Neurogenin 2 controls cortical neuron migration through regulation of Rnd2
Neurogenin 2 controls cortical neuron migration through regulation of Rnd2
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DOI：
10.1038/nature07198
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发表时间：
2008-09-04
期刊：
影响因子：
64.8
通讯作者：
Guillemot, Francois
中科院分区：
文献类型：
--
作者：
Heng, Julian Ik-Tsen;Nguyen, Laurent;Guillemot, Francois
运动性是新生神经元的普遍特性。细胞迁移如何与神经元产生的其他方面协调调节尚不清楚。在这里，我们发现控制胚胎大脑皮层神经发生的前神经蛋白神经原素2 （Neurog2）在新生小鼠皮层神经元开始迁移之前直接诱导小GTP结合蛋白Rnd2的表达（参考文献3）。Rnd2沉默导致皮质神经元径向迁移的缺陷，类似于Neurog2基因被删除时所观察到的。值得注意的是，恢复Rnd2在Neurog2突变神经元中的表达足以恢复它们的迁移能力。我们的研究结果确定了Rnd2是大脑皮层神经元迁移的一种新的重要调节剂，并证明Rnd2是促进迁移的Neurog2功能的主要效应器。因此，原膜蛋白通过一种非常直接的途径控制细胞迁移的复杂细胞行为，该途径涉及小GTP结合蛋白的转录激活。
Motility is a universal property of newly generated neurons. How cell migration is coordinately regulated with other aspects of neuron production is not well understood. Here we show that the proneural protein neurogenin 2 ( Neurog2), which controls neurogenesis in the embryonic cerebral cortex(1,2), directly induces the expression of the small GTP- binding protein Rnd2 ( ref. 3) in newly generated mouse cortical neurons before they initiate migration. Rnd2 silencing leads to a defect in radial migration of cortical neurons similar to that observed when the Neurog2 gene is deleted. Remarkably, restoring Rnd2 expression in Neurog2- mutant neurons is sufficient to rescue their ability to migrate. Our results identify Rnd2 as a novel essential regulator of neuronal migration in the cerebral cortex and demonstrate that Rnd2 is a major effector of Neurog2 function in the promotion of migration. Thus, a proneural protein controls the complex cellular behaviour of cell migration through a remarkably direct pathway involving the transcriptional activation of a small GTP- binding protein.