YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development

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Item Type:

Article

Title:

YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development

Creators Name:

Neto, F. and Klaus-Bergmann, A. and Ong, Y.T. and Alt, S. and Vion, A.C. and Szymborska, A. and Carvalho, J.R. and Hollfinger, I. and Bartels-Klein, E. and Franco, C.A. and Potente, M. and Gerhardt, H.

Abstract:

Formation of blood vessel networks by sprouting angiogenesis is critical for tissue growth, homeostasis and regeneration. How endothelial cells arise in adequate numbers and arrange suitably to shape functional vascular networks is poorly understood. Here we show that YAP/TAZ promote stretch-induced proliferation and rearrangements of endothelial cells whilst preventing bleeding in developing vessels. Mechanistically, YAP/TAZ increase the turnover of VE-Cadherin and the formation of junction associated intermediate lamellipodia, promoting cell migration whilst maintaining barrier function. This is achieved in part by lowering BMP signalling. Consequently, the loss of YAP/TAZ in the mouse leads to stunted sprouting with local aggregation as well as scarcity of endothelial cells, branching irregularities and junction defects. Forced nuclear activity of TAZ instead drives hypersprouting and vascular hyperplasia. We propose a new model in which YAP/TAZ integrate mechanical signals with BMP signaling to maintain junctional compliance and integrity whilst balancing endothelial cell rearrangements in angiogenic vessels.

Source:

eLife

ISSN:

2050-084X

Publisher:

eLife Sciences Publications

Volume:

Page Range:

e31037

Date:

5 February 2018

Official Publication: