Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1994 Feb 2;124(4):475–490. doi: 10.1083/jcb.124.4.475

Genes critical for muscle development and function in Caenorhabditis elegans identified through lethal mutations

PMCID: PMC2119919  PMID: 8106547

Abstract

By taking advantage of a lethal phenotype characteristic of Caenorhabditis elegans embryos that fail to move, we have identified 13 genes required for muscle assembly and function and discovered a new lethal class of alleles for three previously known muscle-affecting genes. By staining mutant embryos for myosin and actin we have recognized five distinct classes of genes: mutations in four genes disrupt the assembly of thick and thin filaments into the myofilament lattice as well as the polarized location of these components to the sarcolemma. Mutations in another three genes also disrupt thick and thin filament assembly, but allow proper polarization of lattice components based on the myosin heavy chain isoform that we analyzed. Another two classes of genes are defined by mutations with principal effects on thick or thin filament assembly into the lattice, but not both. The final class includes three genes in which mutations cause relatively minor defects in lattice assembly. Failure of certain mutants to stain with antibodies to specific muscle cell antigens suggest that two genes associated with severe disruptions of myofilament lattice assembly may code for components of the basement membrane and the sarcolemma that are concentrated where dense bodies (Z- line analogs) and M-lines attach to the cell membrane. Similar evidence suggests that one of the genes associated with mild effects on lattice assembly may code for tropomyosin. Many of the newly identified genes are likely to play critical roles in muscle development and function.

