Endothelial RhoGEF Trio is involved in angiogenesis

Endothelial cells lining the vessel wall are instrumental in angiogenesis. They initiate this process and remodel their actin cytoskeleton to facilitate proliferation and migration from pre-existing vessels. However, the mechanisms that coordinate the remodeling of the endothelial actin cytoskeleton to promote angiogenesis are not fully understood. Here, we show that the RhoGEF Trio is involved in angiogenic sprouting in vitro and in vivo. Inhibition of Trio activity reduces sprout formation of intersomitic vessels in embryonic zebrafish. Moreover, a strong reduction in the length of developing sprouts is observed in a murine retinal explant assay. In addition, embryonic lethally Trio-/- mice show impaired disposition of the vasculature. Mechanistically, we show through rescue experiments that the N-terminal part of Trio, including the GEF1 domain, supported endothelial sprouting. Together, we conclude that Trio is involved in angiogenesis.