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

First Author  Sakabe M Year  2017
Journal  Proc Natl Acad Sci U S A Volume  114
Issue  41 Pages  10918-10923
PubMed ID  28973878 Mgi Jnum  J:280139
Mgi Id  MGI:6095458 Doi  10.1073/pnas.1704030114
Citation  Sakabe M, et al. (2017) YAP/TAZ-CDC42 signaling regulates vascular tip cell migration. Proc Natl Acad Sci U S A 114(41):10918-10923
abstractText  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.
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