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

ABSTRACT: 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE158957 | GEO | 2020/10/03

REPOSITORIES: GEO

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