αE-catenin inhibits YAP/TAZ activity to regulate signalling centre formation during tooth development.
αE-catenin inhibits YAP/TAZ activity to regulate signalling centre formation during tooth development.
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DOI：
10.1038/ncomms12133
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发表时间：
2016-07-13
影响因子：
16.6
通讯作者：
Klein OD
中科院分区：
文献类型：
--
作者：
Li CY;Hu J;Lu H;Lan J;Du W;Galicia N;Klein OD
胚胎信号中心是专门的非增殖细胞群，指导许多器官的发育。然而，在哺乳动物中建立这些基本结构的机制还不清楚。在这里，我们报告，使用小鼠切牙作为模型，α E-连环蛋白是必不可少的抑制核雅普定位和细胞增殖。α E-连环蛋白的这种功能是牙齿信号中心釉质结（EK）形成所必需的，该釉质结维持牙齿间充质凝聚和上皮内陷。EK的形成主要依赖于α E-连环蛋白通过雅普及其同源物TAZ的信号传导功能，而不是其粘附功能，并且雅普和TAZ的组合缺失挽救了由α E-连环蛋白缺失引起的EK缺陷。这些发现指出了一种发育机制，通过这种机制，α E-连环蛋白限制了雅普/TAZ的活性，以建立一组构成信号中心的非分裂和特化细胞。 目前还不清楚哪些信号调节牙齿信号中心，釉质结（EK）的建立。在这里，作者表明EK的形成依赖于α E-连环蛋白，其作用是限制Hippo途径转录因子Yes相关蛋白（雅普）和TAZ。
Embryonic signalling centres are specialized clusters of non-proliferating cells that direct the development of many organs. However, the mechanisms that establish these essential structures in mammals are not well understood. Here we report, using the murine incisor as a model, that αE-catenin is essential for inhibiting nuclear YAP localization and cell proliferation. This function of αE-catenin is required for formation of the tooth signalling centre, the enamel knot (EK), which maintains dental mesenchymal condensation and epithelial invagination. EK formation depends primarily on the signalling function of αE-catenin through YAP and its homologue TAZ, as opposed to its adhesive function, and combined deletion of Yap and Taz rescues the EK defects caused by loss of αE-catenin. These findings point to a developmental mechanism by which αE-catenin restricts YAP/TAZ activity to establish a group of non-dividing and specialized cells that constitute a signalling centre. It is unclear which signals regulate the establishment of the tooth signalling centre, the enamel knot (EK). Here, the authors show that EK formation depends on αE-catenin, which acts to restrict the Hippo pathway transcription factors Yes-associated protein (YAP) and TAZ.