels of expression as high as that in the subventricu lar zone are only seen when cells cease proliferation and migrate inwa rds to form the deep EGL, These observations demonstrate that cells of the proliferative superficial EGL differ qualitatively from cells of the ventricular zone in their expression of Sox genes whereas the post -proliferative cells of the deep EGL appear analogous, in their expres sion of Sox genes, to cells of the subventricular zone. (C) 1998 Elsev ier Science B.V.