LKB1 regulates neuronal migration and neuronal differentiation in the developing neocortex through centrosomal positioning
LKB1 regulates neuronal migration and neuronal differentiation in the developing neocortex through centrosomal positioning
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DOI：
10.1523/jneurosci.1938-07.2007
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发表时间：
2007-10-24
影响因子：
5.3
通讯作者：
Fukada, Yoshitaka
中科院分区：
文献类型：
--
作者：
Asada, Naoyuki;Sanada, Kamon;Fukada, Yoshitaka
大脑皮层是通过高度有序的细胞过程（如神经元迁移和神经元成熟）的协同作用而形成的。神经元极性的建立以及神经元细胞骨架的极性调节对这些过程至关重要。在此我们发现，与秀丽隐杆线虫极性蛋白Par4最接近的同源物LKB1在发育中的新皮层中表达。在迁移的未成熟神经元中敲低LKB1会损害神经元迁移，导致中心体位置改变以及中心体与细胞核之间的解偶联。此外，在皮质板内分化的神经元中LKB1受损会导致中心体在细胞核基底面错误定位，而非正常的顶面定位。这伴随着轴突和树突极性的破坏，导致分化神经元的方向反转。而且，LKB1在体外可确定轴突和树突的特性。综上所述，这些观察结果表明LKB1在神经元迁移和神经元分化中起关键作用。此外，我们提出适当的神经元迁移和分化与LKB1所调控的中心体定位/移动的精确控制密切相关。
The cerebral cortex is formed through the coordination of highly organized cellular processes such as neuronal migration and neuronal maturation. Polarity establishment of neurons and polarized regulation of the neuronal cytoskeleton are essential for these events. Here we find that LKB1, the closest homolog of the Caenorhabditis elegans polarity protein Par4, is expressed in the developing neocortex. Knock-down of LKB1 in migrating immature neurons impairs neuronal migration, with alteration of the centrosomal positioning and with uncoupling between the centrosome and nucleus. Furthermore, impairment of LKB1 in differentiating neurons within the cortical plate induces malpositioning of the centrosome at the basal side of the nucleus, instead of the normal apical positioning. This is accompanied with the disruption of axonal and dendritic polarity, resulting in reversed orientation of differentiating neurons. Moreover, LKB1 specifies axon and dendrites identity in vitro. Together, these observations indicate that LKB1 plays a critical role in neuronal migration and neuronal differentiation. Furthermore, we propose that proper neuronal migration and differentiation are intimately coupled to the precise control of the centrosomal positioning/movement directed by LKB1.