The Hippo Pathway Controls Myofibril Assembly and Muscle Fiber Growth by Regulating Sarcomeric Gene Expression

Overview

Journal Elife

Specialty Biology

Date 2021 Jan 6

PMID 33404503

Citations 19

Authors

Aynur Kaya-Copur

Fabio Marchiano

Marco Y Hein

Daniel Alpern

Julie Russeil

Nuno Miguel Luis

Matthias Mann

Bart Deplancke

Bianca H Habermann

Frank Schnorrer

Affiliations

Soon will be listed here.

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 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.

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