1. Developmental Biology
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The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression

  1. Aynur Kaya-Çopur  Is a corresponding author
  2. Fabio Marchiano
  3. Marco Y Hein
  4. Daniel Alpern
  5. Julie Russeil
  6. Nuno Miguel Luis
  7. Matthias Mann
  8. Bart Deplancke
  9. Bianca H Habermann
  10. Frank Schnorrer  Is a corresponding author
  1. Aix Marseille University, CNRS, IDBM, France
  2. Max Planck Institute of Biochemistry, Germany
  3. École Polytechnique Fédérale de Lausanne (EPFL), Switzerland
  4. Aix Marseille University, CNRS, France
Research Article
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Cite this article as: eLife 2021;10:e63726 doi: 10.7554/eLife.63726

Abstract

Skeletal muscles are composed of gigantic cells called muscle fibers, packed with force-producing myofibrils. During development the size of individual muscle fibers must dramatically enlarge to match with skeletal growth. How muscle growth is coordinated with growth of the contractile apparatus is not understood. Here, we use the large Drosophila flight muscles to mechanistically decipher how muscle fiber growth is controlled. We find that regulated activity of core members of the Hippo pathway is required to support flight muscle growth. Interestingly, we identify Dlg5 and Slmap as regulators of the STRIPAK phosphatase, which negatively regulates Hippo to enable post-mitotic muscle growth. Mechanistically, we show that the Hippo pathway controls timing and levels of sarcomeric gene expression during development and thus regulates the key components that physically mediate muscle growth. Since Dlg5, STRIPAK and the Hippo pathway are conserved a similar mechanism may contribute to muscle or cardiomyocyte growth in humans.

Data availability

Sequencing data have been deposited in GEO under accession code GSE158957

The following data sets were generated

Article and author information

Author details

  1. Aynur Kaya-Çopur

    Muscle Dynamics, Aix Marseille University, CNRS, IDBM, Marseille, France
    For correspondence
    aynur.KAYA-COPUR@univ-amu.fr
    Competing interests
    The authors declare that no competing interests exist.
  2. Fabio Marchiano

    Computational Biology, Aix Marseille University, CNRS, IDBM, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Marco Y Hein

    Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9490-2261
  4. Daniel Alpern

    Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Julie Russeil

    Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Nuno Miguel Luis

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5438-9638
  7. Matthias Mann

    Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1292-4799
  8. Bart Deplancke

    School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9935-843X
  9. Bianca H Habermann

    Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2457-7504
  10. Frank Schnorrer

    Muscle Dynamics, Aix Marseille University, CNRS, IDBM, Marseille, France
    For correspondence
    frank.schnorrer@univ-amu.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9518-7263

Funding

European Research Council ERC (FP/2007-2013)

  • Frank Schnorrer

Bettencourt Foundation

  • Frank Schnorrer

Turing Center for Living Systems

  • Frank Schnorrer

Max Planck Society

  • Frank Schnorrer

Centre National de la Recherche Scientifique

  • Frank Schnorrer

Aix-Marseille Université (ANR-11-IDEX-0001-02)

  • Frank Schnorrer

Agence Nationale de la Recherche (ANR-ACHN MUSCLE-FORCES)

  • Frank Schnorrer

Agence Nationale de la Recherche (ANR-18-CE45-0016-01)

  • Bianca H Habermann

Human Frontier Science Program (RGP0052/2018)

  • Frank Schnorrer

Agence Nationale de la Recherche (ANR-10-INBS-04-01)

  • Frank Schnorrer

Humboldt Foundation

  • Aynur Kaya-Çopur

EMBO

  • Aynur Kaya-Çopur

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Publication history

  1. Received: October 5, 2020
  2. Accepted: January 5, 2021
  3. Accepted Manuscript published: January 6, 2021 (version 1)
  4. Version of Record published: January 18, 2021 (version 2)

Copyright

© 2021, Kaya-Çopur 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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