Downregulation of Rho-GDI gamma promotes differentiation of neural stem cells.

Rho-GDIgamma belongs to the Rho-GDI protein family, which was observed to have high level expression in the entire brain. Although it exists in neuronal population, its physiological function is poorly understood. This study shows that Rho-GDIgamma is a key factor in the G13 signaling pathway based on an analysis of global gene expression. By using RNAi technology to downregulate expression of Rho-GDIgamma we found distinct morphological changes in neural stem cell line C17.2. More important, RT-PCR confirmed that RNAi-mediated downregulation of Rho-GDIgamma decreased expression of Rho-GDIgamma-regulated genes RhoA, Cdc42, Limk2, and N-WASP and slightly increased expression of Rac1. Further, immunochemical staining indicated that downregulation of Rho-GDIgamma increased the tendency of C17.2 cells to differentiate. These data strongly suggest that Rho-GDIgamma plays a key role in the differentiation of neural stem cells.