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.
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.
Metrics
-
- 3,233
- views
-
- 487
- downloads
-
- 37
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
Further reading
-
- Developmental Biology
- Genetics and Genomics
What determines whether an endothelial cell becomes part of an artery, a vein or a capillary?
-
- Developmental Biology
The first cell-fate decision is the process by which cells of an embryo take on distinct lineage identities for the first time, thus representing the beginning of developmental patterning. Here, we demonstrate that the molecular chaperone heat shock protein A2 (HSPA2), a member of the 70 kDa heat shock protein (HSP70) family, is asymmetrically expressed in the late 2-cell stage of mouse embryos. The knockdown of Hspa2 in one of the 2-cell blastomeres prevented its progeny predominantly towards the inner cell mass (ICM) fate. In contrast, the overexpression of Hspa2 in one of the 2-cell blastomeres did not induce the blastomere to differentiate towards the ICM fate. Furthermore, we demonstrated that HSPA2 interacted with CARM1 and its levels correlated with ICM-associated genes. Collectively, our results identify HSPA2 as a critical early regulator of the first cell-fate decision in mammalian 2-cell embryos.
