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. 1995 Feb;139(2):579–606. doi: 10.1093/genetics/139.2.579

Gld-1, a Tumor Suppressor Gene Required for Oocyte Development in Caenorhabditis Elegans

R Francis 1, M K Barton 1, J Kimble 1, T Schedl 1
PMCID: PMC1206368  PMID: 7713419

Abstract

We have characterized 31 mutations in the gld-1 (defective in germline development) gene of Caenorhabditis elegans. In gld-1(null) hermaphrodites, oogenesis is abolished and a germline tumor forms where oocyte development would normally occur. By contrast, gld-1(null) males are unaffected. The hermaphrodite germline tumor appears to derive from germ cells that enter the meiotic pathway normally but then exit pachytene and return to the mitotic cycle. Certain gld-1 partial loss-of-function mutations also abolish oogenesis, but germ cells arrest in pachytene rather than returning to mitosis. Our results indicate that gld-1 is a tumor suppressor gene required for oocyte development. The tumorous phenotype suggests that gld-1(+) may function to negatively regulate proliferation during meiotic prophase and/or act to direct progression through meiotic prophase. We also show that gld-1(+) has an additional nonessential role in germline sex determination: promotion of hermaphrodite spermatogenesis. This function of gld-1 is inferred from a haplo-insufficient phenotype and from the properties of gain-of-function gld-1 mutations that cause alterations in the sexual identity of germ cells.

