An essential role for YAP/TAZ in developmental and pathogenic angiogenesis

During angiogenesis, growth factors stimulate differentiation of endothelial cells and coordinate their sprouting, migration, and assembly into vessels. While the major ligands and receptors that regulate angiogenesis have been identified, the transcriptional factors that underpin these complex signaling processes are not well defined. This week in the JCI, a study led by Gou Young Koh at the Korea Advanced Institute of Science and Technology reveals that sprouting angiogenesis, migration, vascular barrier maturation, and endothelial cell metabolism require YAP/TAZ expression.

YAP/TAZ acts as an effector of the Hippo signaling pathway and has previously been implicated in controlling structural and functional maturation in endothelial cells. In the present study, researchers observed high levels of YAP/TAZ expression in the murine retina and brain during the early postnatal period. Selective deletion of Yap/Taz in endothelial cells disrupted vascular network formation in these regions, resulting in blunted endothelial cell sprouting and an overly pruned vascular network (see the accompanying images). Yap/Taz deletion also impaired pathological remodeling of vascular networks in a mouse model of macular degeneration, suggesting that YAP/TAZ may also regulate angiogenesis in disease states. Mechanistically, the researchers discovered that YAP/TAZ supports multiple angiogenic processes by activating actin remodeling and MYC signaling in endothelial cells, supporting structural maturation and metabolic activity, respectively.

The accompanying images highlight the essential role of YAP/TAZ in coordinating angiogenesis in the striatum and cortex (top) and retina (bottom). Endothelial cells lacking YAP/TAZ (right) displayed profound defects in vascular network formation, with blunted sprouting, enhanced pruning, and impairments in junction and barrier integrity. 

Scientific Show Stopper