Myotome adaptability confers developmental robustness to somitic myogenesis in response to fibre number alteration.
Myotome adaptability confers developmental robustness to somitic myogenesis in response to fibre number alteration.
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DOI：
10.1016/j.ydbio.2017.08.029
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发表时间：
2017-11-15
影响因子：
2.7
通讯作者：
Hughes SM
中科院分区：
文献类型：
--
作者：
Roy SD;Williams VC;Pipalia TG;Li K;Hammond CL;Knappe S;Knight RD;Hughes SM
平衡干细胞及其后代的数量对于组织发育和修复至关重要。在这里，我们研究了斑马鱼体细胞肌肉发育过程中细胞数量和整体肌肉大小如何受到严格调节。表达 Pax7 的肌肉干/前体细胞 (MPC) 最初位于真皮肌节 (DM) 外细胞层，采用高度定型分布，此后一部分 MPC 迁移到肌节中。 MPC 增殖和终末分化的区域差异有助于肌节的生长。为了探讨 MPC 肌肉大小控制和时空调节的稳健性，我们将野生型 (wt) MPC 的行为与缺乏肌肉调节因子 Myod 的突变斑马鱼的行为进行了比较。 Myodfh261 突变体形成的多核快肌纤维比野生型少三分之一，并且显示出 DM 中 Pax7+ MPC 群体的显着扩展。随后，myodfh261 突变纤维每个核产生更多的细胞质，导致肌肉体积恢复。此外，相对于wt兄弟姐妹，myodfh261突变体中的MPC数量增加，并且它们过早地迁移到肌组中，分化并导致现有纤维的肥大。因此，过量 MPC 的稳态减少使其数量恢复到正常水平，但纤维数量仍然很低。 GSK3 拮抗剂 BIO 阻止 MPC 迁移到深层肌节，这表明经典 Wnt 通路激活可以维持斑马鱼的 DM，就像羊膜动物一样。然而，BIO 不会阻止 myodfh261 突变体肌组的恢复，这表明体内平衡作用于纤维内在生长以维持肌肉体积。研究结果表明，早期快速纤维形成存在一个关键窗口，随后是一个稳态机制通过控制纤维尺寸来调节肌节生长的时期。我们在肌肉中揭示的反馈控制有助于解释肌节大小沿身体轴的极其精确的分级，而与鱼的大小、营养和遗传变异无关，并且可能形成更广泛匹配器官大小的范例。提出了早期肌纤维形成的关键窗口。缺乏 MyoD1 的鱼形成的肌肉纤维较少，但具有更多的生肌干细胞。在随后的发育过程中，干细胞数量迅速恢复正常。 GSK3 活性促进成肌细胞迁移至肌组，MyoD1 延迟其迁移。补偿性纤维尺寸的增加确保了整体肌肉尺寸的稳健性。
Balancing the number of stem cells and their progeny is crucial for tissue development and repair. Here we examine how cell numbers and overall muscle size are tightly regulated during zebrafish somitic muscle development. Muscle stem/precursor cell (MPCs) expressing Pax7 are initially located in the dermomyotome (DM) external cell layer, adopt a highly stereotypical distribution and thereafter a proportion of MPCs migrate into the myotome. Regional variations in the proliferation and terminal differentiation of MPCs contribute to growth of the myotome. To probe the robustness of muscle size control and spatiotemporal regulation of MPCs, we compared the behaviour of wild type (wt) MPCs with those in mutant zebrafish that lack the muscle regulatory factor Myod. Myodfh261 mutants form one third fewer multinucleate fast muscle fibres than wt and show a significant expansion of the Pax7+ MPC population in the DM. Subsequently, myodfh261 mutant fibres generate more cytoplasm per nucleus, leading to recovery of muscle bulk. In addition, relative to wt siblings, there is an increased number of MPCs in myodfh261 mutants and these migrate prematurely into the myotome, differentiate and contribute to the hypertrophy of existing fibres. Thus, homeostatic reduction of the excess MPCs returns their number to normal levels, but fibre numbers remain low. The GSK3 antagonist BIO prevents MPC migration into the deep myotome, suggesting that canonical Wnt pathway activation maintains the DM in zebrafish, as in amniotes. BIO does not, however, block recovery of the myodfh261 mutant myotome, indicating that homeostasis acts on fibre intrinsic growth to maintain muscle bulk. The findings suggest the existence of a critical window for early fast fibre formation followed by a period in which homeostatic mechanisms regulate myotome growth by controlling fibre size. The feedback controls we reveal in muscle help explain the extremely precise grading of myotome size along the body axis irrespective of fish size, nutrition and genetic variation and may form a paradigm for wider matching of organ size. A critical window for early muscle fibre formation is proposed. Fish lacking MyoD1 form fewer muscle fibres, but have more myogenic stem cells. Stem cell numbers rapidly return to normal during subsequent development. GSK3 activity promotes and MyoD1 delays myoblast migration into the myotome. Compensatory fibre size increase ensures robustness of overall muscle size.
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DOI：
10.1083/jcb.201310035
发表时间：
2014-04-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bentzinger CF;von Maltzahn J;Dumont NA;Stark DA;Wang YX;Nhan K;Frenette J;Cornelison DD;Rudnicki MA
通讯作者：
Rudnicki MA
影响因子：
4.6
作者：
Hinits, Yaniv;Osborn, Daniel P. S.;Hughes, Simon M.
通讯作者：
Hughes, Simon M.
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：
4.2
作者：
Cavalier-Smith, T
通讯作者：
Cavalier-Smith, T
影响因子：
15.9
作者：
Fernández, AM;Dupont, J;Le Roith, D
通讯作者：
Le Roith, D