PUBLICATION

Myogenin promotes myocyte fusion to balance fibre number and size

Authors
Ganassi, M., Badodi, S., Ortuste Quiroga, H.P., Zammit, P.S., Hinits, Y., Hughes, S.M.
ID
ZDB-PUB-181014-2
Date
2018
Source
Nature communications   9: 4232 (Journal)
Registered Authors
Hinits, Yaniv, Hughes, Simon M.
Keywords
none
MeSH Terms
  • Animals
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Female
  • Male
  • Muscle Cells/cytology
  • Muscle Cells/metabolism
  • Myogenin/metabolism
  • NADH Tetrazolium Reductase/metabolism
  • RNA, Messenger/metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish/metabolism*
PubMed
30315160 Full text @ Nat. Commun.
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. Here we report that loss of function of zebrafish myog prevents formation of almost all multinucleated muscle fibres. A second, Myogenin-independent, fusion pathway in the deep myotome requires Hedgehog signalling. Lack of Myogenin 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 to 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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping