Fig. 8

A schematic for cerebellar hypoplasia caused by deletion of Ggpps. This model depicts molecular mechanisms by which Ggpps regulates cerebellar morphogenesis. Deletion of Ggpps in cerebellar NPCs prevents the geranylgeranylation of proteins and causes abnormal prenylation of RhoA. Post-translational modification of RhoA leads to translocation of RhoA in the cytosol. Accumulation of cytosolic RhoA may reduce the distribution of RhoA in the nucleus. The latter regulates p21 expression through a transcription-related mechanism. Increased p21 then inhibits the proliferation of NPCs, which results in depletion of NPCs and GCPs. Consequently, the differentiation of neurons and glial cells is severely impaired in the cerebellum, followed by cerebellar hypoplasia and ataxia