ZFIN ID: ZDB-PUB-201002-227
Myogenin is an essential regulator of adult myofibre growth and muscle stem cell homeostasis
Ganassi, M., Badodi, S., Wanders, K., Zammit, P.S., Hughes, S.M.
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
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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.
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