Developmental Cell
Volume 42, Issue 5, 11 September 2017, Pages 462-478.e7
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Article
YAP/TAZ Orchestrate VEGF Signaling during Developmental Angiogenesis

https://doi.org/10.1016/j.devcel.2017.08.002Get rights and content
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Highlights

  • YAP/TAZ activity is controlled by VEGF during angiogenesis

  • Endothelial expression of YAP/TAZ is essential for vascular system formation

  • VEGF induces a YAP/TAZ-dependent transcriptome linked to cytoskeleton remodeling

  • YAP/TAZ deletion results in impaired VEGFR2 cellular distribution and trafficking

Summary

Vascular endothelial growth factor (VEGF) is a major driver of blood vessel formation. However, the signal transduction pathways culminating in the biological consequences of VEGF signaling are only partially understood. Here, we show that the Hippo pathway effectors YAP and TAZ work as crucial signal transducers to mediate 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 and that activated YAP/TAZ induce a transcriptional program to further control cytoskeleton dynamics and thus establish a feedforward loop that ensures a proper angiogenic response. Lack of YAP/TAZ also results in altered cellular distribution of VEGFR2 due to trafficking defects from the Golgi apparatus to the plasma membrane. Altogether, our study identifies YAP/TAZ as central mediators of VEGF signaling and therefore as important regulators of angiogenesis.

Keywords

VEGF
VEGFR2
hippo pathway
YAP
TAZ
YAP/TAZ
angiogenesis
endothelial cells
CNS vascularization

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