Heng Julian Ik-Tsen, Nguyen Laurent, Castro Diogo S, Zimmer Céline, Wildner Hendrik, Armant Olivier, Skowronska-Krawczyk Dorota, Bedogni Francesco, Matter Jean-Marc, Hevner Robert, Guillemot François
Division of Molecular Neurobiology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Nature. 2008 Sep 4;455(7209):114-8. doi: 10.1038/nature07198.
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, 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.
神经元迁移是新生成神经元的普遍特性。细胞迁移如何与神经元生成的其他方面协同调控，目前尚不清楚。在此，我们表明，在胚胎大脑皮层中控制神经发生的神经前体细胞蛋白神经生成素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（参考文献3）的表达。Rnd2沉默导致皮层神经元的放射状迁移缺陷，类似于Neurog2基因缺失时观察到的情况。值得注意的是，在Neurog2突变神经元中恢复Rnd2表达足以挽救其迁移能力。我们的研究结果确定Rnd2是大脑皮层神经元迁移的一种新型关键调节因子，并证明Rnd2是Neurog2在促进迁移功能中的主要效应器。因此，一种神经前体细胞蛋白通过一条涉及小GTP结合蛋白转录激活的非常直接的途径，控制细胞迁移这一复杂的细胞行为。
