BRFAA - Biomedical Research Foundation Academy Of Athens
Biomedical Research Foundation Academy Of AthensAcademy Of Athens


Deciphering the Signaling Pathways that Shape a Cardiac Valve

The long-term goal of this project is to elucidate how cardiac valves form and function to support appropriate heart performance throughout the life of vertebrates. The heart is one of the first organs to form and function during vertebrate development. It starts functioning before its morphogenesis is completed. The central question that arises is how the morphogenetic changes and the functional changes during heart development are integrated. Cardiac valves derive from endocardial cells and form along the antero-posterior axis of the vertebrate heart to prevent retrograde blood flow. Valve morphogenesis happens while the heart is contracting and blood flows through the endocardium and it is influenced by shear stress on the endothelial cells. Defects in valve development affect 1% of the population and cause impaired heart function with lifelong complications. Studies in mouse and chick have been very informative in identifying key regulators and testing signaling pathways involved in valve development. However these studies are mainly in vitro and use predominantly reverse genetics approach. It is now obvious that our current knowledge will be significantly complemented by in vivo studies in zebrafish. In order to do that, we pursue multiple lines of research using complementary experimental approaches: a) the cloning of the remaining of the genes in the valve mutant lines we identified in a forward genetic screen; b) elucidate the signaling pathway of protein kinase D2 in angiogenesis and valve development c) the genome-wide analyses of the endothelial shear-stress sensing mechanisms in vivo; d) the functional analyses of the novel genes by reverse genetics; e) the generation of tools to study shear-stress and endothelial mechanical sensing in vivo; f) develop the tools and a framework to study adult valve maintenance and regeneration. We expect to develop a detailed framework of this fascinating but complex morphogenetic process which is crucial for cardiac function.


Cardiac valves form at the atrioventricular boundary and can be studied at the single-cell level in zebrafish


A zebrafish in vivo system to study cardiac valve regeneration