The cellular basis of cardiac development and regeneration revealed by live imaging – liveheart

Heart pumping and shaping take place concomitantly during embryonic development. These two processes require a tight and dynamic coordination between mechanical forces and tissue morphogenesis. Importantly, in the adult, a cardiac disease or myocardial infarction can, sometimes very abruptly, alter cardiac contractily and cell composition. How mechanical parameters such as hemodynamic and tensile forces impact cardiac cells during disease is currently intensively investigated. While the mammalian heart undergoes primarily fibrotic repair, animals such as the zebrafish regenerate their heart completely upon different types of injury. The recently accepted fact that cardiomyocytes can also proliferate in adult mammals, including humans, even if only to a limited extent, makes it particularly important to understand how mechanical forces infer cardiac regeneration in species with high regenerative capacity.
To reach a comprehensive description of the organizational properties of different cardiac cell types during development and regeneration in a contracting organ such as the heart, we aim to study valve and epicardial formation based on a quantitative analysis of the biological and physical parameters operating at key steps of cardiogenesis. Our multidisciplinary approach will require expertise in biology, biomechanics, optics, and signal processing. We propose to develop high-resolution time- lapse imaging and optical approaches to collect biomechanical properties of the molecular, cellular and tissue dynamics underlying embryonic and adult heart development. This will be performed by visualizing embryonic and adult zebrafish hearts, with a specific focus on epicardium and valve formation. For the first time, we will assemble data at various scales to build a quantitative and quantitative analysis of the morphogenetic processes of heart valve and epicardium development at the cellular scale. This analysis will also enable us to test the biomechanical properties of the regenerating valve by comparison to the normal valve. A significant advantage of our live imaging analysis will be that it will allow for the quantitative features observed in vivo to be challenged using in silico heart models that we will develop in order to test the quality of heart function before and after regeneration.