PT  - JOURNAL ARTICLE
AU  - Aynur Kaya-Çopur
AU  - Fabio Marchiano
AU  - Marco Y. Hein
AU  - Daniel Alpern
AU  - Julie Russeil
AU  - Nuno Miguel Luis
AU  - Matthias Mann
AU  - Bart Deplancke
AU  - Bianca H. Habermann
AU  - Frank Schnorrer
TI  - The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression
AID  - 10.1101/2020.10.08.330951
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.08.330951
4099  - http://biorxiv.org/content/early/2020/10/09/2020.10.08.330951.short
4100  - http://biorxiv.org/content/early/2020/10/09/2020.10.08.330951.full
AB  - 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.