Reelin and cofilin cooperate during the migration of cortical neurons: a quantitative morphological analysis
Reelin and cofilin cooperate during the migration of cortical neurons: a quantitative morphological analysis
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DOI：
10.1242/dev.134163
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发表时间：
2016-03-15
期刊：
影响因子：
4.6
通讯作者：
Frotscher, Michael
中科院分区：
文献类型：
--
作者：
Chai, Xuejun;Zhao, Shanting;Frotscher, Michael
在卷轴突变小鼠中，缺乏卷轴蛋白(Reln)，大脑皮层的分层被破坏。Reelin信号诱导LIM激酶1的磷酸化，使迁移神经元中的肌动蛋白解聚蛋白Cofilin磷酸化。条件性粘连蛋白突变体显示出神经元迁移缺陷。因此，卷轴蛋白和胶卷蛋白在皮质发育过程中都是不可或缺的。为了分析cofilin磷酸化对神经元迁移的影响，我们利用宫内电穿孔技术将编码非磷酸化cofilin 1(cofilin(S3A))、伪磷酸化cofilin 1(cofilin(S3E))或野生型cofilin 1(cofilin(WT))的pCAG-EGFP质粒导入E14.5野生型皮层神经元。将pCAG-EGFP基因导入野生型对照组和卷轴神经元。实时显微镜和组织学分析显示，cofilin WT和这两种磷酸化突变体的过表达导致了皮质神经元的迁移缺陷和形态异常。值得注意的是，卷绕神经元和Cofilin(S3A)和Cofilin(S3E)转基因神经元显示出向脑室区域异常的向后迁移。伪磷酸化形式CofilinS3E的过表达部分挽救了卷轴神经元的迁移缺陷，LIMK1的过表达也是如此。总而言之，这些结果表明，在神经元迁移过程中，reelin和cofilin在控制细胞骨架动力学方面起到了协同作用。
In reeler mutant mice, which are deficient in reelin (Reln), the lamination of the cerebral cortex is disrupted. Reelin signaling induces phosphorylation of LIM kinase 1, which phosphorylates the actin-depolymerizing protein cofilin in migrating neurons. Conditional cofilin mutants show neuronal migration defects. Thus, both reelin and cofilin are indispensable during cortical development. To analyze the effects of cofilin phosphorylation on neuronal migration we used in utero electroporation to transfect E14.5 wild-type cortical neurons with pCAG-EGFP plasmids encoding either a nonphosphorylatable form of cofilin 1 (cofilin(S3A)), a pseudophosphorylated form (cofilin(S3E)) or wild-type cofilin 1 (cofilin(WT)). Wild-type controls and reeler neurons were transfected with pCAG-EGFP. Real-time microscopy and histological analyses revealed that overexpression of cofilinWT and both phosphomutants induced migration defects and morphological abnormalities of cortical neurons. Of note, reeler neurons and cofilin(S3A)- and cofilin(S3E)-transfected neurons showed aberrant backward migration towards the ventricular zone. Overexpression of cofilinS3E, the pseudophosphorylated form, partially rescued the migration defect of reeler neurons, as did overexpression of Limk1. Collectively, the results indicate that reelin and cofilin cooperate in controlling cytoskeletal dynamics during neuronal migration.