Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex
Drebrin-like (Dbnl) Controls Neuronal Migration via Regulating N-Cadherin Expression in the Developing Cerebral Cortex
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DOI：
10.1523/jneurosci.1634-18.2018
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发表时间：
2019-01-23
影响因子：
5.3
通讯作者：
Nakajima, Kazunori
中科院分区：
文献类型：
--
作者：
Inoue, Seika;Hayashi, Kanehiro;Nakajima, Kazunori
肌动蛋白细胞骨架对哺乳动物大脑皮层发育中的神经元迁移至关重要。接头蛋白Drebrin-like（Dbnl）通过与F-actin、cobl和dynamin相互作用，在肌动蛋白细胞骨架的重组、树突的形成和内吞作用中起重要作用。虽然已知Dbnl在大脑中表达，但该分子在大脑发育期间的功能在很大程度上是未知的。在这项研究中，研究Dbnl在发育中的大脑皮层的作用，我们进行了实验，使用小鼠的两种性别的Dbnl敲低，在子宫内电穿孔的影响，在胚胎皮层的迁移神经元。Dbnl敲低的神经元的延时成像显示Dbnl的存在是在多极细胞聚集区或室下区的深部中的多极神经元中适当形成过程以及神经元极化和进入皮质板的先决条件。我们发现Dbnl基因敲低降低了皮层神经元质膜上N-钙粘蛋白的表达量。Dbnl敲低引起的神经元迁移缺陷通过N-钙粘蛋白和α-N-连环蛋白的中度过表达或Dbnl的磷酸模拟形式（Y337 E，Y347 E）而不是磷酸抗性形式（Y337 F，Y347 F）的转染来挽救。这些结果表明，Dbnl控制神经元迁移，神经元多极形态，和细胞极性在发育中的大脑皮层通过调节N-钙粘蛋白的表达。
The actin cytoskeleton is crucial for neuronal migration in the mammalian developing cerebral cortex. The adaptor protein Drebrin-like (Dbnl) plays important roles in reorganization of the actin cytoskeleton, dendrite formation, and endocytosis by interacting with F-actin, cobl, and dynamin. Although Dbnl is known to be expressed in the brain, the functions of this molecule during brain development are largely unknown. In this study, to examine the roles of Dbnl in the developing cerebral cortex, we conducted experiments using mice of both sexes with knockdown of Dbnl, effected by in utero electroporation, in the migrating neurons of the embryonic cortex. Time-lapse imaging of the Dbnl-knockdown neurons revealed that the presence of Dbnl is a prerequisite for appropriate formation of processes in the multipolar neurons in the multipolar cell accumulation zone or the deep part of the subventricular zone, and for neuronal polarization and entry into the cortical plate. We found that Dbnl knockdown decreased the amount of N-cadherin protein expressed on the plasma membraneof the cortical neurons. The defect in neuronal migration caused by Dbnl knockdown was rescued by moderate overexpression of N-cadherin and alpha N-catenin or by transfection of the phospho-mimic form (Y337E, Y347E), but not the phospho-resistant form (Y337F, Y347F), of Dbnl. These results suggest that Dbnl controls neuronal migration, neuronal multipolar morphology, and cell polarity in the developing cerebral cortex via regulating N-cadherin expression.