Differential requirements for myogenic regulatory factors distinguish medial and lateral somitic, cranial and fin muscle fibre populations

Hinits, Y., Osborn, D.P., and Hughes, S.M.
Development (Cambridge, England)   136(3): 403-414 (Journal)
Registered Authors
Hinits, Yaniv, Hughes, Simon M., Osborn, Dan
Muscle, Zebrafish, Myosin, Slow, Fibre, Fast, Head, Fin, mrf4 (myf6), myod, myf5, Myogenin, Hedgehog, prdm1, pax3, meox1, hsp90, mef2d
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/physiology
  • Extremities/embryology
  • Extremities/growth & development
  • Extremities/physiology*
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism
  • Larva
  • Muscle Development/physiology*
  • Muscle Fibers, Skeletal/physiology*
  • Mutation
  • MyoD Protein/genetics
  • MyoD Protein/metabolism
  • Myogenic Regulatory Factor 5/genetics
  • Myogenic Regulatory Factor 5/metabolism
  • Myogenic Regulatory Factors/genetics
  • Myogenic Regulatory Factors/metabolism
  • Myogenin/genetics
  • Myogenin/metabolism
  • Organ Specificity
  • Somites/embryology
  • Somites/physiology*
  • Zebrafish/embryology
  • Zebrafish/growth & development
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
19141670 Full text @ Development
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.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes