Qin Rui, Cao Shuai, Lyu Tianjie, Qi Cai, Zhang Weiguang, Wang Yun
Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing 100191, China.
Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Cell Rep. 2017 Jan 10;18(2):380-390. doi: 10.1016/j.celrep.2016.12.043.
During brain development, the correct migration of newborn neurons is one of the determinants of circuit formation, and neuronal migration defects may lead to neurological and psychiatric disorders. The molecular mechanisms underlying neuronal migration and related disorders are poorly understood. Here, we report that Chromodomain Y-like (CDYL) is critical for neuronal migration in mice. Knocking down CDYL caused neuronal migration defects and disrupted both mobility and multipolar-to-bipolar transition of migrating neurons. We find that CDYL regulates neuronal migration by transcriptionally repressing RhoA. In addition, CDYL deficiency increased the excitability of cortical pyramidal neurons and the susceptibility of mice to convulsant-induced seizures. These results demonstrate that CDYL is a regulator of neuronal migration and shed light on the pathogenesis of seizure-related neurodevelopmental disorders.
在大脑发育过程中，新生神经元的正确迁移是神经回路形成的决定因素之一，而神经元迁移缺陷可能导致神经和精神疾病。目前对神经元迁移及相关疾病的分子机制了解甚少。在此，我们报告类Y染色体染色质结构域（CDYL）对小鼠神经元迁移至关重要。敲低CDYL会导致神经元迁移缺陷，并破坏迁移神经元的移动性和多极到双极的转变。我们发现CDYL通过转录抑制RhoA来调节神经元迁移。此外，CDYL缺乏会增加皮质锥体神经元的兴奋性以及小鼠对惊厥诱导癫痫发作的易感性。这些结果表明CDYL是神经元迁移的调节因子，并为癫痫相关神经发育障碍的发病机制提供了线索。
