Objective
The epicardium is a mesothelial tissue that plays a crucial role during heart development, by contributing to the formation of cardiovascular precursor cells and by producing growth factors important for heart formation. Wt1 gene encodes a zinc finger protein, which plays a critical role in normal development of several organs such as kidney, gonads, spleen and heart. During heart formation, Wt1 is mainly expressed in the epicardium and epicardial derived cells. Deletion of Wt1 gene in an epicardial specific manner lead to a KO mouse with profound defect in both cardiomyocyte proliferation and coronary vascular development, suggesting that Wt1 KO epicardial cells constitute a good model to study the putative growth factors and signalling produced by epicardial cells. The principal objectives of the proposed project are to identify new targets of Wt1 during cardiovascular development, to explore their role in the formation of coronary blood vessels and cardiomyocyte proliferation and to dissect some of the mechanisms involved. We propose to study how Wt1 deletion, in vitro and in vivo, induced expression or repression of chemokines and growth factors and how this influences heart morphogenesis. The molecular mechanisms that regulate the development of the cardiovascular system in mouse embryos are comparable with those that regulate repair in adult tissue. The identification of new Wt1 targets during epicardium development, would allow us to design new strategies to activate those pathways during regeneration and repair of damaged hearts
Fields of science
Call for proposal
FP7-PEOPLE-2011-CIG
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Coordinator
08007 Barcelona
Spain