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
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