The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression

• Published in: eLife Vol. 10
• Main Authors: Kaya-Çopur, Aynur, Marchiano, Fabio, Hein, Marco Y, Alpern, Daniel, Russeil, Julie, Luis, Nuno Miguel, Mann, Matthias, Deplancke, Bart, Habermann, Bianca H, Schnorrer, Frank
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 06.01.2021; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: Animals; Cardiomyocytes; Cell growth; Development Biology; Developmental Biology; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Flight muscle; Gene expression; Gene Expression Regulation; Hippo; Hippo Signaling Pathway - physiology; Insects; Kinases; Life Sciences; Localization; Mammals; Morphogenesis; muscle; Muscle contraction; Muscle Fibers, Skeletal - physiology; myofibril; Myofibrils; Myofibrils - metabolism; Phosphatase; Phosphorylation; Proteins; sarcomere; Sarcomeres - genetics; Skeletal muscle; yorkie; myofibril; Drosophila; Hippo; developmental biology; muscle; yorkie; D. melanogaster; sarcomere
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.63726

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 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.