Key result
Loss of Myogenin in adult zebrafish resulted in hypotrophic muscle with severely reduced nuclear number, increased myonuclear domain size, and a fivefold increase in mis-positioned muscle stem cells.
Why the study?
The transcription factor Myogenin regulates myocyte fusion during development, but its role in adult myogenesis remains unclear.
Myogenin plays a crucial role in adult skeletal muscle homeostasis by regulating the muscle stem cell niche and preventing precocious activation, extending its known role beyond developmental myocyte fusion.
Answers are grounded in this paper and cite their sources.
Myog loss reduces adult zebrafish myofiber nuclear number; leaves open its role in mammalian MuSC maintenance.
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 −/− myofibers 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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Ganassi et al. (2020) studied Myogenin deficiency. myog-/- mutation vs. myog+/- heterozygous siblings was evaluated. Loss of Myogenin in adult zebrafish resulted in hypotrophic muscle with severely reduced nuclear number, increased myonuclear domain size, and a fivefold increase in mis-positioned muscle stem cells.
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