In early cortical development neural progenitor cells (NPCs) expand their population in Rabbit Polyclonal to RHG17. the ventricular zone (VZ) and produce neurons. proportion of Ki67-positive cells in NPCs. However knockdown of RhoG did not affect differentiation and survival of NPC. The RhoG-induced promotion of BrdU incorporation required phosphatidylinositol 3-kinase (PI3K) activity but not the conversation with ELMO. Taken together these results indicate that RhoG promotes NPC proliferation through PI3K in cortical development. INTRODUCTION In mammalian brain cerebral cortex is usually highly organized and its proper development is necessary for higher brain functions. Cortical neurons are generated in the ventricular zone (VZ) and sequentially migrate toward the pial side of cortex from the VZ to the cortical plate (CP) through the intermediate zone (IZ) to form six cell layers (Gupta genes participate N-Methyl Metribuzin in the NPC fate decision or proliferation. However the mechanisms of intracellular signal transduction in the regulation of NPC proliferation are still largely unknown. In this study we examined the role of RhoG in the developing cerebral cortex. RhoG is usually expressed in the VZ which is a highly proliferative region at early stages of cortical development. Overexpression of constitutively active RhoG promoted NPC proliferation whereas it was suppressed by RNAi-mediated knockdown of RhoG in vitro or in vivo. In addition BrdU incorporation into NPCs was enhanced by constitutively active RhoG and suppressed by knockdown of RhoG. However knockdown of RhoG affected neither the percentage of Nestin+ cells nor the number of apoptotic cells indicating that RhoG seems to regulate neither fate determination nor cell survival in NPCs. Taken together we conclude that RhoG is usually a key positive regulator for proliferative activity of NPCs. Previous studies using cell lines have provided some evidence that RhoG is usually involved in cell proliferation. N-Methyl Metribuzin In NIH3T3 cells expression of constitutively active RhoG increases cell saturation density and dominant unfavorable RhoG-expressing cells increase doubling time at first and then grow normally but stop growing at lower saturation density. Moreover constitutively active RhoG potentiates Ras-induced focus formation (Roux (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E09-03-0200) on October 7 2009 REFERENCES Blangy A. Vignal E. Schmidt S. Debant A. Gauthier-Rouvière C. Fort P. TrioGEF1 controls Rac- and Cdc42-dependent cell structures through the direct activation of rhoG. J. Cell Sci. 2000;113:729-739. [PubMed]Boureux A. Vignal E. Faure S. Fort P. Evolution of the rho family of ras-like GTPases in eukaryotes. Mol. Biol. Evol. 2007;24:203-216. [PMC free article] [PubMed]Cappello S. et al. The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface. Nat. Neurosci. 2006;9:1099-1107. [PubMed]Chen L. Liao G. Yang L. Campbell K. Nakafuku M. Kuan C. Y. Zheng Y. Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly. Proc. Natl. Acad. Sci. USA. 2006;103:16520-16525. [PMC free article] [PubMed]Chen L. Liao G. Waclaw R. R. Burns K. A. Linquist D. Campbell K. Zheng Y. Kuan C. Y. Rac1 controls the formation of midline commissures and the competency of tangential migration in ventral telencephalic neurons. J. Neurosci. 2007;27:3884-3893. [PubMed]Chen L. Melendez J. Campbell K. Kuan C. Y. Zheng Y. Rac1 deficiency in the forebrain results in neural progenitor reduction and microcephaly. Dev. Biol. 2009;325:162-170. [PMC free article] [PubMed]D’Angelo R. Aresta S. Blangy A. Del Maestro L. Louvard D. Arpin M. Conversation of ezrin with the novel guanine N-Methyl Metribuzin nucleotide exchange factor PLEKHG6 promotes RhoG-dependent apical cytoskeleton rearrangements in epithelial cells. Mol. Biol. Cell. 2007;18:4780-4793. [PMC free article] [PubMed]deBakker C. D. et al. Phagocytosis of apoptotic cells is usually regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. Curr. N-Methyl Metribuzin Biol. 2004;14:2208-2216. [PubMed]Dehay C. Kennedy H. Cell-cycle control and cortical development. Nat. Rev. Neurosci. 2007;8:438-450. [PubMed]Ellerbroek S. M. Wennerberg K. Arthur W. T. Dunty J. M. Bowman D. R. DeMali K. A. Der C. Burridge K. SGEF a RhoG guanine nucleotide exchange factor that stimulates macropinocytosis. Mol. Biol. Cell. 2004;15:3309-3319. [PMC free article] [PubMed]Engelman J. A. Luo J. Cantley L. C..