Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development.
Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development.
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DOI：
10.1016/j.celrep.2016.04.027
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发表时间：
2016-05-17
期刊：
影响因子：
8.8
通讯作者：
Singh MK
中科院分区：
文献类型：
--
作者：
Singh A;Ramesh S;Cibi DM;Yun LS;Li J;Li L;Manderfield LJ;Olson EN;Epstein JA;Singh MK
冠状动脉血管的形成是一个复杂而精确协调的形态发生过程，始于心外膜的形成。心外膜产生冠状血管系统的许多组分，包括成纤维细胞、平滑肌细胞和内皮。河马信号成分与心脏发育和再生有关。然而，Hippo信号传导在心外膜中的作用尚未被探索。采用遗传学和药理学方法相结合，我们证明，抑制海马信号介质雅普和Taz导致受损的心外膜上皮细胞间质转化（EMT）和减少心外膜细胞增殖和分化为冠状动脉内皮细胞。我们提供的证据表明，雅普和塔兹控制心外膜细胞的行为，部分通过调节Tbx18和Wt1的表达。我们的研究结果显示了Hippo信号转导在心脏器官发生期间心外膜细胞增殖、EMT和细胞命运规范中的作用。
Formation of the coronary vasculature is a complex and precisely coordinated morphogenetic process that begins with the formation of epicardium. The epicardium gives rise to many components of the coronary vasculature, including fibroblasts, smooth muscle cells and endothelium. Hippo signaling components have been implicated in cardiac development and regeneration. However a role of Hippo signaling in the epicardium has not been explored. Employing a combination of genetic and pharmacological approaches, we demonstrate that inhibition of Hippo signaling mediators Yap and Taz leads to impaired epicardial epithelial-to-mesenchymal transition (EMT) and a reduction in epicardial cell proliferation and differentiation into coronary endothelial cells. We provide evidence that Yap and Taz control epicardial cell behavior, in part by regulating Tbx18 and Wt1 expression. Our findings show a role for Hippo signaling in epicardial cell proliferation, EMT and cell fate specification during cardiac organogenesis.