Growth arrest specific gene 1 is a positive growth regulator for the cerebellum

Postnatal cerebellum development involves the generation of granule cells a nd Bergmann glias (BGs). The granule cell precursors are located in the ext ernal germinal layer (EGL) and the BG precursors are located in the Purkinj e layer (PL). BGs extend their glial fibers into the EGL and facilitate gra nule cells' inward migration to their final location. Growth arrest specifi c gene 1 (Gas1) has been implicated in inhibiting cell-cycle progression in cell culture studies (G. Del Sal et al., 1992, Cell 70, 595-607). However, its growth regulatory function in the CNS has not been described. To inves tigate its role in cerebellar growth, we analyzed the Gas1 mutant mice. At birth, wild-type and mutant mice have cerebella of similar size; however, m ature mutant cerebella are less than half the size of wild-type cerebella. Molecular and cellular examinations indicate that Gas1 mutant cerebella hav e a reduced number of granule cells and BG fibers. We provide direct eviden ce that Gas1 is required for normal levels of proliferation in the EGL and the PL, but not for their differentiation. Furthermore, we show that Gas1 i s specifically and coordinately expressed in both the EGL and the BGs postn atally. These results support Gas1 as a common genetic component in coordin ating EGL cell and BG cell proliferation, a link which has not been previou sly appreciated. (C) 2001 Academic Press.