Skip to main content
Genetics logoLink to Genetics
. 2001 Feb;157(2):639–654. doi: 10.1093/genetics/157.2.639

Conservation of glp-1 regulation and function in nematodes.

D Rudel 1, J Kimble 1
PMCID: PMC1461503  PMID: 11156985

Abstract

The Caenorhabditis elegans (Ce) glp-1 gene encodes a Notch-like receptor. We have cloned glp-1 from C. briggsae (Cb) and C. remanei (Cr), two Caenorhabditis species that have diverged from C. elegans by roughly 20-40 million years. By sequence analysis, we find that the Cb-GLP-1 and Cr-GLP-1 proteins have retained the same motif architecture as Ce-GLP-1, including number of domains. In addition, two regions (CC-linker and regions flanking the ANK repeats) are as highly conserved as regions previously recognized as essential for signaling (e.g., ANK repeats). Phylogenetic analysis of glp-1 sequences suggests a C. briggsae/C. remanei clade with C. elegans as a sister taxon. Using RNAi to test biological functions, we find that Ce-glp-1, Cb-glp-1, and Cr-glp-1 are all required for proliferation of germline stem cells and for specifying blastomere fates in the embryo. In addition, certain biological roles of Cb-glp-1, e.g., in the vulva, have diverged from those of Ce-glp-1 and Cr-glp-1, suggesting a change in either regulation or function of the Cb-glp-1 gene during evolution. Finally, the regulation of glp-1 mRNA, previously analyzed for Ce-glp-1, is conserved in Cb-glp-1, and we identify conserved 3' UTR sequences that may serve as regulatory elements.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

