Mef2s are required for thick filament formation in nascent muscle fibres
Mef2s are required for thick filament formation in nascent muscle fibres
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DOI：
10.1242/dev.007088
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发表时间：
2007-07-01
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;Hughes, Simon M.
在骨骼肌分化过程中，肌动球蛋白马达被组装成肌原纤维，即产生力并将力传递到细胞末端的多蛋白机器。肌肉蛋白的表达如何协调以构建肌原纤维尚不清楚。在这里，我们表明，斑马鱼 Mef2d 和 Mef2c 蛋白对于新生肌纤维中含有肌球蛋白的粗丝的组装是多余的，但对于骨骼肌纤维分化、伸长、融合或细丝基因表达的早期步骤来说不是必需的。 mef2d mRNA 和蛋白质存在于成肌细胞中，而 mef2c 表达始于肌纤维中。用反义吗啉寡核苷酸或突变鱼敲低 Mef2 会阻断肌肉功能并阻止肌节组装。细胞移植和热休克驱动的救援揭示了纤维内对 Mef2 的细胞自主需求。在新生纤维中，Mef2 驱动编码粗丝蛋白而非细丝蛋白的基因表达。在分析的基因中，肌球蛋白重链、轻链以及肌球蛋白结合蛋白 C 需要 Mef2 才能正常表达，而肌动蛋白、原肌球蛋白和肌钙蛋白则不需要。我们的研究结果表明，Mef2 控制终末分化后的骨骼肌形成，并定义了脊椎动物骨骼肌发育中控制粗丝基因表达的新成熟步骤。
During skeletal muscle differentiation, the actomyosin motor is assembled into myofibrils, multiprotein machines that generate and transmit force to cell ends. How expression of muscle proteins is coordinated to build the myofibril is unknown. Here we show that zebrafish Mef2d and Mef2c proteins are required redundantly for assembly of myosin-containing thick filaments in nascent muscle fibres, but not for the earlier steps of skeletal muscle fibre differentiation, elongation, fusion or thin filament gene expression. mef2d mRNA and protein is present in myoblasts, whereas mef2c expression commences in muscle fibres. Knockdown of both Mef2s with antisense morpholino oligonucleotides or in mutant fish blocks muscle function and prevents sarcomere assembly. Cell transplantation and heat-shock-driven rescue reveal a cell-autonomous requirement for Mef2 within fibres. In nascent fibres, Mef2 drives expression of genes encoding thick, but not thin, filament proteins. Among genes analysed, myosin heavy and light chains and myosin-binding protein C require Mef2 for normal expression, whereas actin, tropomyosin and troponin do not. Our findings show that Mef2 controls skeletal muscle formation after terminal differentiation and define a new maturation step in vertebrate skeletal muscle development at which thick filament gene expression is controlled.