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. 1991 Sep;129(1):79–94. doi: 10.1093/genetics/129.1.79

Genes Required for the Engulfment of Cell Corpses during Programmed Cell Death in Caenorhabditis Elegans

R E Ellis 1, D M Jacobson 1, H R Horvitz 1
PMCID: PMC1204584  PMID: 1936965

Abstract

After programmed cell death, a cell corpse is engulfed and quickly degraded by a neighboring cell. For degradation to occur, engulfing cells must recognize, phagocytose and digest the corpses of dying cells. Previously, three genes were known to be involved in eliminating cell corpses in the nematode Caenorhabditis elegans: ced-1, ced-2 and nuc-1. We have identified five new genes that play a role in this process: ced-5, ced-6, ced-7, ced-8 and ced-10. Electron microscopic studies reveal that mutations in each of these genes prevent engulfment, indicating that these genes are needed either for the recognition of corpses by other cells or for the initiation of phagocytosis. Based upon our study of double mutants, these genes can be divided into two sets. Animals with mutations in only one of these sets of genes have relatively few unengulfed cell corpses. By contrast, animals with mutations in both sets of genes have many unengulfed corpses. These observations suggest that these two sets of genes are involved in distinct and partially redundant processes that act in the engulfment of cell corpses.

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Selected References

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  1. Austin J., Kimble J. glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell. 1987 Nov 20;51(4):589–599. doi: 10.1016/0092-8674(87)90128-0. [DOI] [PubMed] [Google Scholar]
  2. Avery L., Horvitz H. R. A cell that dies during wild-type C. elegans development can function as a neuron in a ced-3 mutant. Cell. 1987 Dec 24;51(6):1071–1078. doi: 10.1016/0092-8674(87)90593-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chalfie M., Sulston J. Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev Biol. 1981 Mar;82(2):358–370. doi: 10.1016/0012-1606(81)90459-0. [DOI] [PubMed] [Google Scholar]
  4. Clark D. V., Rogalski T. M., Donati L. M., Baillie D. L. The unc-22(IV) region of Caenorhabditis elegans: genetic analysis of lethal mutations. Genetics. 1988 Jun;119(2):345–353. doi: 10.1093/genetics/119.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Collins J., Saari B., Anderson P. Activation of a transposable element in the germ line but not the soma of Caenorhabditis elegans. Nature. 1987 Aug 20;328(6132):726–728. doi: 10.1038/328726a0. [DOI] [PubMed] [Google Scholar]
  6. Cowan W. M., Fawcett J. W., O'Leary D. D., Stanfield B. B. Regressive events in neurogenesis. Science. 1984 Sep 21;225(4668):1258–1265. doi: 10.1126/science.6474175. [DOI] [PubMed] [Google Scholar]
  7. Desai C., Horvitz H. R. Caenorhabditis elegans mutants defective in the functioning of the motor neurons responsible for egg laying. Genetics. 1989 Apr;121(4):703–721. doi: 10.1093/genetics/121.4.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Duvall E., Wyllie A. H., Morris R. G. Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology. 1985 Oct;56(2):351–358. [PMC free article] [PubMed] [Google Scholar]
  9. Ellis H. M., Horvitz H. R. Genetic control of programmed cell death in the nematode C. elegans. Cell. 1986 Mar 28;44(6):817–829. doi: 10.1016/0092-8674(86)90004-8. [DOI] [PubMed] [Google Scholar]
  10. Ellis R. E., Horvitz H. R. Two C. elegans genes control the programmed deaths of specific cells in the pharynx. Development. 1991 Jun;112(2):591–603. doi: 10.1242/dev.112.2.591. [DOI] [PubMed] [Google Scholar]
  11. Ferguson E. L., Horvitz H. R. Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans. Genetics. 1985 May;110(1):17–72. doi: 10.1093/genetics/110.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Greenwald I. S., Horvitz H. R. unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype. Genetics. 1980 Sep;96(1):147–164. doi: 10.1093/genetics/96.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hedgecock E. M., Sulston J. E., Thomson J. N. Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans. Science. 1983 Jun 17;220(4603):1277–1279. doi: 10.1126/science.6857247. [DOI] [PubMed] [Google Scholar]
