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

Item Type:

Preprint

Title:

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 a hierarchically organized blood vessel network by sprouting angiogenesis is critical for tissue growth, homeostasis and regeneration. How in this process endothelial cells arise in adequate numbers and arrange suitably to shape a functional vascular network is poorly understood. Here we show that YAP and TAZ promote stretch-induced proliferation and rearrangements of endothelial cells whilst preventing bleeding in developing vessels. Mechanistically, YAP and TAZ increase VE-cadherin turnover at junctions and suppress endothelial Notch and BMP signaling, two key pathways that limit sprouting and endothelial dynamics. Consequently, the loss of YAP and TAZ 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 and TAZ integrate mechanical signals with Notch and BMP signaling to balance endothelial cell distribution in angiogenic vessels.

Keywords:

Endothelial Cells, YAP, TAZ, VE-Cadherin, Adherens Junctions, Vascular Development, Notch, BMP

Source:

bioRxiv

Publisher:

Cold Spring Harbor Laboratory Press

Article Number:

174185

Date:

9 August 2017

Official Publication:

https://doi.org/10.1101/174185

Related to:

URL	URL Type
https://edoc.mdc-berlin.de/17080/	Final version

Repository Staff Only: item control page