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

  1. Akam M. The Yin and Yang of Evo/Devo. Cell. 1998 Jan 23;92(2):153–155. doi: 10.1016/s0092-8674(00)80909-5. [DOI] [PubMed] [Google Scholar]
  2. Artavanis-Tsakonas S., Matsuno K., Fortini M. E. Notch signaling. Science. 1995 Apr 14;268(5208):225–232. doi: 10.1126/science.7716513. [DOI] [PubMed] [Google Scholar]
  3. Artavanis-Tsakonas S., Rand M. D., Lake R. J. Notch signaling: cell fate control and signal integration in development. Science. 1999 Apr 30;284(5415):770–776. doi: 10.1126/science.284.5415.770. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Batchelor A. H., Piper D. E., de la Brousse F. C., McKnight S. L., Wolberger C. The structure of GABPalpha/beta: an ETS domain- ankyrin repeat heterodimer bound to DNA. Science. 1998 Feb 13;279(5353):1037–1041. doi: 10.1126/science.279.5353.1037. [DOI] [PubMed] [Google Scholar]
  6. Berry L. W., Westlund B., Schedl T. Germ-line tumor formation caused by activation of glp-1, a Caenorhabditis elegans member of the Notch family of receptors. Development. 1997 Feb;124(4):925–936. doi: 10.1242/dev.124.4.925. [DOI] [PubMed] [Google Scholar]
  7. Blaumueller C. M., Qi H., Zagouras P., Artavanis-Tsakonas S. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell. 1997 Jul 25;90(2):281–291. doi: 10.1016/s0092-8674(00)80336-0. [DOI] [PubMed] [Google Scholar]
  8. Blaxter M. Caenorhabditis elegans is a nematode. Science. 1998 Dec 11;282(5396):2041–2046. doi: 10.1126/science.282.5396.2041. [DOI] [PubMed] [Google Scholar]
  9. Bork P. Hundreds of ankyrin-like repeats in functionally diverse proteins: mobile modules that cross phyla horizontally? Proteins. 1993 Dec;17(4):363–374. doi: 10.1002/prot.340170405. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. C. elegans Sequencing Consortium Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012–2018. doi: 10.1126/science.282.5396.2012. [DOI] [PubMed] [Google Scholar]
  12. Christensen S., Kodoyianni V., Bosenberg M., Friedman L., Kimble J. lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H). Development. 1996 May;122(5):1373–1383. doi: 10.1242/dev.122.5.1373. [DOI] [PubMed] [Google Scholar]
  13. Crittenden S. L., Rudel D., Binder J., Evans T. C., Kimble J. Genes required for GLP-1 asymmetry in the early Caenorhabditis elegans embryo. Dev Biol. 1997 Jan 1;181(1):36–46. doi: 10.1006/dbio.1996.8413. [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. 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]
  16. Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 Feb 19;391(6669):806–811. doi: 10.1038/35888. [DOI] [PubMed] [Google Scholar]
  17. Fitch D. H., Bugaj-Gaweda B., Emmons S. W. 18S ribosomal RNA gene phylogeny for some Rhabditidae related to Caenorhabditis. Mol Biol Evol. 1995 Mar;12(2):346–358. doi: 10.1093/oxfordjournals.molbev.a040207. [DOI] [PubMed] [Google Scholar]
  18. Fitzgerald K., Wilkinson H. A., Greenwald I. glp-1 can substitute for lin-12 in specifying cell fate decisions in Caenorhabditis elegans. Development. 1993 Dec;119(4):1019–1027. doi: 10.1242/dev.119.4.1019. [DOI] [PubMed] [Google Scholar]
  19. Goodman M. The genomic record of Humankind's evolutionary roots. Am J Hum Genet. 1999 Jan;64(1):31–39. doi: 10.1086/302218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gorina S., Pavletich N. P. Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science. 1996 Nov 8;274(5289):1001–1005. doi: 10.1126/science.274.5289.1001. [DOI] [PubMed] [Google Scholar]
  21. Greenwald I. S., Sternberg P. W., Horvitz H. R. The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell. 1983 Sep;34(2):435–444. doi: 10.1016/0092-8674(83)90377-x. [DOI] [PubMed] [Google Scholar]
  22. Greenwald I., Seydoux G. Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans. Nature. 1990 Jul 12;346(6280):197–199. doi: 10.1038/346197a0. [DOI] [PubMed] [Google Scholar]
  23. Haag E. S., Kimble J. Regulatory elements required for development of caenorhabditis elegans hermaphrodites are conserved in the tra-2 homologue of C. remanei, a male/female sister species. Genetics. 2000 May;155(1):105–116. doi: 10.1093/genetics/155.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Heitzler P., Simpson P. Altered epidermal growth factor-like sequences provide evidence for a role of Notch as a receptor in cell fate decisions. Development. 1993 Mar;117(3):1113–1123. doi: 10.1242/dev.117.3.1113. [DOI] [PubMed] [Google Scholar]
  25. Henderson S. T., Gao D., Lambie E. J., Kimble J. lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans. Development. 1994 Oct;120(10):2913–2924. doi: 10.1242/dev.120.10.2913. [DOI] [PubMed] [Google Scholar]
  26. Kadyk L. C., Kimble J. Genetic regulation of entry into meiosis in Caenorhabditis elegans. Development. 1998 May;125(10):1803–1813. doi: 10.1242/dev.125.10.1803. [DOI] [PubMed] [Google Scholar]
  27. Kawasaki I., Shim Y. H., Kirchner J., Kaminker J., Wood W. B., Strome S. PGL-1, a predicted RNA-binding component of germ granules, is essential for fertility in C. elegans. Cell. 1998 Sep 4;94(5):635–645. doi: 10.1016/s0092-8674(00)81605-0. [DOI] [PubMed] [Google Scholar]
  28. Kelley M. R., Kidd S., Deutsch W. A., Young M. W. Mutations altering the structure of epidermal growth factor-like coding sequences at the Drosophila Notch locus. Cell. 1987 Nov 20;51(4):539–548. doi: 10.1016/0092-8674(87)90123-1. [DOI] [PubMed] [Google Scholar]
  29. Kennedy B. P., Aamodt E. J., Allen F. L., Chung M. A., Heschl M. F., McGhee J. D. The gut esterase gene (ges-1) from the nematodes Caenorhabditis elegans and Caenorhabditis briggsae. J Mol Biol. 1993 Feb 20;229(4):890–908. doi: 10.1006/jmbi.1993.1094. [DOI] [PubMed] [Google Scholar]