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Selected References

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  1. Ahringer J., Kimble J. Control of the sperm-oocyte switch in Caenorhabditis elegans hermaphrodites by the fem-3 3' untranslated region. Nature. 1991 Jan 24;349(6307):346–348. doi: 10.1038/349346a0. [DOI] [PubMed] [Google Scholar]
  2. Albertson D. G. Formation of the first cleavage spindle in nematode embryos. Dev Biol. 1984 Jan;101(1):61–72. doi: 10.1016/0012-1606(84)90117-9. [DOI] [PubMed] [Google Scholar]
  3. Albertson D. G., Thomson J. N. Segregation of holocentric chromosomes at meiosis in the nematode, Caenorhabditis elegans. Chromosome Res. 1993 May;1(1):15–26. doi: 10.1007/BF00710603. [DOI] [PubMed] [Google Scholar]
  4. Andersson S., Saebøe-Larssen S., Lambertsson A., Merriam J., Jacobs-Lorena M. A Drosophila third chromosome Minute locus encodes a ribosomal protein. Genetics. 1994 Jun;137(2):513–520. doi: 10.1093/genetics/137.2.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Austin J., Kimble J. Transcript analysis of glp-1 and lin-12, homologous genes required for cell interactions during development of C. elegans. Cell. 1989 Aug 11;58(3):565–571. doi: 10.1016/0092-8674(89)90437-6. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Barton M. K., Kimble J. fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans. Genetics. 1990 May;125(1):29–39. doi: 10.1093/genetics/125.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Barton M. K., Schedl T. B., Kimble J. Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans. Genetics. 1987 Jan;115(1):107–119. doi: 10.1093/genetics/115.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Beanan M. J., Strome S. Characterization of a germ-line proliferation mutation in C. elegans. Development. 1992 Nov;116(3):755–766. doi: 10.1242/dev.116.3.755. [DOI] [PubMed] [Google Scholar]
  10. Capowski E. E., Martin P., Garvin C., Strome S. Identification of grandchildless loci whose products are required for normal germ-line development in the nematode Caenorhabditis elegans. Genetics. 1991 Dec;129(4):1061–1072. doi: 10.1093/genetics/129.4.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Carpenter A. T. Egalitarian and the choice of cell fates in Drosophila melanogaster oogenesis. Ciba Found Symp. 1994;182:223–254. [PubMed] [Google Scholar]
  12. Carritt B., Parrington J. M., Welch H. M., Povey S. Diverse origins of multiple ovarian teratomas in a single individual. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7400–7404. doi: 10.1073/pnas.79.23.7400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Crittenden S. L., Troemel E. R., Evans T. C., Kimble J. GLP-1 is localized to the mitotic region of the C. elegans germ line. Development. 1994 Oct;120(10):2901–2911. doi: 10.1242/dev.120.10.2901. [DOI] [PubMed] [Google Scholar]
  15. Doniach T. Activity of the sex-determining gene tra-2 is modulated to allow spermatogenesis in the C. elegans hermaphrodite. Genetics. 1986 Sep;114(1):53–76. doi: 10.1093/genetics/114.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Doniach T., Hodgkin J. A sex-determining gene, fem-1, required for both male and hermaphrodite development in Caenorhabditis elegans. Dev Biol. 1984 Nov;106(1):223–235. doi: 10.1016/0012-1606(84)90077-0. [DOI] [PubMed] [Google Scholar]
  17. Eppig J. J., Kozak L. P., Eicher E. M., Stevens L. C. Ovarian teratomas in mice are derived from oocytes that have completed the first meiotic division. Nature. 1977 Oct 6;269(5628):517–518. doi: 10.1038/269517a0. [DOI] [PubMed] [Google Scholar]
  18. Fisher E., Scambler P. Human haploinsufficiency--one for sorrow, two for joy. Nat Genet. 1994 May;7(1):5–7. doi: 10.1038/ng0594-5. [DOI] [PubMed] [Google Scholar]
  19. Graham P. L., Kimble J. The mog-1 gene is required for the switch from spermatogenesis to oogenesis in Caenorhabditis elegans. Genetics. 1993 Apr;133(4):919–931. doi: 10.1093/genetics/133.4.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Graham P. L., Schedl T., Kimble J. More mog genes that influence the switch from spermatogenesis to oogenesis in the hermaphrodite germ line of Caenorhabditis elegans. Dev Genet. 1993;14(6):471–484. doi: 10.1002/dvg.1020140608. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Hashimoto N., Watanabe N., Furuta Y., Tamemoto H., Sagata N., Yokoyama M., Okazaki K., Nagayoshi M., Takeda N., Ikawa Y. Parthenogenetic activation of oocytes in c-mos-deficient mice. Nature. 1994 Jul 7;370(6484):68–71. doi: 10.1038/370068a0. [DOI] [PubMed] [Google Scholar]
  23. Hirsh D., Oppenheim D., Klass M. Development of the reproductive system of Caenorhabditis elegans. Dev Biol. 1976 Mar;49(1):200–219. doi: 10.1016/0012-1606(76)90267-0. [DOI] [PubMed] [Google Scholar]
  24. Hodgkin J. Fluxes, doses and poisons: molecular perspectives on dominance. Trends Genet. 1993 Jan;9(1):1–2. doi: 10.1016/0168-9525(93)90050-R. [DOI] [PubMed] [Google Scholar]
  25. Hodgkin J. More sex-determination mutants of Caenorhabditis elegans. Genetics. 1980 Nov;96(3):649–664. doi: 10.1093/genetics/96.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hodgkin J. Sex determination in the nematode C. elegans: analysis of tra-3 suppressors and characterization of fem genes. Genetics. 1986 Sep;114(1):15–52. doi: 10.1093/genetics/114.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Honigberg S. M., Conicella C., Espositio R. E. Commitment to meiosis in Saccharomyces cerevisiae: involvement of the SPO14 gene. Genetics. 1992 Apr;130(4):703–716. doi: 10.1093/genetics/130.4.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Honigberg S. M., Esposito R. E. Reversal of cell determination in yeast meiosis: postcommitment arrest allows return to mitotic growth. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6559–6563. doi: 10.1073/pnas.91.14.6559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Jarry B. P. Genetical and cytological location of the structural parts coding for the first three steps of pyrimidine biosynthesis in Drosophila melanogaster. Mol Gen Genet. 1979 May 4;172(2):199–202. doi: 10.1007/BF00268283. [DOI] [PubMed] [Google Scholar]
