Skip to main content
Cellular and Molecular Neurobiology logoLink to Cellular and Molecular Neurobiology
. 1992 Dec;12(6):511–527. doi: 10.1007/BF00711232

Response of myogenic determination factors to cessation and resumption of electrical activity in skeletal muscle: A possible role for myogenin in denervation supersensitivity

Craig M Neville 1, Marlies Schmidt 1, Jakob Schmidt 1,
PMCID: PMC11567343  PMID: 1337017

Abstract

  1. We have prepared probes specific for the chicken myogenic determination genes MyoD, myogenin, myf5, and herculin and have investigated the expression of these genes in response to denervation and acute electrical stimulation in neonate chick muscle, using ribonuclease protection.

  2. Upon denervation, herculin mRNA remains essentially unchanged, myf5 transcript levels approximately double, and MyoD message is up-regulated by two- to fivefold. In contrast, the message coding for myogenin, barely detectable in innervated muscle, rises dramatically (~200-fold) on the second day after nerve section; in this respect it resembles acetylcholine receptor (AChR)α-,γ-andδ-subunit mRNAs. Cohybridization experiments reveal that the increase in myogenin mRNA slightly precedes the rise in AChRα-subunit message.

  3. Electrical stimulation of denervated muscle leads to an immediate decline in myogenin and AChRα-subunit mRNAs, with half-lives of less than an hour and approximately 4 hr, respectively; message stability measurements suggest that this is effected through a rapid shutdown of transcription. Messages coding for MyoD, myf5, and herculin decay much more slowly, as a result of slower turnover.

  4. Previous experiments have indicated the involvement of ade novo induced (Tsay, H.-J., Neville, C. M., and Schmidt, J.,FEBS Lett. 274:69–72, 1990) autocatalytic (Neville, C. M., Schmidt, M., and Schmidt, J.,NeuroReport 2:655–657, 1991) transcription factor in the denervation-triggered up-regulation of AChRα-subunit expression; the denervation and electrical stimulation experiments reported here are compatible with the notion that myogenin is that factor.

Key words: denervation, membrane activity, acetylcholine receptor, α subunit, gene regulation, myogenin

