YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development
- Max Delbrück Centre for Molecular Medicine, Germany
- Max Planck Institute for Heart and Lung Research, Germany
- Max Delbrück Center for Molecular Medicine, Germany
- Instituto de Medicina Molecular, Portugal
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.
Article and author information
Author details
Anne-Clémence Vion
Funding
H2020 European Research Council (Consolidator Grant Reshape 311719)
- Holger Gerhardt
H2020 European Research Council (Starting Grant ANGIOMET (311546))
- Michael Potente
Deutsche Forschungsgemeinschaft (SFB 834)
- Michael Potente
Excellence Cluster Cardiopulmonary System (EXC 147/1)
- Michael Potente
LOEWE Research Initiatives Network (Ub-Net)
- Michael Potente
Stiftung Charité
- Michael Potente
European Molecular Biology Organization (Young Investigator Programme)
- Michael Potente
Portugal2020 Program (LISBOA-01-0145-FEDER-00739)
- Claudio A Franco
Fundação para a Ciência e a Tecnologia (SFRH/BD/51287/2010)
- Filipa Neto
European Molecular Biology Organization (Long-Term Fellowship ALTF 1625-2014)
- Anna Szymborska
Deutsches Zentrum für Herz-Kreislaufforschung (REMODEL)
- Alexandra Klaus-Bergmann
- Anne-Clémence Vion
- Eireen Bartels-Klein
- Holger Gerhardt
H2020-TWINN-2015 (ReTuBi-692322)
- Claudio A Franco
Fundação para a Ciência e a Tecnologia (SFRH/BD/52224/2013)
- Joana R Carvalho
Fundação para a Ciência e a Tecnologia (FCT Investigator IF/00412/2012)
- Claudio A Franco
H2020 European Research Council (EC-ERC Starting Grant AXIAL.EC-679368)
- Claudio A Franco
Fundação para a Ciência e a Tecnologia (EXPL/BEX-BCM/2258/2013)
- Claudio A Franco
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures involving handling of living animals were performed in accordance with: the United Kingdom's Home Office Animal Act 1986 under the authority of project licence PPL 80/2391 (experiments done in LRI-CRUK); the German animal protection law with approval by the regional offices for health and social services LaGeSo, under the animal licence IC113 G 0117/15 (experiments done in MDC); institutional guidelines and laws, following protocols approved by local animal ethics committees and authorities (B2/1061; Regierungspraesidium Darmstadt) (experiments done at the MPI for Heart and Lung Research).
Copyright
© 2018, Neto et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development
eLife 7:e31037.
https://doi.org/10.7554/eLife.31037
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