  31. Kimble J. E., White J. G. On the control of germ cell development in Caenorhabditis elegans. Dev Biol. 1981 Jan 30;81(2):208–219. doi: 10.1016/0012-1606(81)90284-0. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Klass M., Wolf N., Hirsh D. Development of the male reproductive system and sexual transformation in the nematode Caenorhabditis elegans. Dev Biol. 1976 Aug;52(1):1–18. doi: 10.1016/0012-1606(76)90002-6. [DOI] [PubMed] [Google Scholar]
  34. Kuwabara P. E., Kimble J. Molecular genetics of sex determination in C. elegans. Trends Genet. 1992 May;8(5):164–168. doi: 10.1016/0168-9525(92)90218-s. [DOI] [PubMed] [Google Scholar]
  35. Kuwabara P. E., Okkema P. G., Kimble J. tra-2 encodes a membrane protein and may mediate cell communication in the Caenorhabditis elegans sex determination pathway. Mol Biol Cell. 1992 Apr;3(4):461–473. doi: 10.1091/mbc.3.4.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. L'Hernault S. W., Shakes D. C., Ward S. Developmental genetics of chromosome I spermatogenesis-defective mutants in the nematode Caenorhabditis elegans. Genetics. 1988 Oct;120(2):435–452. doi: 10.1093/genetics/120.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Madl J. E., Herman R. K. Polyploids and sex determination in Caenorhabditis elegans. Genetics. 1979 Oct;93(2):393–402. doi: 10.1093/genetics/93.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Mains P. E., Sulston I. A., Wood W. B. Dominant maternal-effect mutations causing embryonic lethality in Caenorhabditis elegans. Genetics. 1990 Jun;125(2):351–369. doi: 10.1093/genetics/125.2.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Malone R. E. Dual regulation of meiosis in yeast. Cell. 1990 May 4;61(3):375–378. doi: 10.1016/0092-8674(90)90517-i. [DOI] [PubMed] [Google Scholar]
  41. McKim K. S., Starr T., Rose A. M. Genetic and molecular analysis of the dpy-14 region in Caenorhabditis elegans. Mol Gen Genet. 1992 May;233(1-2):241–251. doi: 10.1007/BF00587585. [DOI] [PubMed] [Google Scholar]
  42. Nelson G. A., Lew K. K., Ward S. Intersex, a temperature-sensitive mutant of the nematode Caenorhabditis elegans. Dev Biol. 1978 Oct;66(2):386–409. doi: 10.1016/0012-1606(78)90247-6. [DOI] [PubMed] [Google Scholar]
  43. Parrington J. M., West L. F., Povey S. The origin of ovarian teratomas. J Med Genet. 1984 Feb;21(1):4–12. doi: 10.1136/jmg.21.1.4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schedl T., Kimble J. fog-2, a germ-line-specific sex determination gene required for hermaphrodite spermatogenesis in Caenorhabditis elegans. Genetics. 1988 May;119(1):43–61. doi: 10.1093/genetics/119.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Schejter E. D., Shilo B. Z. The Drosophila EGF receptor homolog (DER) gene is allelic to faint little ball, a locus essential for embryonic development. Cell. 1989 Mar 24;56(6):1093–1104. doi: 10.1016/0092-8674(89)90642-9. [DOI] [PubMed] [Google Scholar]
  46. Seydoux G., Schedl T., Greenwald I. Cell-cell interactions prevent a potential inductive interaction between soma and germline in C. elegans. Cell. 1990 Jun 15;61(6):939–951. doi: 10.1016/0092-8674(90)90060-r. [DOI] [PubMed] [Google Scholar]
  47. Stewart B. R., Merriam J. R. Segmental aneuploidy and enzyme activity as a method for cytogenetic localization in drosophila melanogaster. Genetics. 1974 Feb;76(2):301–309. doi: 10.1093/genetics/76.2.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Strome S. Fluorescence visualization of the distribution of microfilaments in gonads and early embryos of the nematode Caenorhabditis elegans. J Cell Biol. 1986 Dec;103(6 Pt 1):2241–2252. doi: 10.1083/jcb.103.6.2241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Surti U., Hoffner L., Chakravarti A., Ferrell R. E. Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin. Am J Hum Genet. 1990 Oct;47(4):635–643. [PMC free article] [PubMed] [Google Scholar]
  50. Thomas J. H. Genetic analysis of defecation in Caenorhabditis elegans. Genetics. 1990 Apr;124(4):855–872. doi: 10.1093/genetics/124.4.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Van Vactor D., Jr, Krantz D. E., Reinke R., Zipursky S. L. Analysis of mutants in chaoptin, a photoreceptor cell-specific glycoprotein in Drosophila, reveals its role in cellular morphogenesis. Cell. 1988 Jan 29;52(2):281–290. doi: 10.1016/0092-8674(88)90517-x. [DOI] [PubMed] [Google Scholar]
  52. Villeneuve A. M., Meyer B. J. The regulatory hierarchy controlling sex determination and dosage compensation in Caenorhabditis elegans. Adv Genet. 1990;27:117–188. doi: 10.1016/s0065-2660(08)60025-5. [DOI] [PubMed] [Google Scholar]
  53. Ward S., Carrel J. S. Fertilization and sperm competition in the nematode Caenorhabditis elegans. Dev Biol. 1979 Dec;73(2):304–321. doi: 10.1016/0012-1606(79)90069-1. [DOI] [PubMed] [Google Scholar]
  54. Ward S., Roberts T. M., Strome S., Pavalko F. M., Hogan E. Monoclonal antibodies that recognize a polypeptide antigenic determinant shared by multiple Caenorhabditis elegans sperm-specific proteins. J Cell Biol. 1986 May;102(5):1778–1786. doi: 10.1083/jcb.102.5.1778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]
  56. Yochem J., Greenwald I. glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins. Cell. 1989 Aug 11;58(3):553–563. doi: 10.1016/0092-8674(89)90436-4. [DOI] [PubMed] [Google Scholar]

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