RhoG promotes neural progenitor cell proliferation in mouse cerebral cortex.
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.
Fujimoto
Satoshi
S
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Negishi
Manabu
M
Katoh
Hironori
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D002867:Chromones / Q000378:metabolism; D018274:Electroporation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011247:Pregnancy; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D020741:rho GTP-Binding Proteins
D002867:Chromones; D004791:Enzyme Inhibitors; D020558:GTP Phosphohydrolases; D007381:Intermediate Filament Proteins; D009025:Morpholines; D009419:Nerve Tissue Proteins; D064231:Nestin; D019869:Phosphatidylinositol 3-Kinases; D020741:rho GTP-Binding Proteins; C577484:NES protein, human; C577485:Nes protein, mouse; C489577:Rhog protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one