A Prdm8 target gene Ebf3 regulates multipolar-to-bipolar transition in migrating neocortical cells
A Prdm8 target gene Ebf3 regulates multipolar-to-bipolar transition in migrating neocortical cells
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Prdm8 靶基因 Ebf3 调节迁移新皮质细胞的多极到双极转变
DOI：
10.1016/j.bbrc.2017.11.021
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发表时间：
2018
影响因子：
3.1
通讯作者：
Mizutani Ken-ichi
中科院分区：
文献类型：
--
作者：
Iwai Ryota;Tabata Hidenori;Inoue Mayuko;Nomura Kei-ichiro;Okamoto Tadashi;Ichihashi Masamitsu;Nagata Koh-ichi;Mizutani Ken-ichi
神经元迁移的精确控制对于新皮质的发育至关重要。然而，神经元迁移的分子机制仍然很大程度上未知。在这里，我们将螺旋-环-螺旋转录因子 Ebf3 确定为 Prdm8 靶基因，并发现 Ebf3 是神经元通过多极到双极转变迁移的关键调节因子。 Ebf3 敲低细胞在主导过程的形成方面表现出严重缺陷，并且向运动模式的转变受到抑制。此外，我们发现 Ebf3 敲低抑制 NeuroD1 转录，而 NeuroD1 过表达部分挽救了 Ebf3 敲低细胞的迁移缺陷。我们的研究结果强调了 Ebf3 在发育中的新皮质中通过 NeuroD1 的正反馈调节在多极到双极转变中的关键作用。
Precise control of neuronal migration is essential for the development of the neocortex. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here we identified helix-loop-helix transcription factor Ebf3 as a Prdm8 target gene, and found that Ebf3 is a key regulator of neuronal migration via multipolar-to-bipolar transition. Ebf3 knockdown cells exhibited severe defects in the formation of leading processes and an inhibited shift to the locomotion mode. Moreover, we found that Ebf3 knockdown represses NeuroD1 transcription, and NeuroD1 overexpression partially rescued migration defects in Ebf3 knockdown cells. Our findings highlight the critical role of Ebf3 in multipolar-to-bipolar transition via positive feedback regulation of NeuroD1 in the developing neocortex.