  14. Hodgkin J., Horvitz H. R., Brenner S. Nondisjunction Mutants of the Nematode CAENORHABDITIS ELEGANS. Genetics. 1979 Jan;91(1):67–94. doi: 10.1093/genetics/91.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Horvitz H. R., Brenner S., Hodgkin J., Herman R. K. A uniform genetic nomenclature for the nematode Caenorhabditis elegans. Mol Gen Genet. 1979 Sep;175(2):129–133. doi: 10.1007/BF00425528. [DOI] [PubMed] [Google Scholar]
  16. Horvitz H. R., Sulston J. E. Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. Genetics. 1980 Oct;96(2):435–454. doi: 10.1093/genetics/96.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kemphues K. J., Priess J. R., Morton D. G., Cheng N. S. Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell. 1988 Feb 12;52(3):311–320. doi: 10.1016/s0092-8674(88)80024-2. [DOI] [PubMed] [Google Scholar]
  18. Kimble J., Hirsh D. The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Dev Biol. 1979 Jun;70(2):396–417. doi: 10.1016/0012-1606(79)90035-6. [DOI] [PubMed] [Google Scholar]
  19. Miller L. M., Plenefisch J. D., Casson L. P., Meyer B. J. xol-1: a gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans. Cell. 1988 Oct 7;55(1):167–183. doi: 10.1016/0092-8674(88)90019-0. [DOI] [PubMed] [Google Scholar]
  20. Moerman D. G., Baillie D. L. Formaldehyde mutagenesis in the nematode Caenorhabditis elegans. Mutat Res. 1981 Feb;80(2):273–279. doi: 10.1016/0027-5107(81)90100-7. [DOI] [PubMed] [Google Scholar]
  21. Moerman D. G., Baillie D. L. Genetic Organization in CAENORHABDITIS ELEGANS: Fine-Structure Analysis of the unc-22 Gene. Genetics. 1979 Jan;91(1):95–103. doi: 10.1093/genetics/91.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rogalski T. M., Baillie D. L. Genetic organization of the unc-22 IV gene and the adjacent region in Caenorhabditis elegans. Mol Gen Genet. 1985;201(3):409–414. doi: 10.1007/BF00331331. [DOI] [PubMed] [Google Scholar]
  23. Rogalski T. M., Moerman D. G., Baillie D. L. Essential genes and deficiencies in the unc-22 IV region of Caenorhabditis elegans. Genetics. 1982 Dec;102(4):725–736. doi: 10.1093/genetics/102.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saunders J. W., Jr Death in embryonic systems. Science. 1966 Nov 4;154(3749):604–612. doi: 10.1126/science.154.3749.604. [DOI] [PubMed] [Google Scholar]
  25. Savage C., Hamelin M., Culotti J. G., Coulson A., Albertson D. G., Chalfie M. mec-7 is a beta-tubulin gene required for the production of 15-protofilament microtubules in Caenorhabditis elegans. Genes Dev. 1989 Jun;3(6):870–881. doi: 10.1101/gad.3.6.870. [DOI] [PubMed] [Google Scholar]
  26. Savill J., Dransfield I., Hogg N., Haslett C. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature. 1990 Jan 11;343(6254):170–173. doi: 10.1038/343170a0. [DOI] [PubMed] [Google Scholar]
  27. Sternberg P. W., Horvitz H. R. Gonadal cell lineages of the nematode Panagrellus redivivus and implications for evolution by the modification of cell lineage. Dev Biol. 1981 Nov;88(1):147–166. doi: 10.1016/0012-1606(81)90226-8. [DOI] [PubMed] [Google Scholar]
  28. Stocker R. F., Edwards J. S., Truman J. W. Fine structure of degenerating abdominal motor neurons after eclosion in the sphingid moth, Manduca sexta. Cell Tissue Res. 1978 Jul 27;191(2):317–331. doi: 10.1007/BF00222427. [DOI] [PubMed] [Google Scholar]
  29. Sulston J. E., Brenner S. The DNA of Caenorhabditis elegans. Genetics. 1974 May;77(1):95–104. doi: 10.1093/genetics/77.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sulston J. E., Horvitz H. R. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev Biol. 1977 Mar;56(1):110–156. doi: 10.1016/0012-1606(77)90158-0. [DOI] [PubMed] [Google Scholar]
  31. Sulston J. E. Post-embryonic development in the ventral cord of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci. 1976 Aug 10;275(938):287–297. doi: 10.1098/rstb.1976.0084. [DOI] [PubMed] [Google Scholar]
  32. Sulston J. E., White J. G. Regulation and cell autonomy during postembryonic development of Caenorhabditis elegans. Dev Biol. 1980 Aug;78(2):577–597. doi: 10.1016/0012-1606(80)90353-x. [DOI] [PubMed] [Google Scholar]
  33. Truman J. W. Cell death in invertebrate nervous systems. Annu Rev Neurosci. 1984;7:171–188. doi: 10.1146/annurev.ne.07.030184.001131. [DOI] [PubMed] [Google Scholar]
  34. Yuan J. Y., Horvitz H. R. The Caenorhabditis elegans genes ced-3 and ced-4 act cell autonomously to cause programmed cell death. Dev Biol. 1990 Mar;138(1):33–41. doi: 10.1016/0012-1606(90)90174-h. [DOI] [PubMed] [Google Scholar]

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