Gap junction adhesion is necessary for radial migration in the neocortex
Gap junction adhesion is necessary for radial migration in the neocortex
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DOI：
10.1038/nature06063
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发表时间：
2007-08-23
期刊：
影响因子：
64.8
通讯作者：
Kriegstein, Arnold R.
中科院分区：
文献类型：
--
作者：
Elias, Laura A. B.;Wang, Doris D.;Kriegstein, Arnold R.
放射状胶质细胞，胚胎大脑皮层的神经干细胞，存在于发育中的大脑深处，并将放射状纤维延伸到脑脊膜表面，胚胎神经元沿着放射状纤维迁移到皮层板。本研究表明，间隙连接亚基连接蛋白26 （Cx26）和连接蛋白43 （Cx43）在径向纤维和迁移神经元之间的接触点表达，Cx26或Cx43的急性下调会损害神经元向皮质板的迁移。出乎意料的是，间隙连接并没有通过传统的方式为细胞间的通信提供一个水通道来介导神经元的迁移。相反，间隙连接提供与内部细胞骨架相互作用的动态粘附接触，以实现沿径向纤维的领先过程稳定以及随后的细胞核易位。这些结果表明，间隙连接的粘附对于神经胶质引导的神经元迁移是必要的，这就提出了一种可能性，即间隙连接的粘附特性可能在与间隙连接功能相关的其他生理过程和疾病中发挥重要作用。
Radial glia, the neuronal stem cells of the embryonic cerebral cortex, reside deep within the developing brain and extend radial fibres to the pial surface, along which embryonic neurons migrate to reach the cortical plate. Here we show that the gap junction subunits connexin 26 (Cx26) and connexin 43 (Cx43) are expressed at the contact points between radial fibres and migrating neurons, and acute downregulation of Cx26 or Cx43 impairs the migration of neurons to the cortical plate. Unexpectedly, gap junctions do not mediate neuronal migration by acting in the classical manner to provide an aqueous channel for cell-cell communication. Instead, gap junctions provide dynamic adhesive contacts that interact with the internal cytoskeleton to enable leading process stabilization along radial fibres as well as the subsequent translocation of the nucleus. These results indicate that gap junction adhesions are necessary for glial-guided neuronal migration, raising the possibility that the adhesive properties of gap junctions may have an important role in other physiological processes and diseases associated with gap junction function.