Zhao Linnan, Li Jun, Ma Yuanlin, Wang Jiutao, Pan Wen, Gao Kai, Zhang Zhengrong, Lu Tianlan, Ruan Yanyan, Yue Weihua, Zhao Shanting, Wang Lifang, Zhang Dai
Peking University Sixth Hospital/Institute of Mental Health, Beijing 100191, China.
National Clinical Research Center for Mental Disorders/Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing 100191, China.
Sci Rep. 2015 Oct 26;5:15484. doi: 10.1038/srep15484.
Radial migration of pyramidal neurons is an important event during the development of cerebral cortex. Neurons experience series of morphological and directional transitions to get to their final laminar positions. Here we report that the histone methyltransferase enhancer of zest homolog 2 (Ezh2) is involved in the regulation of cortical radial migration. We show that Ezh2 knockdown leads to disturbed neuronal orientation, which results in the impairment of radial migration. Further results reveal that this migration deficiency may be due to the derepression of Reelin transcription in the migrating neurons. Our study provides evidence that epigenetic regulation of Reelin by Ezh2 maintains appropriate Reelin expression pattern to fulfill proper orientation of migrating neurons.
锥体神经元的放射状迁移是大脑皮质发育过程中的一个重要事件。神经元经历一系列形态和方向上的转变，以到达其最终的层状位置。在此，我们报告组蛋白甲基转移酶zeste同源物2增强子（Ezh2）参与皮质放射状迁移的调控。我们发现，敲低Ezh2会导致神经元方向紊乱，进而导致放射状迁移受损。进一步的结果表明，这种迁移缺陷可能是由于迁移神经元中Reelin转录的去抑制所致。我们的研究提供了证据，证明Ezh2对Reelin的表观遗传调控维持了适当的Reelin表达模式，以实现迁移神经元的正确定向。
