Elucidation of APC2 functions in the regulation of cytoskeletal dynamics during neuronal development

大肠腺瘤性息肉病2 （APC2）主要表达于神经系统，并调节神经元的微管稳定性。我展示了Apc2缺失会导致大脑某些区域严重的层状缺损包括大脑皮层和小脑。体内BrdU标记和特定标记物的免疫组织化学分析表明，层状结构异常是细胞自主机制下神经元迁移调节不良的结果。对小脑颗粒细胞的分析显示，bdnf刺激的定向迁移在apc2缺陷细胞中受损。我们通过TIRF显微镜发现APC2沿肌动蛋白纤维和微管分布，并且由于Rho GTPase活性失调，在APC2缺陷的神经元中，bdnf刺激的前沿f -肌动蛋白形成受损。这些结果表明，APC2是细胞骨架在响应细胞外信号的前沿调控的重要介质。

Adenomatous polyposis coli 2 (APC2) is mainly expressed in the nervous system and known to regulate microtubule stability in neurons. I show that a lack of Apc2 induces severe laminary defects in some regions of the brain including the cerebral cortex and cerebellum. In vivo BrdU labeling and immunohistochemical analyses with specific markers suggested that the laminary abnormalities are a result of poorly regulated neuronal migration by a cell-autonomous mechanism. Analyses of cerebellar granule cells revealed that the BDNF-stimulated directional migration is impaired in Apc2-deficient cells. We found that APC2 is distributed along actin fibers as well as microtubules by TIRF microscopy, and that BDNF-stimulated F-actin formation at the leading edge is impaired in Apc2-deficient neurons due to the dysregulation of Rho GTPase activity. These results suggest that APC2 is an essential mediator of the cytoskeletal regulation at leading edges in response to extracellular signals.