Hippo Signaling Mediators Yap and Taz Are Required in the Epicardium for Coronary Vasculature Development

• Published in: Cell reports (Cambridge) Vol. 15; no. 7; pp. 1384 - 1393
• Main Authors: Singh, Anamika, Ramesh, Sindhu, Cibi, Dasan Mary, Yun, Lim Sze, Li, Jun, Li, Li, Manderfield, Lauren J., Olson, Eric N., Epstein, Jonathan A., Singh, Manvendra K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-05-2016; Elsevier
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; Cell Cycle Proteins; Cell Differentiation; Cell Movement; Cell Proliferation; Coronary Vessels - cytology; Coronary Vessels - embryology; Coronary Vessels - metabolism; Embryo Loss - metabolism; Embryo Loss - pathology; Embryonic Development; Endothelial Cells - cytology; epicardium; epithelial to mesenchymal transition (EMT); Epithelial-Mesenchymal Transition; Gene Deletion; Gene Targeting; Green Fluorescent Proteins - metabolism; Hippo signaling; Integrases - metabolism; Mice, Knockout; Organogenesis; Pericardium - cytology; Pericardium - metabolism; Phosphoproteins - metabolism; proepicardium; Promoter Regions, Genetic - genetics; Protein-Serine-Threonine Kinases - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Semaphorins - metabolism; Signal Transduction; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Taz; Trans-Activators; WT1 Proteins; Yap; epicardium; Yap; proepicardium; Hippo signaling; Taz; epithelial to mesenchymal transition (EMT)
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.04.027

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.
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•Hippo signaling components are expressed in the developing proepicardium and epicardium•Genetic deletion of Yap and Taz leads to coronary vasculature defects•Yap and Taz regulate epicardial cell proliferation, EMT, and cell fate specification
Singh et al. show that Hippo signaling components are expressed in proepicardial and epicardial cells and are required for coronary vasculature development. Yap and Taz regulate epicardial cell proliferation, EMT, and cell fate specification, in part by regulating Tbx18 and Wt1 expression.