1. Cell Biology
  2. Developmental Biology

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

  1. Filipa Neto
  2. Alexandra Klaus-Bergmann
  3. Yu Ting Ong
  4. Silvanus Alt
  5. Anne-Clémence Vion
  6. Anna Szymborska
  7. Joana R Carvalho
  8. Irene Hollfinger
  9. Eireen Bartels-Klein
  10. Claudio A Franco
  11. Michael Potente  Is a corresponding author
  12. Holger Gerhardt  Is a corresponding author
  1. Max Delbrück Centre for Molecular Medicine, Germany
  2. Max Planck Institute for Heart and Lung Research, Germany
  3. Max Delbrück Center for Molecular Medicine, Germany
  4. Instituto de Medicina Molecular, Portugal
https://doi.org/10.7554/eLife.31037
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  1. Filipa Neto
  2. Alexandra Klaus-Bergmann
  3. Yu Ting Ong
  4. Silvanus Alt
  5. Anne-Clémence Vion
  6. Anna Szymborska
  7. Joana R Carvalho
  8. Irene Hollfinger
  9. Eireen Bartels-Klein
  10. Claudio A Franco
  11. Michael Potente
  12. Holger Gerhardt
(2018)
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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  3. Download .RIS

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

  1. Filipa Neto

    Integrative Vascular Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    No competing interests declared.

  2. Alexandra Klaus-Bergmann

    Integrative Vascular Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    No competing interests declared.

  3. Yu Ting Ong

    Angiogenesis and Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3407-2515

  4. Silvanus Alt

    Integrative Vascular Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    No competing interests declared.

  5. Anne-Clémence Vion

    Vascular Biology Laboratory, Max Delbrück Center for Molecular Medicine, Berlin, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2788-2512

  6. Anna Szymborska

    Integrative Vascular Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    No competing interests declared.

  7. Joana R Carvalho

    Vascular Morphogenesis Laboratory, Instituto de Medicina Molecular, Lisbon, Portugal
    Competing interests
    No competing interests declared.

  8. Irene Hollfinger

    Integrative Vascular Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    No competing interests declared.

  9. Eireen Bartels-Klein

    Integrative Vascular Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
    Competing interests
    No competing interests declared.

  10. Claudio A Franco

    Vascular Morphogenesis Laboratory, Instituto de Medicina Molecular, Lisbon, Portugal
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2861-3883

  11. Michael Potente

    Angiogenesis and Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    For correspondence
    michael.potente@mpi-bn.mpg.de
    Competing interests
    No competing interests declared.

  12. Holger Gerhardt

    Integrative Vascular Biology, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
    For correspondence
    holger.gerhardt@mdc-berlin.de
    Competing interests
    Holger Gerhardt, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3030-0384

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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  1. Filipa Neto
  2. Alexandra Klaus-Bergmann
  3. Yu Ting Ong
  4. Silvanus Alt
  5. Anne-Clémence Vion
  6. Anna Szymborska
  7. Joana R Carvalho
  8. Irene Hollfinger
  9. Eireen Bartels-Klein
  10. Claudio A Franco
  11. Michael Potente
  12. Holger Gerhardt
(2018)
YAP and TAZ regulate adherens junction dynamics and endothelial cell distribution during vascular development
eLife 7:e31037.
https://doi.org/10.7554/eLife.31037

Share this article

https://doi.org/10.7554/eLife.31037

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