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神经干细胞增殖调控机理获新进展

来源:生物谷 2014-09-10 09:04

2014年9月10日 讯 /,中科院生物物理研究所脑与认知科学国家重点实验室袁增强研究组在著名期刊《神经科学杂志》(The Journal of Neuroscience)上在线发表了标题为“BMP2-SMAD Signaling Represses the Proliferation ofEmbryonic Neural Stem Cells through YAP”,报道了关于YAP参与BMP信号通路对胚胎神经干细胞增殖调控的重要进展,该研究首次揭示了在胚胎神经干细胞增殖调控中BMP信号通路与Hippo-YAP信号通路交联所扮演的角色。

神经干/祖细胞(Neural Stem/Progenitor Cells, NSPC)的增殖维持和分化是神经发生的重要环节,阐明其分子机制不仅有助于解释神经发生的过程,而且能为衰老以及神经系统损伤和神经退行性疾病的细胞治疗提供理论基础。此前研究显示Hippo通路与TAP通路的交联在保持干细胞繁殖过程中起到了重要作用。然而对于这一过程中的分子机制,科学家到现在都不太清楚。袁增强等人发现了YAP在胚胎神经干细胞增殖调控中的重要功能。袁增强研究组发现YAP参与BMPs 信号对 NSPC 增殖的调控。BMPs 信号活化的Smad复合体,竞争性与 YAP结合,抑制 YAP/TEAD 复合体调控的下游增殖相关基因ccnd1的表达,从而最终抑制了 NSPC 的增殖。这一研究在阐明BMP信号通路与Hippo-YAP信号通路交联分子机制的同时,也表明这一分子机制可能为衰老和神经退行性疾病的细胞治疗提供新型靶标。(生物谷Bioon.com)

生物谷推荐的英文摘要:

The Journal of Neuroscience      

doi: 10.1523/JNEUROSCI.0486-14.2014

BMP2-SMAD Signaling Represses the Proliferation of Embryonic Neural Stem Cells through YAP

Minghui Yao, Yadong Wang, Peng Zhang, Hong Chen, Zhiheng Xu, Jianwei Jiao, and Zengqiang Yuan

Previous studies have shown that the Hippo pathway effector yes-associated protein (YAP) plays an important role in maintaining stem cell proliferation. However, the precise molecular mechanism of YAP in regulating murine embryonic neural stem cells (NSCs) remains largely unknown. Here, we show that bone morphogenetic protein-2 (BMP2) treatment inhibited the proliferation of mouse embryonic NSCs, that YAP was critical for mouse NSC proliferation, and that BMP2 treatment-induced inhibition of mouse NSC proliferation was abrogated by YAP knockdown, indicating that the YAP protein mediates the inhibitory effect of BMP2 signaling. Additionally, we found that BMP2 treatment reduced YAP nuclear translocation, YAP-TEAD interaction, and YAP-mediated transactivation. BMP2 treatment inhibited YAP/TEAD-mediated Cyclin D1 (ccnd1) expression, and knockdown of ccnd1 abrogated the BMP2-mediated inhibition of mouse NSC proliferation. Mechanistically, we found that Smad1/4, effectors of BMP2 signaling, competed with YAP for the interaction with TAED1 and inhibited YAP's cotranscriptional activity. Our data reveal mechanistic cross talk between BMP2 signaling and the Hippo-YAP pathway in murine NSC proliferation, which may be exploited as a therapeutic target in neurodegenerative diseases and aging.

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