Hippo signaling mediators Yap and Taz are required in the epicardium for coronary vasculature development
Autor: | Sindhu Ramesh, Jonathan A. Epstein, Anamika Singh, Dasan Mary Cibi, Li Li, Lauren J. Manderfield, Lim Sze Yun, Manvendra K. Singh, Jun Li, Eric N. Olson |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
Taz
0301 basic medicine Cellular differentiation Organogenesis Cell Cycle Proteins Semaphorins 0302 clinical medicine Cell Movement epithelial to mesenchymal transition (EMT) epicardium Promoter Regions Genetic lcsh:QH301-705.5 Mice Knockout Cell Differentiation Anatomy Coronary Vessels Cell biology Hippo signaling Gene Targeting proepicardium cardiovascular system Embryo Loss Yap Signal transduction Pericardium Signal Transduction Epithelial-Mesenchymal Transition Green Fluorescent Proteins Embryonic Development Cell fate determination Biology Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Semaphorin Animals Hippo Signaling Pathway Epithelial–mesenchymal transition WT1 Proteins Adaptor Proteins Signal Transducing Cell Proliferation Integrases Cell growth Regeneration (biology) Endothelial Cells YAP-Signaling Proteins Phosphoproteins Repressor Proteins 030104 developmental biology lcsh:Biology (General) Trans-Activators T-Box Domain Proteins 030217 neurology & neurosurgery Gene Deletion |
Zdroj: | Cell Reports, Vol 15, Iss 7, Pp 1384-1393 (2016) |
Popis: | Summary: 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. : 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. Keywords: epicardium, proepicardium, Hippo signaling, Yap, Taz, epithelial to mesenchymal transition (EMT) |
Databáze: | OpenAIRE |
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