RRC ID 5612
Author Hinits Y, Hughes SM.
Title Mef2s are required for thick filament formation in nascent muscle fibres.
Journal Development
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.
Volume 134(13)
Pages 2511-9
Published 2007-7
DOI 10.1242/dev.007088
PII dev.007088
PMID 17537787
PMC PMC3016612
MeSH Animals Base Sequence Embryo, Nonmammalian / embryology Embryo, Nonmammalian / metabolism Gene Expression Regulation, Developmental* Heart / embryology Molecular Sequence Data Muscle Fibers, Skeletal / metabolism* Mutation / genetics Myocardium / metabolism Myogenic Regulatory Factors / genetics Myogenic Regulatory Factors / metabolism* Sequence Alignment Sequence Homology, Nucleic Acid Transcription, Genetic / genetics Zebrafish / embryology Zebrafish / genetics Zebrafish / metabolism Zebrafish Proteins / deficiency Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 5.763
Times Cited 73
Zebrafish Tg(alpha-actin:GFP)