Identifying new regulators of cardiovascular development

This thesis provides the first in vivo characterization of dlc1, dlc3 and cndp2 during embryonic development in zebrafish. Dlc1 and dlc3 play a crucial role in vasculogenic, angiogenic and cardiogenic processes. Both genes impair the growth of intersegmental vessels and the common cardinal veins, indicating an important role for dlc's in endothelial cell migration during angiogenic sprouting. The observed phenotypes could be linked to dlc1's RhoGAP activity on RhoA and the VEGF-A/flk1/Nrp1 signaling axis. Moreover, dlc1 negatively affects the lumenization of the first aortic arch arteries, the lateral dorsal aortae and proper outflow tract development. Cndp2 is enriched in endothelial cells in the CHT and in macrophages. Whereas overepression of cndp2 showed an impaired caudal vein plexus formation, loss of cndp2 impaired HSC survival in the endothelial niche and reduced HSC numbers in the thymus. This decrease in HSC survival was independent of nitric oxide or reactive oxygen species-dependent mechanisms and requires further investigation