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. 1995 Feb;139(2):607–630. doi: 10.1093/genetics/139.2.607

Analysis of the Multiple Roles of Gld-1 in Germline Development: Interactions with the Sex Determination Cascade and the Glp-1 Signaling Pathway

R Francis 1, E Maine 1, T Schedl 1
PMCID: PMC1206369  PMID: 7713420

Abstract

The Caenorhabditis elegans gene gld-1 is essential for oocyte development; in gld-1 (null) hermaphrodites, a tumor forms where oogenesis would normally occur. We use genetic epistasis analysis to demonstrate that tumor formation is dependent on the sexual fate of the germline. When the germline sex determination pathway is set in the female mode (terminal fem/fog genes inactive), gld-1 (null) germ cells exit meiotic prophase and proliferate to form a tumor, but when the pathway is set in the male mode, they develop into sperm. We conclude that the gld-1 (null) phenotype is cell-type specific and that gld-1 (+) acts at the end of the cascade to direct oogenesis. We also use cell ablation and epistasis analysis to examine the dependence of tumor formation on the glp-1 signaling pathway. Although glp-1 activity promotes tumor growth, it is not essential for tumor formation by gld-1 (null) germ cells. These data also reveal that gld-1 (+) plays a nonessential (and sex nonspecific) role in regulating germ cell proliferation before their entry into meiosis. Thus gld-1 (+) may negatively regulate proliferation at two distinct points in germ cell development: before entry into meiotic prophase in both sexes (nonessential premeiotic gld-1 function) and during meiotic prophase when the sex determination pathway is set in the female mode (essential meiotic gld-1 function).

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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. 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]
  3. 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]
  4. 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]
  5. Bae E., Cook K. R., Geyer P. K., Nagoshi R. N. Molecular characterization of ovarian tumors in Drosophila. Mech Dev. 1994 Aug;47(2):151–164. doi: 10.1016/0925-4773(94)90087-6. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. Carr-Saunders E. M. Letter: Acute respiratory failure in Muslim babies. Br Med J. 1974 Aug 3;3(5926):346–346. doi: 10.1136/bmj.3.5926.346-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. 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]
  13. Evans T. C., Crittenden S. L., Kodoyianni V., Kimble J. Translational control of maternal glp-1 mRNA establishes an asymmetry in the C. elegans embryo. Cell. 1994 Apr 22;77(2):183–194. doi: 10.1016/0092-8674(94)90311-5. [DOI] [PubMed] [Google Scholar]
  14. Francis R., Barton M. K., Kimble J., Schedl T. gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans. Genetics. 1995 Feb;139(2):579–606. doi: 10.1093/genetics/139.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goodwin E. B., Okkema P. G., Evans T. C., Kimble J. Translational regulation of tra-2 by its 3' untranslated region controls sexual identity in C. elegans. Cell. 1993 Oct 22;75(2):329–339. doi: 10.1016/0092-8674(93)80074-o. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Hatano M., Roberts C. W., Minden M., Crist W. M., Korsmeyer S. J. Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. Science. 1991 Jul 5;253(5015):79–82. doi: 10.1126/science.1676542. [DOI] [PubMed] [Google Scholar]
  18. Hodgkin J. A genetic analysis of the sex-determining gene, tra-1, in the nematode Caenorhabditis elegans. Genes Dev. 1987 Sep;1(7):731–745. doi: 10.1101/gad.1.7.731. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. Kodoyianni V., Maine E. M., Kimble J. Molecular basis of loss-of-function mutations in the glp-1 gene of Caenorhabditis elegans. Mol Biol Cell. 1992 Nov;3(11):1199–1213. doi: 10.1091/mbc.3.11.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Rampersaud A., Harlocker S. L., Inouye M. The OmpR protein of Escherichia coli binds to sites in the ompF promoter region in a hierarchical manner determined by its degree of phosphorylation. J Biol Chem. 1994 Apr 29;269(17):12559–12566. [PubMed] [Google Scholar]
  28. Roberts C. W., Shutter J. R., Korsmeyer S. J. Hox11 controls the genesis of the spleen. Nature. 1994 Apr 21;368(6473):747–749. doi: 10.1038/368747a0. [DOI] [PubMed] [Google Scholar]
  29. Schedl T., Graham P. L., Barton M. K., Kimble J. Analysis of the role of tra-1 in germline sex determination in the nematode Caenorhabditis elegans. Genetics. 1989 Dec;123(4):755–769. doi: 10.1093/genetics/123.4.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Seydoux G., Fire A. Soma-germline asymmetry in the distributions of embryonic RNAs in Caenorhabditis elegans. Development. 1994 Oct;120(10):2823–2834. doi: 10.1242/dev.120.10.2823. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. 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]
  35. 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]
  36. Zarkower D., Hodgkin J. Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins. Cell. 1992 Jul 24;70(2):237–249. doi: 10.1016/0092-8674(92)90099-x. [DOI] [PubMed] [Google Scholar]

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