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The Journal of Neuroscience, April 25, 2007, 27(17):4716-4724; doi:10.1523/JNEUROSCI.0830-07.2007

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Cellular/Molecular
IQGAP1 Regulates Adult Neural Progenitors In Vivo and Vascular Endothelial Growth Factor-Triggered Neural Progenitor Migration In Vitro

Laurent Balenci,^1,2,3 Yasmina Saoudi,^2,3,4 Didier Grunwald,^1,2,3 Jean Christophe Deloulme,^1,2,3 Alexandre Bouron,^2,5 André Bernards,⁶ and Jacques Baudier^1,2,3

¹Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 873, Laboratoire Transduction du Signal, F-38054 Grenoble, France, ²Commissariat à l'Energie Atomique, Institut de Recherche en Technologies et Sciences pour le Vivant, F-38054 Grenoble, France, ³Université Joseph Fourier, F-38054 Grenoble, France, ⁴INSERM, Unité 836, Groupe de Physiopathologie du Cytosquelette, F-38054 Grenoble, France, ⁵Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5249, Laboratoire de Chimie et Biologie des Métaux, F-38054 Grenoble, France, and ⁶Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129

Correspondence should be addressed to Dr. Jacques Baudier, Unité 873/Transduction du Signal-Institut de Recherche en Technologies et Sciences pour le Vivant, Commissariat à l'Energie Atomique Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France. Email: jbaudier{at}cea.fr

In the germinative zone of the adult rodent brain, neural progenitors migrate into niches delimited by astrocyte processes and differentiate into neuronal precursors. In the present study, we report a modulating role for the scaffolding protein IQGAP1 in neural progenitor migration. We have identified IQGAP1 as a new marker of amplifying neural progenitor and neuronal precursor cells of the subventricular zone (SVZ) and the rostral migratory stream (RMS) in the adult mouse brain. To determine functions for IQGAP1 in neural progenitors, we compared the properties of neural progenitor cells from wild-type and Iqgap1-null mutant mice in vivo and in vitro. The in vivo studies reveal a delay in the transition of de novo neural progenitors into neuronal precursor cells in Iqgap1-null mice. In vitro, we demonstrated that IQGAP1 acts as a downstream effector in the vascular endothelial growth factor (VEGF)-dependent migratory response of neural progenitors that also impacts on their neuronal differentiation. The Rho-family GTPases cdc42/Rac1 and Lis1 are major partners of IQGAP1 in this migratory process. Finally, astrocytes of the neurogenic SVZ and RMS are shown to express VEGF. We propose that VEGF synthesized by astrocytes could be involved in the guidance of neural progenitors to neurogenic niches and that IQGAP1 is an effector of the VEGF-dependent migratory signal.

Key words: adult neurogenesis; IQGAP1; migration; neural progenitors; Rac1/Cdc42; VEGF

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Received Sept. 26, 2006; accepted March 16, 2007.

Correspondence should be addressed to Dr. Jacques Baudier, Unité 873/Transduction du Signal-Institut de Recherche en Technologies et Sciences pour le Vivant, Commissariat à l'Energie Atomique Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France. Email: jbaudier{at}cea.fr

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