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. Wang et al. identify YAP/TAZ as essential co-transcription factors in endothelial cells during developmental angiogenesis. They describe that YAP/TAZ are activated by VEGF and that their activity is needed for transducing the VEGF signal into a specific transcriptional program, required for a full angiogenic response.

YAP/TAZ Orchestrate VEGF Signaling during Developmental Angiogenesis

Mazzone M.;
2017-01-01

Abstract

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. Wang et al. identify YAP/TAZ as essential co-transcription factors in endothelial cells during developmental angiogenesis. They describe that YAP/TAZ are activated by VEGF and that their activity is needed for transducing the VEGF signal into a specific transcriptional program, required for a full angiogenic response.
2017
angiogenesis
CNS vascularization
endothelial cells
hippo pathway
TAZ
VEGF
VEGFR2
YAP
YAP/TAZ
Actin Cytoskeleton
Adaptor Proteins
Signal Transducing
Animals
Animals
Newborn
Brain
Cell Cycle Proteins
Cell Line
Tumor
Cell Membrane
Cell Movement
Cell Nucleus
Chromatin Immunoprecipitation
Embryonic Development
Endothelial Cells
Gene Deletion
Gene Knockout Techniques
Gene Silencing
Golgi Apparatus
Mice
Models
Biological
Neovascularization
Pathologic
Phosphoproteins
Trans-Activators
Transcription
Genetic
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
YAP-Signaling Proteins
Neovascularization
Physiologic
Signal Transduction
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/83099
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