Sakabe, M;
Fan, J;
Odaka, Y;
Liu, N;
Hassan, A;
Duan, X;
Stump, P;
... Xin, M; + view all
(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)
pp. 10918-10923.
10.1073/pnas.1704030114.
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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.
Type: | Article |
---|---|
Title: | YAP/TAZ-CDC42 signaling regulates vascular tip cell migration |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1073/pnas.1704030114 |
Publisher version: | http://dx.doi.org/10.1073/pnas.1704030114 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | Hippo signaling, angiogenesis, cell migration, CDC42 |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10044269 |
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