PT  - JOURNAL ARTICLE
AU  - Filipa Neto
AU  - Alexandra Klaus-Bergmann
AU  - Yu-Ting Ong
AU  - Silvanus Alt
AU  - Anne-Clémence Vion
AU  - Anna Szymborska
AU  - Joana R. Carvalho
AU  - Irene Hollfinger
AU  - Eireen Bartels-Klein
AU  - Claudio A. Franco
AU  - Michael Potente
AU  - Holger Gerhardt
TI  - YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development
AID  - 10.1101/174185
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 174185
4099  - http://biorxiv.org/content/early/2017/08/09/174185.short
4100  - http://biorxiv.org/content/early/2017/08/09/174185.full
AB  - 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.