References

  1. Blackwell, T. K., and Weintraub, H. (1990). Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection.Science2501104–1110. [DOI] [PubMed] [Google Scholar]
  2. Braun, T., Buschhausen-Denker, G., Bober, E., Tannich, E., and Arnold, H. (1989). A novel human muscle factor related to but distinct from MyoD1 induces myogenic conversion in 10T1/2 fibroblasts.EMBO J.8701–709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Braun, T., Bober, E., Winter, B., Rosenthal, N., and Arnold, H. (1990). Myf-6, a new member of the human gene family of myogenic determination factors: Evidence for a gene cluster on chromosome 12.EMBO J.9821–831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brennan, T. J., Edmondson, D. G., and Olson, E. N. (1990). Aberrant regulation of MyoD1 contributes to the partially defective phenotype of BC3H-1 cells.J. Cell Biol.110929–937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brunetti, A., and Goldfine, I. D. (1990). Role of myogenin in myoblast differentiation and its regulation by fibroblast growth factor.J. Biol. Chem.2655960–5963. [PubMed] [Google Scholar]
  6. Buskin, J. N., and Hauschka, S. D. (1989). Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene.Mol. Cell. Biol.92627–2640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chirgwin, J. J., Przybyla, A. E., MacDonald, R. J., and Rutter, W. J. (1979). Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.Biochemistry185294–5300. [DOI] [PubMed] [Google Scholar]
  8. Donoghue, M., Ernst, H., Wentworth, B., Nadal-Ginard, B., and Rosenthal, N. (1988). A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus.Genes Dev.21779–1790. [DOI] [PubMed] [Google Scholar]
  9. Duclert, A., Piette, J., and Changeux, J. P. (1991). Influence of innervation on myogenic factors and acetylcholine receptorα-subunit mRNAs.NeuroReport225–28. [DOI] [PubMed] [Google Scholar]
  10. Eftimie, R., Brenner, H. R., and Buonanno, A. (1991). Myogenin and MyoD join a family of skeletal muscle genes regulated by electrical activity.Proc. Natl. Acad. Sci. USA881349–1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fujisawa-Sehara, A., Nabeshima, Y., Hosoda, Y., and Obinata, T. (1990). Myogenin contains two domains conserved among myogenic factors.J. Biol. Chem.26515219–15223. [PubMed] [Google Scholar]
  12. Goldman, D., Brenner, H. R., and Heinemann, S. (1988). Acetylcholine receptorα-,β-,γ-, andδ-subunit mRNA levels are regulated by muscle activity.Neuron1329–333. [DOI] [PubMed] [Google Scholar]
  13. Hall, Z. E., and Reinness, C. G. (1977). Electrical stimulation of denervated muscles reduces incorporation of methionine into acetylcholine receptor.Nature268655–657. [DOI] [PubMed] [Google Scholar]
  14. Jia, H.-T., Tsay, H.-J., and Schmidt, J. (1992). Analysis of binding and activating functions of the chick muscle acetylcholine receptorγ subunit upstream sequence.Cell. Mol. Neurobiol.12241–258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klarsfeld, A., Laufer, R., Fontaine, B., Devillers-Thiery, A., Dubreuil, C., and Changeux, J.-P. (1989). Regulation of muscle AChRα subunit gene expression by electrical activity: Involvement of protein kinase C and Ca2+.Neuron21229–1236. [DOI] [PubMed] [Google Scholar]
  16. Lassar, A. B., Buskin, J. N., Lockshon, D., Davis, R. L., Apone, S., Hauschka, S. D., and Weintraub, H. (1989). MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer.Cell58823–831. [DOI] [PubMed] [Google Scholar]
  17. Lin, Z. Y., Dechesne, C. A., Eldridge, J., and Paterson, B. M. (1989). An avian muscle factor related to MyoD1 activates muscle-specific promoters in nonmuscle cells of different germ-layer origin and in BrdU-treated myoblasts.Genes Dev.3986–996. [DOI] [PubMed] [Google Scholar]
  18. Lømo, T., and Westgaard, R. H. (1975). Further studies on the control of ACh sensitivity by muscle activity in the rat.J. Physiol. (London)252603–626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Melton, D. A., Krieg, P. A., Rebagliati, M., Maniatis, T., Zinn, K., and Green, M. R. (1984). Efficientin vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.Nucl. Acids Res.127035–7056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Merlie, J. P., and Kornhauser, J. M. (1989). Neural regulation of gene expression by an acetylcholine receptor promoter in muscle of transgenic mice.Neuron21295–1300. [DOI] [PubMed] [Google Scholar]
