PUBLICATION

Myogenin is an essential regulator of adult myofibre growth and muscle stem cell homeostasis

Authors
Ganassi, M., Badodi, S., Wanders, K., Zammit, P.S., Hughes, S.M.
ID
ZDB-PUB-201002-227
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Hughes, Simon M.
Keywords
developmental biology, regenerative medicine, stem cells, zebrafish
MeSH Terms
  • Animals
  • Gene Knockout Techniques
  • Homeostasis
  • Muscle, Skeletal/growth & development*
  • Muscle, Skeletal/metabolism
  • Myofibrils/metabolism
  • Myofibrils/physiology*
  • Myogenin/metabolism
  • Myogenin/physiology*
  • Stem Cells/metabolism
  • Stem Cells/physiology*
  • Zebrafish
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
33001028 Full text @ Elife
Abstract
Growth and maintenance of skeletal muscle fibres depend on coordinated activation and return to quiescence of resident muscle stem cells (MuSCs). The transcription factor Myogenin (Myog) regulates myocyte fusion during development, but its role in adult myogenesis remains unclear. In contrast to mice, myog-/- zebrafish are viable, but have hypotrophic muscles. By isolating adult myofibres with associated MuSCs we found that myog-/- myofibres have severely reduced nuclear number, but increased myonuclear domain size. Expression of fusogenic genes is decreased, Pax7 upregulated, MuSCs are fivefold more numerous and mis-positioned throughout the length of myog-/- myofibres instead of localising at myofibre ends as in wild-type. Loss of Myog dysregulates mTORC1 signalling, resulting in an 'alerted' state of MuSCs, which display precocious activation and faster cell cycle entry ex vivo, concomitant with myod upregulation. Thus, beyond controlling myocyte fusion, Myog influences the MuSC:niche relationship, demonstrating a multi-level contribution to muscle homeostasis throughout life.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping