Myogenin promotes myocyte fusion to balance fibre number and size

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Abstract

Each skeletal muscle acquires its unique size before birth, when terminally differentiating myocytes fuse to form a defined number of multinucleated myofibres. Although mice in which the transcription factor Myogenin is mutated lack most myogenesis and die perinatally, a specific cell biological role for Myogenin has remained elusive. We report that loss of function of zebrafish myog prevents formation of almost all multinucleated muscle fibres. A second, Myog-independent, fusion pathway requires Hedgehog signalling. Lack of Myog does not prevent terminal differentiation; the smaller myotome has a normal number of myocytes forming more mononuclear, thin, albeit functional, fast muscle fibres. Mechanistically, Myogenin binds the myomaker promoter and is required for expression of myomaker and other genes essential for myocyte fusion. Adult myog mutants display reduced muscle mass, decreased fibre size and nucleation. Adult-derived myog mutant myocytes show persistent defective fusion ex vivo. Myogenin is therefore essential for muscle homeostasis, regulating myocyte fusion to determine both muscle fibre number and size.
Original languageEnglish
Article number4232
Pages (from-to)1-17
JournalNature Communications
Volume9
Early online date12 Oct 2018
DOIs
Publication statusPublished - 12 Oct 2018

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