Negative regulation of Yap during neuronal differentiation.
Negative regulation of Yap during neuronal differentiation.
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DOI：
10.1016/j.ydbio.2011.10.017
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发表时间：
2012-01-01
影响因子：
2.7
通讯作者：
Turner DL
中科院分区：
文献类型：
--
作者：
Zhang H;Deo M;Thompson RC;Uhler MD;Turner DL
调节增殖和细胞周期退出是神经发生的重要方面。雅普转录辅激活因子在发育期间控制多种组织中的增殖，并且该活性由Hippo信号传导途径中的激酶负调控。我们发现雅普在有丝分裂的小鼠视网膜祖细胞中表达，并且在神经元分化过程中下调。出生后小鼠视网膜中雅普的强制表达可促进增殖，而通过RNA干扰（RNAi）抑制雅普可降低增殖并增加分化。我们发现雅普在视网膜中受到翻译后抑制，并且在mRNA表达水平上也下调。使用细胞培养模型，我们发现前神经碱性螺旋-环-螺旋（bHLH）转录因子Neurog 2或Ascl 1的表达下调雅普mRNA水平，同时通过激活Lats 1和/或Lats 2激酶抑制雅普蛋白。相反，过表达雅普阻止前神经bHLH蛋白启动细胞周期退出。我们建议，前神经bHLH蛋白和雅普之间的相互抑制是一个重要的调节增殖和细胞周期退出哺乳动物神经发生。
Regulated proliferation and cell cycle exit are essential aspects of neurogenesis. The Yap transcriptional coactivator controls proliferation in a variety of tissues during development, and this activity is negatively regulated by kinases in the Hippo signaling pathway. We find that Yap is expressed in mitotic mouse retinal progenitors and it is downregulated during neuronal differentiation. Forced expression of Yap prolongs proliferation in the postnatal mouse retina, whereas inhibition of Yap by RNA interference (RNAi) decreases proliferation and increases differentiation. We show Yap is subject to post-translational inhibition in the retina, and also downregulated at the level of mRNA expression. Using a cell culture model, we find that expression of the proneural basic helix-loop-helix (bHLH) transcription factors Neurog2 or Ascl1 downregulates Yap mRNA levels, and simultaneously inhibits Yap protein via activation of the Lats1 and/or Lats2 kinases. Conversely, overexpression of Yap prevents proneural bHLH proteins from initiating cell cycle exit. We propose that mutual inhibition between proneural bHLH proteins and Yap is an important regulator of proliferation and cell cycle exit during mammalian neurogenesis.
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影响因子：
2.7
作者：
Hufnagel RB;Le TT;Riesenberg AL;Brown NL
通讯作者：
Brown NL
影响因子：
14.9
作者：
Chung KH;Hart CC;Al-Bassam S;Avery A;Taylor J;Patel PD;Vojtek AB;Turner DL
通讯作者：
Turner DL
影响因子：
10.5
作者：
Bergsland, Maria;Werme, Martin;Muhr, Jonas
通讯作者：
Muhr, Jonas
影响因子：
64.8
作者：
BenArie, N;Bellen, HJ;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia