Journal
ELIFE
Volume 10, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.63726
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Funding
- European Research Council [FP/2007-2013]
- Centre National de la Recherche Scientifique
- Aix-Marseille Universite [ANR-11-IDEX-0001-02]
- Agence Nationale de la Recherche [ANR-18-CE45-0016-01, ANR-10-INBS-04-01]
- Human Frontier Science Program [RGP0052/2018]
- Humboldt Foundation
- EMBO
- Fondation Bettencourt Schueller
- Turing Center for Living Sys-tems
- Max Planck Society
- Agence Nationale de la Recherche (ANR) [ANR-18-CE45-0016] Funding Source: Agence Nationale de la Recherche (ANR)
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Research has shown that the regulated activity of core members of the Hippo pathway is necessary for muscle growth, with Dlg5 and Slmap identified as regulators of the STRIPAK phosphatase to enable post-mitotic muscle growth. This pathway controls the timing and levels of sarcomeric gene expression during development, potentially contributing to muscle or cardiomyocyte growth in humans.
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.
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