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
-
- Cells, Cultured
- NADH Tetrazolium Reductase/metabolism
- Female
- Myogenin/metabolism
- RNA, Messenger/metabolism*
- Animals
- Muscle Cells/cytology
- Muscle Cells/metabolism
- Chromatin Immunoprecipitation
- Zebrafish/metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Male
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism
- PubMed
- 30315160 Full text @ Nat. Commun.
Citation
Ganassi, M., Badodi, S., Ortuste Quiroga, H.P., Zammit, P.S., Hinits, Y., Hughes, S.M. (2018) Myogenin promotes myocyte fusion to balance fibre number and size. Nature communications. 9:4232.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping