Proper dendrite morphogenesis and neuronal migration are crucial for cerebral cortex development and neural circuit formation. In this study, we sought to determine if the histone deacetylase HDAC6 plays a role in dendrite development and neuronal migration of pyramidal neurons during cerebral cortex development. It was observed that knockdown of HDAC6 leads to defective dendrite morphogenesis and abnormal Golgi polarization in vitro, and the expression of wild type cortactin or deacetyl-mimetic cortactin 9KR rescued the defective phenotypes of the HDAC6 knockdown neurons. This suggests that HDAC6 promotes dendritic growth and Golgi polarization through cortactin deacetylation in vitro. We also demonstrated that ectopic expression of SIRT2, a cytoplasmic NAD+ − dependent deacetylase, suppresses the defects of HDAC6 knockdown neurons. These results indicate that HDAC6 and SIRT2 may be functionally redundant during dendrite development. Neurons transfected with both HDAC6 and SIRT2 shRNA or acetyl-mimetic cortactin 9KQ showed slow radial migration compared to the control cells during cerebral cortex development. Furthermore, a large portion of cortactin 9KQ-expressing pyramidal neurons at layer II/III in the cerebral cortex failed to form an apical dendrite toward the pial surface and had an increased number of primary dendrites, and the percentage of neurons with dendritic Golgi decreased in cortactin 9KQ-expressing cells, compared to control neurons. Taken together, this study suggests that HDAC6 and SIRT2 regulate neuronal migration and dendrite development through cortactin deacetylation in vivo.

中文翻译：

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HDAC6和SIRT2引起的cortactin脱乙酰作用在大脑皮质发育过程中调节神经元迁移和树突形态发生。

正确的树突形态发生和神经元迁移对于大脑皮层发育和神经回路形成至关重要。在这项研究中，我们试图确定组蛋白脱乙酰基酶HDAC6是否在大脑皮质发育过程中在树突发育和锥体神经元的神经元迁移中起作用。观察到，敲除HDAC6会导致缺陷的树突形态发生和体外高尔基极化异常，并且野生型Cortactin或脱乙酰基仿Cortactin 9KR的表达挽救了HDAC6敲除神经元的缺陷表型。这表明HDAC6在体外通过皮质激素脱乙酰基作用促进树突状生长和高尔基体极化。我们还证明了异位表达SIRT2，一种胞浆NAD +-依赖性脱乙酰基酶，可以抑制HDAC6敲低神经元的缺陷。这些结果表明，HDAC6和SIRT2在枝晶发育过程中可能在功能上是多余的。与HDAC6和SIRT2 shRNA或乙酰模拟的cortactin 9KQ一起转染的神经元与大脑皮层发育过程中的对照细胞相比显示出缓慢的径向迁移。此外，在大脑皮层的II / III层上，表达大量表达cortactin 9KQ的锥体神经元未能形成朝向顶表面的根尖树突，并且初级树突数量增加，而具有树突状高尔基体的神经元的百分比降低。与对照神经元相比，表达cortactin 9KQ的细胞。两者合计，这项研究表明HDAC6和SIRT2通过体内的皮质激素脱乙酰作用来调节神经元迁移和树突的发育。