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

Filipa Neto, Alexandra Klaus-Bergmann, Yu Ting Ong, Silvanus Alt, Anne Clémence Vion, Anna Szymborska, Joana R. Carvalho, Irene Hollfinger, Eireen Bartels-Klein, Claudio A. Franco, Michael Potente, Holger Gerhardt*

*Autor correspondente para este trabalho

Resultado de pesquisarevisão de pares

159 Citações (Scopus)

Resumo

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 both cell migration and barrier function maintenance. 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.
Idioma originalEnglish
Número do artigoe31037
RevistaeLife
Volume7
DOIs
Estado da publicaçãoPublicado - 5 fev. 2018
Publicado externamenteSim

Impressão digital

Mergulhe nos tópicos de investigação de “YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development“. Em conjunto formam uma impressão digital única.

Citação