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Myogenin promotes myocyte fusion to balance fibre number and size
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 rol...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185967/ https://www.ncbi.nlm.nih.gov/pubmed/30315160 http://dx.doi.org/10.1038/s41467-018-06583-6 |
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author | Ganassi, Massimo Badodi, Sara Ortuste Quiroga, Huascar Pedro Zammit, Peter S. Hinits, Yaniv Hughes, Simon M. |
author_facet | Ganassi, Massimo Badodi, Sara Ortuste Quiroga, Huascar Pedro Zammit, Peter S. Hinits, Yaniv Hughes, Simon M. |
author_sort | Ganassi, Massimo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6185967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61859672018-10-15 Myogenin promotes myocyte fusion to balance fibre number and size Ganassi, Massimo Badodi, Sara Ortuste Quiroga, Huascar Pedro Zammit, Peter S. Hinits, Yaniv Hughes, Simon M. Nat Commun Article 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. Nature Publishing Group UK 2018-10-12 /pmc/articles/PMC6185967/ /pubmed/30315160 http://dx.doi.org/10.1038/s41467-018-06583-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ganassi, Massimo Badodi, Sara Ortuste Quiroga, Huascar Pedro Zammit, Peter S. Hinits, Yaniv Hughes, Simon M. Myogenin promotes myocyte fusion to balance fibre number and size |
title | Myogenin promotes myocyte fusion to balance fibre number and size |
title_full | Myogenin promotes myocyte fusion to balance fibre number and size |
title_fullStr | Myogenin promotes myocyte fusion to balance fibre number and size |
title_full_unstemmed | Myogenin promotes myocyte fusion to balance fibre number and size |
title_short | Myogenin promotes myocyte fusion to balance fibre number and size |
title_sort | myogenin promotes myocyte fusion to balance fibre number and size |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185967/ https://www.ncbi.nlm.nih.gov/pubmed/30315160 http://dx.doi.org/10.1038/s41467-018-06583-6 |
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