Differential requirements for myogenic regulatory factors distinguish medial and lateral somitic, cranial and fin muscle fibre populations
Differential requirements for myogenic regulatory factors distinguish medial and lateral somitic, cranial and fin muscle fibre populations
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DOI：
10.1242/dev.028019
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发表时间：
2009-02-01
期刊：
影响因子：
4.6
通讯作者：
Hughes, Simon M.
中科院分区：
文献类型：
--
作者：
Hinits, Yaniv;Osborn, Daniel P. S.;Hughes, Simon M.
Myod家族的生肌调节因子是哺乳动物骨骼肌发生所必需的转录因子。然而，每个基因在肌肉发生中的作用尚不清楚，部分原因是Myf5/mrf4基因座上的遗传连锁以及羊膜体节的快速形态发生运动。在小鼠中，Myf5对于最早的外轴肌发生是必不可少的，而Myod是下轴源性肌肉及时分化所必需的。体节的第二个主要细分位于体节本身的原始肌和背轴的体节起源的迁徙肌肉前体之间。在这里，我们使用突变和变形分析相结合的方法来消除斑马鱼中四个保守的MRF基因的每一个功能，斑马鱼是一种保留了更古老的体型的生物。我们发现，体节肌发生的一个基本区别是内侧和外侧间隔，这些间隔既不对应于上/下轴区，也不对应于原始轴/远轴区。在内侧室，Myf5和/或Myod驱动着近轴方向的慢纤维和内侧快纤维的分化。仅肌球蛋白驱动的肌生成素活性就足以从侧脑室形成外侧快速的躯体和胸鳍纤维，以及头盖肌的发生。肌原蛋白的活性对纤维的快速分化起着重要作用。Mrf4对斑马鱼的早期肌肉发生没有贡献。我们认为，在这个新的双组分肌原系统中，复制的MRF类似物的不同使用促进了脊椎动物的多样化。
Myogenic regulatory factors of the Myod family (MRFs) are transcription factors essential for mammalian skeletal myogenesis. However, the roles of each gene in myogenesis remain unclear, owing partly to genetic linkage at the Myf5/Mrf4 locus and to rapid morphogenetic movements in the amniote somite. In mice, Myf5 is essential for the earliest epaxial myogenesis, whereas Myod is required for timely differentiation of hypaxially derived muscle. A second major subdivision of the somite is between primaxial muscle of the somite proper and abaxial somite-derived migratory muscle precursors. Here, we use a combination of mutant and morphant analysis to ablate the function of each of the four conserved MRF genes in zebrafish, an organism that has retained a more ancestral bodyplan. We show that a fundamental distinction in somite myogenesis is into medial versus lateral compartments, which correspond to neither epaxial/hypaxial nor primaxial/abaxial subdivisions. In the medial compartment, Myf5 and/or Myod drive adaxial slow fibre and medial fast fibre differentiation. Myod-driven Myogenin activity alone is sufficient for lateral fast somitic and pectoral fin fibre formation from the lateral compartment, as well as for cranial myogenesis. Myogenin activity is a significant contributor to fast fibre differentiation. Mrf4 does not contribute to early myogenesis in zebrafish. We suggest that the differential use of duplicated MRF paralogues in this novel two-component myogenic system facilitated the diversification of vertebrates.