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

腺瘤性结肠息肉病2（APC 2）主要在神经系统中表达，并已知调节神经元中微管的稳定性。 我证明Apc 2的缺乏会导致大脑某些区域（包括大脑皮质和小脑）出现严重的分层缺陷。 在体内BrdU标记和免疫组化分析与特定的标志物表明，laminary异常是由于调节不良的神经元迁移的细胞自主机制。 小脑颗粒细胞的分析表明，BDNF刺激的定向迁移在Apc 2缺陷细胞受损。 我们发现，APC 2分布沿着肌动蛋白纤维以及微管的TIRF显微镜，和BDNF刺激的F-肌动蛋白的形成在前缘受损的Apc 2缺陷的神经元由于Rho GTdR活性失调。 这些结果表明，APC 2是响应细胞外信号的细胞骨架调节的重要介质。

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.