IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_ncomms14582.html
   My bibliography  Save this article

Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth

Author

Listed:
  • Chiara V. Ragni

    (Institut Pasteur
    CNRS URA2578
    Sorbonne Universités, UPMC Université Paris 06, IFD)

  • Nicolas Diguet

    (Institut Pasteur
    CNRS URA2578)

  • Jean-François Le Garrec

    (Institut Pasteur
    CNRS URA2578
    Present address: Imagine-Institut Pasteur, Laboratory of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France)

  • Marta Novotova

    (Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences)

  • Tatiana P. Resende

    (Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto
    Instituto de Engenharia Biomédica (INEB), Universidade do Porto)

  • Sorin Pop

    (Institut Pasteur, Quantitative Image Analysis Unit
    CNRS URA 2582)

  • Nicolas Charon

    (ENS Cachan, Center of Mathematics and Their Applications
    CNRS UMR 8536)

  • Laurent Guillemot

    (Institut Pasteur
    Present address: Imagine-Institut Pasteur, Laboratory of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France)

  • Lisa Kitasato

    (Present address: Imagine-Institut Pasteur, Laboratory of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France)

  • Caroline Badouel

    (Samuel Lunenfeld Research Institute, Mt Sinai Hospital)

  • Alexandre Dufour

    (Institut Pasteur, Quantitative Image Analysis Unit
    CNRS URA 2582)

  • Jean-Christophe Olivo-Marin

    (Institut Pasteur, Quantitative Image Analysis Unit
    CNRS URA 2582)

  • Alain Trouvé

    (ENS Cachan, Center of Mathematics and Their Applications
    CNRS UMR 8536)

  • Helen McNeill

    (Samuel Lunenfeld Research Institute, Mt Sinai Hospital)

  • Sigolène M Meilhac

    (Institut Pasteur
    CNRS URA2578
    Present address: Imagine-Institut Pasteur, Laboratory of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France)

Abstract

Although in flies the atypical cadherin Fat is an upstream regulator of Hippo signalling, the closest mammalian homologue, Fat4, has been shown to regulate tissue polarity rather than growth. Here we show in the mouse heart that Fat4 modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker, with increased cardiomyocyte size and proliferation, and this is mediated by an upregulation of the transcriptional activity of Yap1, an effector of the Hippo pathway. Fat4 is not required for the canonical activation of Hippo kinases but it sequesters a partner of Yap1, Amotl1, out of the nucleus. The nuclear translocation of Amotl1 is accompanied by Yap1 to promote cardiomyocyte proliferation. We, therefore, identify Amotl1, which is not present in flies, as a mammalian intermediate for non-canonical Hippo signalling, downstream of Fat4. This work uncovers a mechanism for the restriction of heart growth at birth, a process which impedes the regenerative potential of the mammalian heart.

Suggested Citation

  • Chiara V. Ragni & Nicolas Diguet & Jean-François Le Garrec & Marta Novotova & Tatiana P. Resende & Sorin Pop & Nicolas Charon & Laurent Guillemot & Lisa Kitasato & Caroline Badouel & Alexandre Dufour , 2017. "Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14582
    DOI: 10.1038/ncomms14582
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms14582
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms14582?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Elliot Medina & Yathreb Easa & Daniel K. Lester & Eric K. Lau & David Sprinzak & Vincent C. Luca, 2023. "Structure of the planar cell polarity cadherins Fat4 and Dachsous1," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Cheng-Hai Zhang & Yao Gao & Han-Hwa Hung & Zhu Zhuo & Alan J. Grodzinsky & Andrew B. Lassar, 2022. "Creb5 coordinates synovial joint formation with the genesis of articular cartilage," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14582. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.