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

腺瘤性息肉病结肠2(APC2)主要在神经系统表达，对神经元的微管稳定性有调节作用。我的研究表明，缺乏Apc2会导致大脑某些区域出现严重的层状缺陷，包括大脑皮层和小脑。体内BrdU标记和具有特定标记的免疫组织化学分析表明，板层异常是细胞自主机制对神经元迁移调控不力的结果。对小脑颗粒细胞的分析表明，在Apc2缺乏的细胞中，BDNF刺激的定向迁移受到损害。在TIRF显微镜下，我们发现APC2分布在肌动蛋白纤维和微管上，而在Apc2缺乏的神经元中，由于Rho GTPase活性的失调，BDNF刺激的前缘F-肌动蛋白的形成受到了损害。这些结果表明，APC2是响应细胞外信号的前沿细胞骨架调节的重要中介。

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.