Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis

Alan Rawls, Julia Hsi Morris, Michael Rudnicki, Thomas Braun, Hans Henning Arnold, William H. Klein, Eric N. Olson

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

The four myogenic basic helix-loop-helix proteins, MyoD, myogenin, Myf-5, and MRF4, can each activate skeletal muscle differentiation when introduced into nonmuscle cells. During embryogenesis, each of these genes is expressed in a unique but overlapping pattern in skeletal muscle precursors and their descendants. Gene knockout experiments have shown that MyoD and Myf-5 play seemingly redundant roles in the generation of myoblasts. However, the role of either of these genes during differentiation in vivo has not been determined. In contrast, a myogenin-null mutation blocks differentiation and results in a dramatic decrease in muscle fiber formation, yet the role of myogenin in the generation or maintenance of myoblast populations is not known. Because myogenin possesses the same myogenic activity as MyoD and Myf-5 in vitro and the expression patterns of these three genes overlap in vivo, we sought to determine if myogenin shares certain functions with either MyoD or Myf-5 in vivo. We therefore generated mice with double homozygous null mutations in the genes encoding MyoD and myogenin or Myf-5 and myogenin. These mice showed embryonic and perinatal phenotypes characteristic of the combined defects observed in mice mutant for each gene alone. As shown by histological analysis and expression of muscle-specific genes, the numbers of undifferentiated myoblasts and residual myofibers were comparable between myogenin-mutant homozygotes and the double-mutant homozygotes. Myoblasts isolated from neonates of the combined mutant genotypes underwent myogenesis in tissue culture, indicating that no more than two of the four myogenic factors are required to support muscle differentiation. These results demonstrate that the functions of myogenin do not overlap with those of MyoD or Myf-5 and support the view that myogenin acts in a genetic pathway downstream of MyoD and Myf-5.

Original languageEnglish (US)
Pages (from-to)37-50
Number of pages14
JournalDevelopmental Biology
Volume172
Issue number1
StatePublished - 1995

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Myogenin
Embryonic Development
Myoblasts
Genes
Homozygote
Muscles
Skeletal Muscle
MyoD Protein
Gene Knockout Techniques
Mutation
Muscle Development
Genotype
Maintenance

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Cell Biology

Cite this

Rawls, A., Morris, J. H., Rudnicki, M., Braun, T., Arnold, H. H., Klein, W. H., & Olson, E. N. (1995). Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis. Developmental Biology, 172(1), 37-50.

Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis. / Rawls, Alan; Morris, Julia Hsi; Rudnicki, Michael; Braun, Thomas; Arnold, Hans Henning; Klein, William H.; Olson, Eric N.

In: Developmental Biology, Vol. 172, No. 1, 1995, p. 37-50.

Research output: Contribution to journalArticle

Rawls, A, Morris, JH, Rudnicki, M, Braun, T, Arnold, HH, Klein, WH & Olson, EN 1995, 'Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis', Developmental Biology, vol. 172, no. 1, pp. 37-50.
Rawls A, Morris JH, Rudnicki M, Braun T, Arnold HH, Klein WH et al. Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis. Developmental Biology. 1995;172(1):37-50.
Rawls, Alan ; Morris, Julia Hsi ; Rudnicki, Michael ; Braun, Thomas ; Arnold, Hans Henning ; Klein, William H. ; Olson, Eric N. / Myogenin's functions do not overlap with those of MyoD or Myf-5 during mouse embryogenesis. In: Developmental Biology. 1995 ; Vol. 172, No. 1. pp. 37-50.
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