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Philos Trans R Soc Lond B Biol Sci. Aug 29, 2003; 358(1436): 1359–1362.
PMCID: PMC1693240

Regulation of the mitosis/meiosis decision in the Caenorhabditis elegans germline.

Abstract

During the development of multicellular organisms, the processes of growth and differentiation are kept in balance to generate and maintain tissues and organs of the correct size, shape and cellular composition. We have investigated the molecular controls of growth and differentiation in the Caenorhabditis elegans germline. A single somatic cell, called the distal tip cell, promotes mitotic proliferation in the adjacent germline by GLP-1/Notch signalling. Within the germline, the decisions between mitosis and meiosis and between spermatogenesis and oogenesis are controlled by a group of conserved RNA regulators. FBF, a member of the PUF (for Pumilio and FBF) family of RNA-binding proteins, promotes mitosis by repressing gld-1 mRNA activity; the GLD-1, GLD-2, GLD-3 and NOS-3 proteins promote entry into meiosis by regulating mRNAs that remain unknown. The regulatory balance between opposing FBF and GLD activities is crucial for controlling the extent of germline proliferation. PUF proteins regulate germline stem cells in both Drosophila and C. elegans and are localized to germline stem cells of the mammalian testis. Therefore, this post-transcriptional regulatory switch may be an ancient mechanism for controlling maintenance of stem cells versus differentiation.

