Mechanisms that Govern Endothelial Lineage Development and Vasculogenesis

Vascular diseases have considerable morbidity and mortality. Current therapies for these diseases are limited and therefore it is essential to define the hierarchy of gene expression that regulates vasculogenesis as a platform for future interventions. In this chapter, we highlight the role of ETV2, which functions as a master regulator for the hematoendothelial and vascular lineages. The global deletion of Etv2 in zebrafish, mouse and pig demonstrate embryonic lethality due to the absence of blood and vasculature lineages. Further, overexpression of ETV2 reprograms cells to the hematoendothelial lineages and represses the fate of other lineages. ETV2 functions to regulate downstream targets thereby modulating fate decisions, cell proliferation, cell migration, and apoptosis to impact vascular development in response to physiological stimuli, tissue injury and tumorigenesis. Targeted strategies aimed at inducing or repressing ETV2 expression may serve as a platform for medical therapeutic interventions for vascular diseases.