The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression
- Aix Marseille University, CNRS, IDBM, France
- Max Planck Institute of Biochemistry, Germany
- École Polytechnique Fédérale de Lausanne (EPFL), Switzerland
- Aix Marseille University, CNRS, France
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
Article and author information
Author details
Bianca H Habermann
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
- K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India
Publication history
- Received: October 5, 2020
- Accepted: January 5, 2021
- Accepted Manuscript published: January 6, 2021 (version 1)
- 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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The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression
eLife 10:e63726.
https://doi.org/10.7554/eLife.63726
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