Myogenin promotes myocyte fusion to balance fibre number and size.
Myogenin promotes myocyte fusion to balance fibre number and size.
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DOI：
10.1038/s41467-018-06583-6
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发表时间：
2018-10-12
影响因子：
16.6
通讯作者：
Hughes SM
中科院分区：
文献类型：
--
作者：
Ganassi M;Badodi S;Ortuste Quiroga HP;Zammit PS;Hinits Y;Hughes SM
每个骨骼肌在出生前获得其独特的大小，当最终分化的肌细胞融合形成一定数量的多核肌纤维时。虽然转录因子Myogenin突变的小鼠缺乏大多数肌肉发生并在围产期死亡，但Myogenin的特定细胞生物学作用仍然难以捉摸。在这里，我们报道斑马鱼肌功能的丧失阻止了几乎所有多核肌纤维的形成。第二种不依赖于肌原蛋白的深肌瘤融合通路需要Hedgehog信号传导。肌原蛋白的缺乏并不妨碍终末分化；较小的肌瘤有正常数量的肌细胞，形成更多的单核、薄但有功能的快速肌纤维。从机制上讲，Myogenin与myomaker启动子结合，是myomaker和其他肌细胞融合所必需的基因表达所必需的。成年肌突变体表现为肌肉量减少，纤维大小和成核减少。成人来源的肌突变细胞在体外表现出持续的有缺陷的融合。因此，肌原素对肌肉稳态至关重要，调节肌细胞融合以决定肌纤维的数量和大小。小鼠中转录因子Myogenin的缺失可减少骨骼肌的发生并导致围产期死亡，但Myogenin如何调节肌肉形成尚不清楚。在这里，作者表明，斑马鱼肌原素增强Myomaker表达，肌肉细胞融合和肌组大小，但减少快速肌纤维数量。
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. Loss of the transcription factor Myogenin in mice reduces skeletal myogenesis and leads to perinatal death but how Myogenin regulates muscle formation is unclear. Here, the authors show that zebrafish Myogenin enhances Myomaker expression, muscle cell fusion and myotome size, yet decreases fast muscle fibre number.
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影响因子：
7.8
作者：
Cusella-De Angelis, M G;Lyons, G;Sonnino, C;De Angelis, L;Vivarelli, E;Farmer, K;Wright, W E;Molinaro, M;Bouche, M;Buckingham, M
通讯作者：
Buckingham, M
DOI：
10.1016/s1096-4959(02)00194-x
发表时间：
2003-01-01
影响因子：
2.2
作者：
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通讯作者：
Anyangwe, V
影响因子：
4.6
作者：
Fin L;Bergamin G;Steiner RA;Hughes SM
通讯作者：
Hughes SM
影响因子：
56.9
作者：
Gurevich, David B.;Phong Dang Nguyen;Currie, Peter D.
通讯作者：
Currie, Peter D.
影响因子：
2.7
作者：
Aday AW;Zhu LJ;Lakshmanan A;Wang J;Lawson ND
通讯作者：
Lawson ND