Brennan Caroline, Mangoli Maryam, Dyer Clare E F, Ashworth Rachel
School of Biological Sciences, Queen Mary, University of London, London, E1 4NS, UK.
J Cell Sci. 2005 Nov 15;118(Pt 22):5181-90. doi: 10.1242/jcs.02625. Epub 2005 Oct 25.
Nerve activity is known to be an important regulator of muscle phenotype in the adult, but its contribution to muscle development during embryogenesis remains unresolved. We used the zebrafish embryo and in vivo imaging approaches to address the role of activity-generated signals, acetylcholine and intracellular calcium, in vertebrate slow muscle development. We show that acetylcholine drives initial muscle contraction and embryonic movement via release of intracellular calcium from ryanodine receptors. Inhibition of this activity-dependent pathway at the level of the acetylcholine receptor or ryanodine receptor did not disrupt slow fibre number, elongation or migration but affected myofibril organisation. In mutants lacking functional acetylcholine receptors myofibre length increased and sarcomere length decreased significantly. We propose that calcium is acting via the cytoskeleton to regulate myofibril organisation. Within a myofibre, sarcomere length and number are the key parameters regulating force generation; hence our findings imply a critical role for nerve-mediated calcium signals in the formation of physiologically functional muscle units during development.
已知神经活动是成年期肌肉表型的重要调节因子，但其在胚胎发育过程中对肌肉发育的贡献仍未得到解决。我们利用斑马鱼胚胎和体内成像方法，来研究活性产生的信号、乙酰胆碱和细胞内钙在脊椎动物慢肌发育中的作用。我们发现，乙酰胆碱通过从兰尼碱受体释放细胞内钙来驱动初始肌肉收缩和胚胎运动。在乙酰胆碱受体或兰尼碱受体水平抑制这种活性依赖途径，不会破坏慢肌纤维数量、伸长或迁移，但会影响肌原纤维组织。在缺乏功能性乙酰胆碱受体的突变体中，肌纤维长度增加，肌节长度显著缩短。我们认为钙是通过细胞骨架来调节肌原纤维组织的。在肌纤维内，肌节长度和数量是调节力量产生的关键参数；因此，我们的研究结果表明，神经介导钙信号在发育过程中形成生理功能肌肉单位方面起着关键作用。