Full Text

The Full Text of this article is available as a PDF (4.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ardizzi J. P., Epstein H. F. Immunochemical localization of myosin heavy chain isoforms and paramyosin in developmentally and structurally diverse muscle cell types of the nematode Caenorhabditis elegans. J Cell Biol. 1987 Dec;105(6 Pt 1):2763–2770. doi: 10.1083/jcb.105.6.2763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barstead R. J., Kleiman L., Waterston R. H. Cloning, sequencing, and mapping of an alpha-actinin gene from the nematode Caenorhabditis elegans. Cell Motil Cytoskeleton. 1991;20(1):69–78. doi: 10.1002/cm.970200108. [DOI] [PubMed] [Google Scholar]
  3. Barstead R. J., Waterston R. H. The basal component of the nematode dense-body is vinculin. J Biol Chem. 1989 Jun 15;264(17):10177–10185. [PubMed] [Google Scholar]
  4. Barstead R. J., Waterston R. H. Vinculin is essential for muscle function in the nematode. J Cell Biol. 1991 Aug;114(4):715–724. doi: 10.1083/jcb.114.4.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beall C. J., Sepanski M. A., Fyrberg E. A. Genetic dissection of Drosophila myofibril formation: effects of actin and myosin heavy chain null alleles. Genes Dev. 1989 Feb;3(2):131–140. doi: 10.1101/gad.3.2.131. [DOI] [PubMed] [Google Scholar]
  6. Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Casella J. F., Craig S. W., Maack D. J., Brown A. E. Cap Z(36/32), a barbed end actin-capping protein, is a component of the Z-line of skeletal muscle. J Cell Biol. 1987 Jul;105(1):371–379. doi: 10.1083/jcb.105.1.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen L., Krause M., Draper B., Weintraub H., Fire A. Body-wall muscle formation in Caenorhabditis elegans embryos that lack the MyoD homolog hlh-1. Science. 1992 Apr 10;256(5054):240–243. doi: 10.1126/science.1314423. [DOI] [PubMed] [Google Scholar]
  9. Cummins C., Anderson P. Regulatory myosin light-chain genes of Caenorhabditis elegans. Mol Cell Biol. 1988 Dec;8(12):5339–5349. doi: 10.1128/mcb.8.12.5339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Epstein H. F., Waterston R. H., Brenner S. A mutant affecting the heavy chain of myosin in Caenorhabditis elegans. J Mol Biol. 1974 Dec 5;90(2):291–300. doi: 10.1016/0022-2836(74)90374-x. [DOI] [PubMed] [Google Scholar]
  11. Francis G. R., Waterston R. H. Muscle organization in Caenorhabditis elegans: localization of proteins implicated in thin filament attachment and I-band organization. J Cell Biol. 1985 Oct;101(4):1532–1549. doi: 10.1083/jcb.101.4.1532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Francis R., Waterston R. H. Muscle cell attachment in Caenorhabditis elegans. J Cell Biol. 1991 Aug;114(3):465–479. doi: 10.1083/jcb.114.3.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guo X. D., Johnson J. J., Kramer J. M. Embryonic lethality caused by mutations in basement membrane collagen of C. elegans. Nature. 1991 Feb 21;349(6311):707–709. doi: 10.1038/349707a0. [DOI] [PubMed] [Google Scholar]
  14. Lewis J. A., Wu C. H., Berg H., Levine J. H. The genetics of levamisole resistance in the nematode Caenorhabditis elegans. Genetics. 1980 Aug;95(4):905–928. doi: 10.1093/genetics/95.4.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MacKrell A. J., Blumberg B., Haynes S. R., Fessler J. H. The lethal myospheroid gene of Drosophila encodes a membrane protein homologous to vertebrate integrin beta subunits. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2633–2637. doi: 10.1073/pnas.85.8.2633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miller D. M., 3rd, Ortiz I., Berliner G. C., Epstein H. F. Differential localization of two myosins within nematode thick filaments. Cell. 1983 Sep;34(2):477–490. doi: 10.1016/0092-8674(83)90381-1. [DOI] [PubMed] [Google Scholar]
  17. Miwa J., Schierenberg E., Miwa S., von Ehrenstein G. Genetics and mode of expression of temperature-sensitive mutations arresting embryonic development in Caenorhabditis elegans. Dev Biol. 1980 Apr;76(1):160–174. doi: 10.1016/0012-1606(80)90369-3. [DOI] [PubMed] [Google Scholar]
  18. Newman S. M., Jr, Wright T. R. A histological and ultrastructural analysis of developmental defects produced by the mutation, lethal(1)myospheroid, in Drosophila melanogaster. Dev Biol. 1981 Sep;86(2):393–402. doi: 10.1016/0012-1606(81)90197-4. [DOI] [PubMed] [Google Scholar]
  19. Priess J. R., Hirsh D. I. Caenorhabditis elegans morphogenesis: the role of the cytoskeleton in elongation of the embryo. Dev Biol. 1986 Sep;117(1):156–173. doi: 10.1016/0012-1606(86)90358-1. [DOI] [PubMed] [Google Scholar]
  20. Rogalski T. M., Williams B. D., Mullen G. P., Moerman D. G. Products of the unc-52 gene in Caenorhabditis elegans are homologous to the core protein of the mammalian basement membrane heparan sulfate proteoglycan. Genes Dev. 1993 Aug;7(8):1471–1484. doi: 10.1101/gad.7.8.1471. [DOI] [PubMed] [Google Scholar]
  21. Sibley M. H., Johnson J. J., Mello C. C., Kramer J. M. Genetic identification, sequence, and alternative splicing of the Caenorhabditis elegans alpha 2(IV) collagen gene. J Cell Biol. 1993 Oct;123(1):255–264. doi: 10.1083/jcb.123.1.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sulston J. E., Schierenberg E., White J. G., Thomson J. N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol. 1983 Nov;100(1):64–119. doi: 10.1016/0012-1606(83)90201-4. [DOI] [PubMed] [Google Scholar]
  23. Sulston J., Du Z., Thomas K., Wilson R., Hillier L., Staden R., Halloran N., Green P., Thierry-Mieg J., Qiu L. The C. elegans genome sequencing project: a beginning. Nature. 1992 Mar 5;356(6364):37–41. doi: 10.1038/356037a0. [DOI] [PubMed] [Google Scholar]
  24. Toyama Y., Forry-Schaudies S., Hoffman B., Holtzer H. Effects of taxol and Colcemid on myofibrillogenesis. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6556–6560. doi: 10.1073/pnas.79.21.6556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Venolia L., Waterston R. H. The unc-45 gene of Caenorhabditis elegans is an essential muscle-affecting gene with maternal expression. Genetics. 1990 Oct;126(2):345–353. doi: 10.1093/genetics/126.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Volk T., Fessler L. I., Fessler J. H. A role for integrin in the formation of sarcomeric cytoarchitecture. Cell. 1990 Nov 2;63(3):525–536. doi: 10.1016/0092-8674(90)90449-o. [DOI] [PubMed] [Google Scholar]
  27. WRIGHT T. R. The phenogenetics of the embryonic mutant, lethal myospheroid, in Drosophila melanogaster. J Exp Zool. 1960 Feb;143:77–99. doi: 10.1002/jez.1401430107. [DOI] [PubMed] [Google Scholar]
  28. Waddle J. A., Cooper J. A., Waterston R. H. The alpha and beta subunits of nematode actin capping protein function in yeast. Mol Biol Cell. 1993 Sep;4(9):907–917. doi: 10.1091/mbc.4.9.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Waterston R. H., Hirsh D., Lane T. R. Dominant mutations affecting muscle structure in Caenorhabditis elegans that map near the actin gene cluster. J Mol Biol. 1984 Dec 15;180(3):473–496. doi: 10.1016/0022-2836(84)90023-8. [DOI] [PubMed] [Google Scholar]
  30. Waterston R. H. The minor myosin heavy chain, mhcA, of Caenorhabditis elegans is necessary for the initiation of thick filament assembly. EMBO J. 1989 Nov;8(11):3429–3436. doi: 10.1002/j.1460-2075.1989.tb08507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Waterston R. H., Thomson J. N., Brenner S. Mutants with altered muscle structure of Caenorhabditis elegans. Dev Biol. 1980 Jun 15;77(2):271–302. doi: 10.1016/0012-1606(80)90475-3. [DOI] [PubMed] [Google Scholar]
  32. Williams B. D., Schrank B., Huynh C., Shownkeen R., Waterston R. H. A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites. Genetics. 1992 Jul;131(3):609–624. doi: 10.1093/genetics/131.3.609. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES