Affiliation:
1. MRC Centre for Developmental Neurobiology and Randall Division for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, UK.
Abstract
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.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference61 articles.
1. Baker, P. W., Tanaka, K. K., Klitgord, N. and Cripps, R. M.(2005). Adult myogenesis in Drosophila melanogaster can proceed independently of myocyte enhancer factor-2. Genetics170,1747-1759.
2. Balza, R. O., Jr and Misra, R. P. (2006). Role of the serum response factor in regulating contractile apparatus gene expression and sarcomeric integrity in cardiomyocytes. J. Biol. Chem.281,6498-6510.
3. Barral, J. M., Hutagalung, A. H., Brinker, A., Hartl, F. U. and Epstein, H. F. (2002). Role of the myosin assembly protein UNC-45 as a molecular chaperone for myosin. Science295,669-671.
4. Barresi, M. J., Stickney, H. L. and Devoto, S. H.(2000). The zebrafish slowmuscle-omitted gene product is required for Hedgehog signal transduction and the development of slow muscle identity. Development127,2189-2199.
5. Baxendale, S., Davison, C., Muxworthy, C., Wolff, C., Ingham, P. W. and Roy, S. (2004). The B-cell maturation factor Blimp-1 specifies vertebrate slow-twitch muscle fiber identity in response to Hedgehog signaling. Nat. Genet.36, 88-93.
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