"The cardiovascular system is vital to every vertebrate and is the first functional organ in the developing embryo. As a consequence, the heartbeats generate hemodynamic forces that physically stimulate growing arteries and veins at the earliest steps of cardiovascular development. The mechanisms involved in vascular morphogenesis are poorly understood. One of the fundamental questions is whether vascular morphogenesis depends solely on genetic pre-programming or whether additional environmental cues provided by blood flow are needed. To date, the experimental data are few and somewhat controversial. This might be due to the fact that understanding of the roles of hemodynamic forces is challenging since flow patterns are highly dynamic and only accessible in live embryos. Thus, addressing the contribution of blood flow during cardiovascular development not only necessitates imaging techniques to visualize and quantify the flow forces but also proper experimental methods to alter and modify them in vivo. Primarily, this proposal is focused on developing fast imaging approaches allowing the visualization of blood flow patterns in specific regions of the cardiovascular system and the effect flow altering treatments on endothelial cells at different developmental stages. Secondarily, these experiments will be combined with molecular biology techniques to identify the genes activated by flows and conventional imaging to characterize the effects of flow alterations. In particular, we will develop live flow reporters to correlate the flow response with gene expression in vivo. The insights gained from these in vivo studies will significantly increase our knowledge on how genetic networks interact with their physical environment during vascular development. Ultimately, this work should lead to relevant findings for a better understanding of congenital cardiovascular diseases."