Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; Vascular Biology Laboratory, Lincoln’s Inn Fields Laboratories, London Research Institute – Cancer Research UK, London, United Kingdom
Alexandra Klaus-Bergmann
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; DZHK (German Center for Cardiovascular Research), Berlin, Germany
Vascular Morphogenesis Laboratory, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
Michael Potente
DZHK (German Center for Cardiovascular Research), Berlin, Germany; Angiogenesis and Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; International Institute of Molecular and Cell Biology, Warsaw, Poland
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; Vascular Biology Laboratory, Lincoln’s Inn Fields Laboratories, London Research Institute – Cancer Research UK, London, United Kingdom; DZHK (German Center for Cardiovascular Research), Berlin, Germany; Vascular Patterning Laboratory, Vesalius Research Center, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium; Berlin Institute of Health, Berlin, Germany
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.