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Selected References

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  • Baonza A, Garcia-Bellido A. Notch signaling directly controls cell proliferation in the Drosophila wing disc. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2609–2614. [PMC free article] [PubMed]
  • Berry LW, 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. [PubMed]
  • 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. [PubMed]
  • Conboy Irina M, Rando Thomas A. The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev Cell. 2002 Sep;3(3):397–409. [PubMed]
  • Crittenden SL, Troemel ER, Evans TC, Kimble J. GLP-1 is localized to the mitotic region of the C. elegans germ line. Development. 1994 Oct;120(10):2901–2911. [PubMed]
  • Crittenden Sarah L, Bernstein David S, Bachorik Jennifer L, Thompson Beth E, Gallegos Maria, Petcherski Andrei G, Moulder Gary, Barstead Robert, Wickens Marvin, Kimble Judith. A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans. Nature. 2002 Jun 6;417(6889):660–663. [PubMed]
  • Eckmann Christian R, Kraemer Brian, Wickens Marvin, Kimble Judith. GLD-3, a bicaudal-C homolog that inhibits FBF to control germline sex determination in C. elegans. Dev Cell. 2002 Nov;3(5):697–710. [PubMed]
  • Forbes A, Lehmann R. Nanos and Pumilio have critical roles in the development and function of Drosophila germline stem cells. Development. 1998 Feb;125(4):679–690. [PubMed]
  • Francis R, Barton MK, Kimble J, Schedl T. gld-1, a tumor suppressor gene required for oocyte development in Caenorhabditis elegans. Genetics. 1995 Feb;139(2):579–606. [PMC free article] [PubMed]
  • Henderson ST, Gao D, Lambie EJ, 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. [PubMed]
  • Henderson ST, Gao D, Christensen S, Kimble J. Functional domains of LAG-2, a putative signaling ligand for LIN-12 and GLP-1 receptors in Caenorhabditis elegans. Mol Biol Cell. 1997 Sep;8(9):1751–1762. [PMC free article] [PubMed]
  • Jan E, Motzny CK, Graves LE, Goodwin EB. The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans. EMBO J. 1999 Jan 4;18(1):258–269. [PMC free article] [PubMed]
  • Jones AR, Schedl T. Mutations in gld-1, a female germ cell-specific tumor suppressor gene in Caenorhabditis elegans, affect a conserved domain also found in Src-associated protein Sam68. Genes Dev. 1995 Jun 15;9(12):1491–1504. [PubMed]
  • Kadyk LC, Kimble J. Genetic regulation of entry into meiosis in Caenorhabditis elegans. Development. 1998 May;125(10):1803–1813. [PubMed]
  • Kennedy BK, Gotta M, Sinclair DA, Mills K, McNabb DS, Murthy M, Pak SM, Laroche T, Gasser SM, Guarente L. Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell. 1997 May 2;89(3):381–391. [PubMed]
  • Kimble J, Simpson P. The LIN-12/Notch signaling pathway and its regulation. Annu Rev Cell Dev Biol. 1997;13:333–361. [PubMed]
  • Kimble JE, White JG. On the control of germ cell development in Caenorhabditis elegans. Dev Biol. 1981 Jan 30;81(2):208–219. [PubMed]
  • Kipreos ET, Gohel SP, Hedgecock EM. The C. elegans F-box/WD-repeat protein LIN-23 functions to limit cell division during development. Development. 2000 Dec;127(23):5071–5082. [PubMed]
  • Kodoyianni V, Maine EM, 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. [PMC free article] [PubMed]
  • Kraemer B, Crittenden S, Gallegos M, Moulder G, Barstead R, Kimble J, Wickens M. NANOS-3 and FBF proteins physically interact to control the sperm-oocyte switch in Caenorhabditis elegans. Curr Biol. 1999 Sep 23;9(18):1009–1018. [PubMed]
  • Lai Eric C. Keeping a good pathway down: transcriptional repression of Notch pathway target genes by CSL proteins. EMBO Rep. 2002 Sep;3(9):840–845. [PMC free article] [PubMed]
  • Lee MH, Schedl T. Identification of in vivo mRNA targets of GLD-1, a maxi-KH motif containing protein required for C. elegans germ cell development. Genes Dev. 2001 Sep 15;15(18):2408–2420. [PMC free article] [PubMed]
  • Lin Haifan. The stem-cell niche theory: lessons from flies. Nat Rev Genet. 2002 Dec;3(12):931–940. [PubMed]
  • Lin H, Spradling AC. A novel group of pumilio mutations affects the asymmetric division of germline stem cells in the Drosophila ovary. Development. 1997 Jun;124(12):2463–2476. [PubMed]
  • Marin Veronica A, Evans Thomas C. Translational repression of a C. elegans Notch mRNA by the STAR/KH domain protein GLD-1. Development. 2003 Jun;130(12):2623–2632. [PubMed]
  • Marshman Emma, Booth Catherine, Potten Christopher S. The intestinal epithelial stem cell. Bioessays. 2002 Jan;24(1):91–98. [PubMed]
  • Moore Frederick L, Jaruzelska Jadwiga, Fox Mark S, Urano Jun, Firpo Meri T, Turek Paul J, Dorfman David M, Pera Renee A Reijo. Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-like proteins. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):538–543. [PMC free article] [PubMed]
  • Petcherski AG, Kimble J. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature. 2000 May 18;405(6784):364–368. [PubMed]
  • Petcherski AG, Kimble J. Mastermind is a putative activator for Notch. Curr Biol. 2000 Jun 29;10(13):R471–R473. [PubMed]
  • Souza GM, da Silva AM, Kuspa A. Starvation promotes Dictyostelium development by relieving PufA inhibition of PKA translation through the YakA kinase pathway. Development. 1999 Jun;126(14):3263–3274. [PubMed]
  • Varnum-Finney B, Xu L, Brashem-Stein C, Nourigat C, Flowers D, Bakkour S, Pear WS, Bernstein ID. Pluripotent, cytokine-dependent, hematopoietic stem cells are immortalized by constitutive Notch1 signaling. Nat Med. 2000 Nov;6(11):1278–1281. [PubMed]
  • Wang Liaoteng, Eckmann Christian R, Kadyk Lisa C, Wickens Marvin, Kimble Judith. A regulatory cytoplasmic poly(A) polymerase in Caenorhabditis elegans. Nature. 2002 Sep 19;419(6904):312–316. [PubMed]
  • Watt FM, Hogan BL. Out of Eden: stem cells and their niches. Science. 2000 Feb 25;287(5457):1427–1430. [PubMed]
  • Zhang B, Gallegos M, Puoti A, Durkin E, Fields S, Kimble J, Wickens MP. A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature. 1997 Dec 4;390(6659):477–484. [PubMed]

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