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Vol. 20, Issue 23, 4941-4950, December 1, 2009

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RhoG Promotes Neural Progenitor Cell Proliferation in Mouse Cerebral Cortex

Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan

Submitted March 11, 2009; Revised September 8, 2009; Accepted September 25, 2009
Monitoring Editor: J. Silvio Gutkind

In early cortical development, neural progenitor cells (NPCs) expand their population in the ventricular zone (VZ), and produce neurons. Although a series of studies have revealed the process of neurogenesis, the molecular mechanisms regulating NPC proliferation are still largely unknown. Here we found that RhoG, a member of Rho family GTPases, was expressed in the VZ at early stages of cortical development. Expression of constitutively active RhoG promoted NPC proliferation and incorporation of bromodeoxyuridine (BrdU) in vitro, and the proportion of Ki67-positive cells in vivo. In contrast, knockdown of RhoG by RNA interference suppressed the proliferation, BrdU incorporation, and the 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 interaction with ELMO. Taken together, these results indicate that RhoG promotes NPC proliferation through PI3K in cortical development.

Address correspondence to: Hironori Katoh (hirokato{at}pharm.kyoto-u.ac.jp).

Abbreviations used: BrdU, bromodeoxyuridine; CP, cortical plate; IZ, intermediate zone; NPC, neural progenitor cell; PI3K, phosphatidylinositol 3-kinase; shRNA, short hairpin RNA; SVZ, subventricular zone; VZ, ventricular zone.