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Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):10918-10923. doi: 10.1073/pnas.1704030114. Epub 2017 Sep 25.

YAP/TAZ-CDC42 signaling regulates vascular tip cell migration.

Author information

1
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
2
Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH 45229.
3
Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
4
Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH 45229.
5
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
6
Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267.
7
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
8
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; Mei.Xin@cchmc.org.

Abstract

Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function. Finally, we found that cytoplasmic YAP positively regulated the activity of the small GTPase CDC42, deletion of which caused severe defects in endothelial migration. These findings uncover a previously unrecognized role of cytoplasmic YAP/TAZ in promoting cell migration by activating CDC42 and provide insight into how Hippo signaling in ECs regulates angiogenesis.

KEYWORDS:

CDC42; Hippo signaling; angiogenesis; cell migration

PMID:
28973878
PMCID:
PMC5642684
DOI:
10.1073/pnas.1704030114
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

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