YAP/TAZ regulates sprouting angiogenesis and vascular barrier maturation

Area of Science:

• Vascular Biology
• Molecular Biology
• Cell Biology

Background:

• Angiogenesis is essential for forming new blood vessels, involving coordinated endothelial cell (EC) behaviors.
• While signaling pathways are known, key transcriptional regulators of ECs in angiogenesis are emerging.
• YAP/TAZ, effectors of the Hippo signaling pathway, are investigated for their role in EC function.

Purpose of the Study:

• To elucidate the role of YAP/TAZ in sprouting angiogenesis and vascular barrier formation.
• To understand the mechanistic basis of YAP/TAZ function in endothelial cells.

Main Methods:

• Endothelial-specific deletion of Yap/Taz in mice.
• Analysis of vascular morphology, EC behavior, and protein localization in retinal and brain vessels.
• Investigation of YAP/TAZ-mediated signaling pathways, including actin cytoskeleton and MYC signaling.

Main Results:

• Endothelial Yap/Taz deletion caused defective tip ECs, pruned vasculature, and disrupted endothelial junctions.
• Loss of YAP/TAZ led to impaired barrier integrity, hemorrhage, and reduced pathological angiogenesis.
• YAP/TAZ promotes actin remodeling, EC proliferation, and metabolic activity via MYC signaling.

Conclusions:

• YAP/TAZ are critical regulators of sprouting angiogenesis, vascular barrier integrity, and EC metabolism.
• YAP/TAZ orchestrate multiple EC behaviors, including migration, proliferation, and junction formation.
• YAP/TAZ represent a potential therapeutic target for neovascular diseases.