Nature Neuroscience
- 9, 1099 - 1107 (2006)
Published online: 6 August 2006; | doi:10.1038/nn1744
The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surfaceSilvia Cappello1, Alessio Attardo2, Xunwei Wu3, Takuji Iwasato4, Shigeyoshi Itohara4, Michaela Wilsch-Bräuninger2, Hanna M Eilken1, Michael A Rieger1, Timm T Schroeder1, Wieland B Huttner2, Cord Brakebusch3 & Magdalena Götz1, 51
GSF, National Research Center for Environment and Health, Institute for Stem Cell Research, Ingolstädter Landstra e 1, D–85764 Neuherberg, Munich, Germany. 2
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany. 3
Institute of Molecular Pathology, Faculty of Health Sciences, University of Copenhagen, Frederik V's Vej 11, DK-2100, Copenhagen, Denmark. 4
Laboratory for Behavioral Genetics, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. 5
Institute of Physiology, University of Munich, Schillerstrasse 46, 80336 Munich, Germany.
Correspondence should be addressed to Magdalena Götz magdalena.goetz@gsf.de Stem cell persistence into adulthood requires self-renewal from early developmental stages. In the developing mouse brain, only apical progenitors located at the ventricle are self-renewing, whereas basal progenitors gradually deplete. However, nothing is known about the mechanisms regulating the fundamental difference between these progenitors. Here we show that the conditional deletion of the small Rho-GTPase cdc42 at different stages of neurogenesis in mouse telencephalon results in an immediate increase in basal mitoses. Whereas cdc42-deficient progenitors have normal cell cycle length, orientation of cell division and basement membrane contact, the apical location of the Par complex and adherens junctions are gradually lost, leading to an increasing failure of apically directed interkinetic nuclear migration. These cells then undergo mitoses at basal positions and acquire the fate of basal progenitors. Thus, cdc42 has a crucial role at the apical pole of progenitors, thereby regulating the position of mitoses and cell fate.
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