@article{e52b833131ca4167a32905692bb38a57,
title = "Vinculin controls endothelial cell junction dynamics during vascular lumen formation",
abstract = "Blood vessel morphogenesis is driven by coordinated endothelial cell behaviors. Active remodeling of cell-cell junctions promotes cellular plasticity while preserving vascular integrity. Here, we analyze the dynamics of endothelial adherens junctions during lumen formation in angiogenic sprouts in vivo. Live imaging in zebrafish reveals that lumen expansion is accompanied by the formation of transient finger-shaped junctions. Junctional fingers are positively regulated by blood pressure, whereas flow inhibition prevents their formation. Using fluorescent reporters, we show that junctional fingers contain the mechanotransduction protein vinculin. Furthermore, genetic deletion of vinculin prevents finger formation, a junctional defect that could be rescued by transient endothelial expression of vinculin. Our findings suggest a mechanism whereby lumen expansion leads to an increase in junctional tension, triggering recruitment of vinculin and formation of junctional fingers. We propose that endothelial cells employ force-dependent junctional remodeling to counteract external forces in order to maintain vascular integrity during sprouting angiogenesis.",
keywords = "CP: Cell biology, VE-cadherin, angiogenesis, cell-cell adhesion, junctional dynamics, lumenization, vinculin, zebrafish",
author = "Kotini, {Maria P.} and {van der Stoel}, {Miesje M.} and Jianmin Yin and Han, {Mitchell K.} and Bettina Kirchmaier and {de Rooij}, Johan and Markus Affolter and Stephan Huveneers and Heinz-Georg Belting",
note = "Funding Information: We thank Kumuthini Kulendra for fish care and the Imaging Core Facility of the Biozentrum (University of Basel) for microscopy support. This work has been supported by the Kantons Basel-Stadt and Basel-Land and by grants from the Swiss National Science Foundation (310030_200701 and 310030B_176400) to M.A. S.H. is financially supported by the Netherlands Organization of Scientific Research (NWO)-ZonMw VIDI grant 016.156.327. M.M.v.d.S. was financially supported by the European Zebrafish Society and University of Amsterdam (UvA365). H.-G.B. and S.H. conceived the idea and directed the work. M.A. provided supervision and financial support. M.P.K. and M.M.v.d.S. designed and performed experiments. J.Y. performed experiments. H.-G.B. S.H. M.A. M.P.K. and M.M.v.d.S. analyzed the data. M.K.H. B.K. and J.d.R. provided essential reagents. M.P.K. and M.M.v.d.S. prepared figures. H.-G.B. S.H. M.P.K. and M.M.v.d.S. wrote the manuscript. All authors reviewed the manuscript. The authors declare no competing interests. Funding Information: We thank Kumuthini Kulendra for fish care and the Imaging Core Facility of the Biozentrum (University of Basel) for microscopy support. This work has been supported by the Kantons Basel-Stadt and Basel-Land and by grants from the Swiss National Science Foundation (310030_200701 and 310030B_176400) to M.A. S.H. is financially supported by the Netherlands Organization of Scientific Research (NWO)-ZonMw VIDI grant 016.156.327 . M.M.v.d.S. was financially supported by the European Zebrafish Society and University of Amsterdam (UvA365) . Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = apr,
day = "12",
doi = "https://doi.org/10.1016/j.celrep.2022.110658",
language = "English",
volume = "39",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",
}