Project description:VEGF is a major driver of blood vessel formation. However, the signal transduction pathways culminating into the biological consequences of VEGF signaling are partially understood. Here we show that the Hippo pathway effectors YAP and TAZ, work as a regulatory hub in mediating VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality. Mechanistically, we show that VEGF activates YAP/TAZ via its effects on actin cytoskeleton remodeling, and that activated YAP/TAZ induce a transcriptional program that results in the expression of a set of genes to further control cytoskeleton dynamics, and thus ensure a proper angiogenic response. YAP/TAZ deletion also results in VEGFR2 trafficking defects from the Golgi to the plasma membrane. Together, our study establishes YAP/TAZ as a central regulatory hub that mediates VEGF signaling, and hence, regulates angiogenesis.
Project description:VEGF is a major driver of blood vessel formation. However, the signal transduction pathways culminating into the biological consequences of VEGF signaling are partially understood. Here we show that the Hippo pathway effectors YAP and TAZ, work as a regulatory hub in mediating VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality. Mechanistically, we show that VEGF activates YAP/TAZ via its effects on actin cytoskeleton remodeling, and that activated YAP/TAZ induce a transcriptional program that results in the expression of a set of genes to further control cytoskeleton dynamics, and thus ensure a proper angiogenic response. YAP/TAZ deletion also results in VEGFR2 trafficking defects from the Golgi to the plasma membrane. Together, our study establishes YAP/TAZ as a central regulatory hub that mediates VEGF signaling, and hence, regulates angiogenesis.
