IQGAP1 regulates adult neural progenitors in vivo and vascular endothelial growth factor-triggered neural progenitor migration in vitro
IQGAP1 regulates adult neural progenitors in vivo and vascular endothelial growth factor-triggered neural progenitor migration in vitro
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DOI：
10.1523/jneurosci.0830-07.2007
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发表时间：
2007-04-25
影响因子：
5.3
通讯作者：
Baudier, Jacques
中科院分区：
文献类型：
--
作者：
Balenci, Laurent;Saoudi, Yasmina;Baudier, Jacques
在成年啮齿动物脑的萌发区，神经祖细胞迁移到由星形胶质细胞过程界定的壁龛中并分化成神经元前体。在本研究中，我们报告了支架蛋白IQGAP 1在神经祖细胞迁移中的调节作用。我们已经确定IQGAP 1作为一个新的标记物，扩增神经祖细胞和神经元前体细胞的脑室下区（SVZ）和吻侧迁移流（RMS）在成年小鼠大脑。为了确定IQGAP 1在神经祖细胞中的功能，我们比较了野生型和Iqgap 1缺失突变小鼠的神经祖细胞在体内和体外的特性。体内研究揭示了在Iqgap 1基因敲除小鼠中从头神经祖细胞向神经元前体细胞转变的延迟。在体外，我们证明了IQGAP 1在神经祖细胞的血管内皮生长因子（VEGF）依赖性迁移反应中作为下游效应子，也影响其神经元分化。Rho家族GTP酶cdc 42/Rac 1和Lis 1是IQGAP 1在这一迁移过程中的主要伙伴。最后，神经源性SVZ和RMS的星形胶质细胞表达VEGF。我们认为星形胶质细胞合成的VEGF可能参与神经祖细胞向神经源性龛的引导，IQGAP 1是VEGF依赖性迁移信号的效应子。
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.