  21. Merlie, J. P., McKinnon, D., and Sanes, J. R. (1991). Transgenic analysis of acetylcholine receptor gene expression.J. Cell. Biochem.15C12. [Google Scholar]
  22. Miner, J. H., and Wold, B. (1990). Herculin, a fourth member of theMyoD family of myogenic regulatory genes.Proc. Natl. Acad. Sci. USA871089–1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Moss, S. J., Beeson, D. M. W., Jackson, J. F., Darlison, M. G., and Barnard, E. A. (1987). Differential expression of nicotinic acetylcholine receptor genes in innervated and denervated chicken muscle.EMBO J.63917–3921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Murre, C., McCaw, P. S., Vaessin, H., Caudy, M., Jan, Y. N., Cabrera, C. V., Buskin, J. N., Hauschka, S. D., and Lassar, A. B. (1989). Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.Cell58537–544. [DOI] [PubMed] [Google Scholar]
  25. Neville, C. M., Schmidt, M., and Schmidt, J. (1991). Kinetics of expression of acetylcholine receptorα-subunit mRNA in denervated and stimulated muscle.NeuroReport2655–657. [DOI] [PubMed] [Google Scholar]
  26. Olson, E. N. (1990). MyoD family: A paradigm for development?Genes Dev.41454–1461. [DOI] [PubMed] [Google Scholar]
  27. Piette, J., Bessereau, J.-L., Huchet, M., and Changeux, J.-P. (1990). Two adjacent MyoD1-binding sites regulate expression of the acetylcholine receptorα-subunit gene.Nature345353–355. [DOI] [PubMed] [Google Scholar]
  28. Richter, E. A., Cleland, P. J. F., Rattigan, S., and Clark, M. G. (1987). Contraction-associated translocation of protein kinase C in rat skeletal muscle.FEBS Lett.217232–236. [DOI] [PubMed] [Google Scholar]
  29. Rhodes, S. J., and Konieczny, S. F. (1989). Identification of MRF4: A new member of the muscle regulatory factor gene family.Genes Dev.32050–2061. [DOI] [PubMed] [Google Scholar]
  30. Sartorelli, V., Webster, K. A., and Kedes, L. (1990). Muscle-specific expression of the cardiacα-actin gene requires MyoD1, CArG-box binding factor, and Sp1.Genes Dev.41811–1822. [DOI] [PubMed] [Google Scholar]
  31. Shieh, B.-H., Ballivet, M., and Schmidt, J. (1987). Quantitation of anα-subunit splicing intermediate. Evidence for transcriptional activation in the control of receptor expression in denervated chick skeletal muscle.J. Cell Biol.1041337–1341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Shieh, B.-H., Ballivet, M., and Schmidt, J. (1988). Acetylcholine receptor synthesis rate and levels of receptor subunit mRNAs in chick muscle.Neuroscience24175–187. [DOI] [PubMed] [Google Scholar]
  33. Tapscott, S. J., and Weintraub, H. (1991). MyoD and regulation of myogenesis by helix-loop-helix proteins.J. Clin. Invest.871133–1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thayer, M. J., Tapscott, S. J., Davis, R. L., Wright, W. E., Lassar, A. B., and Weintraub, H. (1989). Positive autoregulation of the myogenic determination gene MyoD1.Cell58241–248. [DOI] [PubMed] [Google Scholar]
  35. Tsay, H.-J., Neville, C. M., and Schmidt, J. (1990). Protein synthesis is required for the denervation-triggered activation of acetylcholine receptor genes.FEBS Lett.27469–72. [DOI] [PubMed] [Google Scholar]
  36. Wang, X.-M., Tsay, H.-J., and Schmidt, J. (1990). Expression of the acetylcholine receptorδ subunit gene in differentiating chick muscle cells is activated by an element that contains two 16-bp copies of a segment of theα-subunit enhancer.EMBO J.9738–790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wang, X.-M., Lee, Y.-S., and Schmidt, J. (1991). Analysis of E boxes in the chick muscle acetylcholine receptorδ subunit gene.Soc. Neurosci. Symp.17243. [Google Scholar]
  38. Wang, Y., Xu, H.-P., Wang, X.-M., and Schmidt, J. (1988). A cell type-specific enhancer drives expression of the chick muscle acetylcholine receptorα-subunit gene.Neuron1527–534. [DOI] [PubMed] [Google Scholar]
  39. Witzemann, V., and Sakmann, B. (1991). Differential regulation of MyoD and myogenin mRNA levels by nerve-induced muscle activity.FEBS Lett.282259–264. [DOI] [PubMed] [Google Scholar]
  40. Witzemann, V., Brenner, H.-R., and Sakmann, B. (1991). Neural factors regulate AChR subunit mRNAs at rat neuromuscular synapses.J. Cell Biol.114125–141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wright, W. E., Binder, M., and Funk, W. (1991). Cyclic amplification and selection of targets (CASTing) for myogenin consensus binding site.Mol. Cell. Biol.114104–4110. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Cellular and Molecular Neurobiology are provided here courtesy of Springer

RESOURCES