YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.
YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.
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DOI：
10.1038/nn.4316
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发表时间：
2016-07
影响因子：
25
通讯作者：
Feltri ML
中科院分区：
文献类型：
--
作者：
Poitelon Y;Lopez-Anido C;Catignas K;Berti C;Palmisano M;Williamson C;Ameroso D;Abiko K;Hwang Y;Gregorieff A;Wrana JL;Asmani M;Zhao R;Sim FJ;Wrabetz L;Svaren J;Feltri ML
髓鞘形成对神经系统功能至关重要。雪旺细胞与神经元和基底层相互作用，使用已知的受体、信号和转录因子来使轴突髓鞘化。相比之下，轴突分选的转录控制和机械转导在髓鞘形成中的作用在很大程度上尚不清楚。雅普和Taz是Hippo通路的效应子，在细胞中整合化学和机械信号。我们描述了一个以前未知的作用海马通路髓鞘形成。在小鼠中使用条件诱变，我们表明，Taz是需要在雪旺细胞的径向分选和髓鞘，和雅普是多余的Taz。雅普/Taz在雪旺细胞中被机械刺激激活，并调节雪旺细胞增殖和基底层受体基因的转录，这两者对于轴突的正确径向分选和随后的髓鞘形成都是必需的。这些数据将Hippo通路的转录效应子和施旺细胞中髓鞘形成的机械转导关联起来。
Myelination is essential for nervous system function. Schwann cells interact with neurons and the basal lamina to myelinate axons, using known receptors, signals and transcription factors. In contrast, the transcriptional control of axonal sorting and the role of mechanotransduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. We describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice we show that Taz is required in Schwann cells for radial sorting and myelination, and that Yap is redundant with Taz. Yap/Taz are activated in Schwann cells by mechanical stimuli, and regulate Schwann cell proliferation and transcription of basal lamina receptor genes, both necessary for proper radial sorting of axons and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells.