GSE158957
The Hippo pathway controls myofibril assembly and muscle fiber growth by regulating sarcomeric gene expression
Skeletal muscles are comprised of gigantic multinucleated cells called muscle fibers, which often span several centimetres in length. Each muscle fiber is densely packed with contractile force-producing  myofibrils and ATP-producing mitochondria. During animal development the  size of the individual muscle fibers must dramatically increase to match the growth of the animal and to connect growing skeletal elements. How such dramatic tissue growth is coordinated with growth of the  contractile apparatus in the muscle fibers is not well understood. Here, we use the large Drosophila flight muscles to mechanistically decipher how muscle fiber growth is controlled during development. We isolated flight muscles from Drosophila melanogaster pupae at 24 h and 32 h APF of the genotypes wt, Dlg5-IR, Slmap-IR, Yorkie-CA, Hippo-IR and isolated total RNA for subsequent BRB-seq sequencing. Our study reveals that regulated activity of core members of the Hippo pathway, Hippo, Warts  and Yorkie is required to support post-mitotic flight muscle growth.  Interestingly, we identify Dlg5 and Slmap as important members of the  STRIPAK phosphatase complex, which negatively regulates Hippo activity  and therefore enables post-mitotic muscle growth. Mechanistically, we  find that the Hippo pathway controls the timing and the levels of  sarcomeric gene expression during muscle development and thus regulates  the key components that mediate muscle fiber growth. Since Dlg5, STRIPAK  and the Hippo pathway are conserved in mammals a similar mechanism may  contribute to skeletal muscle or cardiac growth in humans. Overall design: Indirect flight muscle mRNA profiles in Drosophila Melanogaster at two different time points (24h APF and 32h APF) for different conditions (wt, Dlg5-IR, Slmap-IR, Yorkie-CA, Hippo-IR). At least 3 biological replicates per condition are provided.