YAP/TAZ-CDC42 signaling regulates vascular tip cell migration

Masahide Sakabe, Jieqing Fan, Yoshinobu Odaka, Ning Liu, Aishlin Hassan, Xin Duan, Paige Stump, Luke Byerly, Megan Donaldson, Jiukuan Hao, Marcus Fruttiger, Qing Richard Lu, Yi Zheng, Richard A. Lang, Mei Xin

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10918-10923
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number41
DOIs
StatePublished - Oct 10 2017

Keywords

  • Angiogenesis
  • CDC42
  • Cell migration
  • Hippo signaling

ASJC Scopus subject areas

  • General

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  • Cite this

    Sakabe, M., Fan, J., Odaka, Y., Liu, N., Hassan, A., Duan, X., Stump, P., Byerly, L., Donaldson, M., Hao, J., Fruttiger, M., Lu, Q. R., Zheng, Y., Lang, R. A., & Xin, M. (2017). YAP/TAZ-CDC42 signaling regulates vascular tip cell migration. Proceedings of the National Academy of Sciences of the United States of America, 114(41), 10918-10923. https://doi.org/10.1073/pnas.1704030114