  30. Kimble J., Simpson P. The LIN-12/Notch signaling pathway and its regulation. Annu Rev Cell Dev Biol. 1997;13:333–361. doi: 10.1146/annurev.cellbio.13.1.333. [DOI] [PubMed] [Google Scholar]
  31. Lambie E. J., Kimble J. Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions. Development. 1991 May;112(1):231–240. doi: 10.1242/dev.112.1.231. [DOI] [PubMed] [Google Scholar]
  32. Lardelli M., Lendahl U. Motch A and motch B--two mouse Notch homologues coexpressed in a wide variety of tissues. Exp Cell Res. 1993 Feb;204(2):364–372. doi: 10.1006/excr.1993.1044. [DOI] [PubMed] [Google Scholar]
  33. Logeat F., Bessia C., Brou C., LeBail O., Jarriault S., Seidah N. G., Israël A. The Notch1 receptor is cleaved constitutively by a furin-like convertase. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8108–8112. doi: 10.1073/pnas.95.14.8108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Luh F. Y., Archer S. J., Domaille P. J., Smith B. O., Owen D., Brotherton D. H., Raine A. R., Xu X., Brizuela L., Brenner S. L. Structure of the cyclin-dependent kinase inhibitor p19Ink4d. Nature. 1997 Oct 30;389(6654):999–1003. doi: 10.1038/40202. [DOI] [PubMed] [Google Scholar]
  35. Lyman D., Young M. W. Further evidence for function of the Drosophila Notch protein as a transmembrane receptor. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10395–10399. doi: 10.1073/pnas.90.21.10395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Maine E. M., Lissemore J. L., Starmer W. T. A phylogenetic analysis of vertebrate and invertebrate Notch-related genes. Mol Phylogenet Evol. 1995 Jun;4(2):139–149. doi: 10.1006/mpev.1995.1014. [DOI] [PubMed] [Google Scholar]
  37. Mango S. E., Maine E. M., Kimble J. Carboxy-terminal truncation activates glp-1 protein to specify vulval fates in Caenorhabditis elegans. Nature. 1991 Aug 29;352(6338):811–815. doi: 10.1038/352811a0. [DOI] [PubMed] [Google Scholar]
  38. Mello C. C., Draper B. W., Priess J. R. The maternal genes apx-1 and glp-1 and establishment of dorsal-ventral polarity in the early C. elegans embryo. Cell. 1994 Apr 8;77(1):95–106. doi: 10.1016/0092-8674(94)90238-0. [DOI] [PubMed] [Google Scholar]
  39. Newman A. P., White J. G., Sternberg P. W. The Caenorhabditis elegans lin-12 gene mediates induction of ventral uterine specialization by the anchor cell. Development. 1995 Feb;121(2):263–271. doi: 10.1242/dev.121.2.263. [DOI] [PubMed] [Google Scholar]
  40. Okamoto H., Thomson J. N. Monoclonal antibodies which distinguish certain classes of neuronal and supporting cells in the nervous tissue of the nematode Caenorhabditis elegans. J Neurosci. 1985 Mar;5(3):643–653. doi: 10.1523/JNEUROSCI.05-03-00643.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Petcherski A. G., Kimble J. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature. 2000 May 18;405(6784):364–368. doi: 10.1038/35012645. [DOI] [PubMed] [Google Scholar]
  42. Priess J. R., Thomson J. N. Cellular interactions in early C. elegans embryos. Cell. 1987 Jan 30;48(2):241–250. doi: 10.1016/0092-8674(87)90427-2. [DOI] [PubMed] [Google Scholar]
  43. Puoti A., Kimble J. The Caenorhabditis elegans sex determination gene mog-1 encodes a member of the DEAH-Box protein family. Mol Cell Biol. 1999 Mar;19(3):2189–2197. doi: 10.1128/mcb.19.3.2189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Rand M. D., Grimm L. M., Artavanis-Tsakonas S., Patriub V., Blacklow S. C., Sklar J., Aster J. C. Calcium depletion dissociates and activates heterodimeric notch receptors. Mol Cell Biol. 2000 Mar;20(5):1825–1835. doi: 10.1128/mcb.20.5.1825-1835.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rebay I., Fleming R. J., Fehon R. G., Cherbas L., Cherbas P., Artavanis-Tsakonas S. Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell. 1991 Nov 15;67(4):687–699. doi: 10.1016/0092-8674(91)90064-6. [DOI] [PubMed] [Google Scholar]
  46. Roehl H., Bosenberg M., Blelloch R., Kimble J. Roles of the RAM and ANK domains in signaling by the C. elegans GLP-1 receptor. EMBO J. 1996 Dec 16;15(24):7002–7012. [PMC free article] [PubMed] [Google Scholar]
  47. Roehl H., Kimble J. Control of cell fate in C. elegans by a GLP-1 peptide consisting primarily of ankyrin repeats. Nature. 1993 Aug 12;364(6438):632–635. doi: 10.1038/364632a0. [DOI] [PubMed] [Google Scholar]
  48. Sedgwick S. G., Smerdon S. J. The ankyrin repeat: a diversity of interactions on a common structural framework. Trends Biochem Sci. 1999 Aug;24(8):311–316. doi: 10.1016/s0968-0004(99)01426-7. [DOI] [PubMed] [Google Scholar]
  49. 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]
  50. 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]
  51. Tamura K., Taniguchi Y., Minoguchi S., Sakai T., Tun T., Furukawa T., Honjo T. Physical interaction between a novel domain of the receptor Notch and the transcription factor RBP-J kappa/Su(H). Curr Biol. 1995 Dec 1;5(12):1416–1423. doi: 10.1016/s0960-9822(95)00279-x. [DOI] [PubMed] [Google Scholar]
  52. Tax F. E., Yeargers J. J., Thomas J. H. Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila. Nature. 1994 Mar 10;368(6467):150–154. doi: 10.1038/368150a0. [DOI] [PubMed] [Google Scholar]
  53. Wilkinson H. A., Fitzgerald K., Greenwald I. Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to commitment in a C. elegans cell fate decision. Cell. 1994 Dec 30;79(7):1187–1198. doi: 10.1016/0092-8674(94)90010-8. [DOI] [PubMed] [Google Scholar]
  54. 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]
  55. del Amo F. F., Gendron-Maguire M., Swiatek P. J., Jenkins N. A., Copeland N. G., Gridley T. Cloning, analysis, and chromosomal localization of Notch-1, a mouse homolog of Drosophila Notch. Genomics. 1993 Feb;15(2):259–264. doi: 10.1006/geno.1993.1055. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES