Using Caenorhabditis to Explore the Evolution of the Germ Line

  • Eric S. HaagEmail author
  • Qinwen Liu
Part of the Advances in Experimental Medicine and Biology book series (volume 757)


Germ cells share core attributes and homologous molecular components across animal phyla. Nevertheless, abrupt shifts in reproductive mode often occur that are mediated by the rapid evolution of germ cell properties. Studies of Caenorhabditis nematodes show how the otherwise conserved RNA-binding proteins (RBPs) that regulate germline development and differentiation can undergo surprisingly rapid functional evolution. This occurs even as the narrow biochemical tasks performed by the RBPs remain constant. The biological roles of germline RBPs are thus highly context-dependent, and the inference of archetypal roles from isolated models in different phyla may therefore be premature.


RNA-binding protein Translation PUF proteins GLD-1 



We thank the community of Caenorhabditis researchers for fostering a collegial and collaborative research culture, and the National Institutes of Health and National Science Foundation for research funding.


  1. Ahringer J, Kimble J (1991) Control of the sperm-oocyte switch in Caenorhabditis elegans hermaphrodites by the fem-3 3’ untranslated region. Nature 349(6307):346–348PubMedGoogle Scholar
  2. Ariz M, Mainpal R, Subramaniam K (2009) C. elegans RNA-binding proteins PUF-8 and MEX-3 function redundantly to promote germline stem cell mitosis. Dev Biol 326(2):295–304PubMedGoogle Scholar
  3. Austin J, Kimble J (1989) Transcript analysis of glp-1 and lin-12, homologous genes required for cell interactions during development of C. elegans. Cell 58(3):565–571. doi:0092-8674(89)90437-6[pii] PubMedGoogle Scholar
  4. Baldi C, Cho S, Ellis RE (2009) Mutations in two independent pathways are sufficient to create hermaphroditic nematodes. Science 326(5955):1002–1005. doi:326/5955/1002[pii]10.1126/science.1176013 PubMedGoogle Scholar
  5. Barton MK, Schedl TB, Kimble J (1987) Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans. Genetics 115(1):107–119PubMedGoogle Scholar
  6. Beadell AV, Liu Q, Johnson DM, Haag ES (2011) Independent recruitments of a translational regulator in the evolution of self-fertile nematodes. Proc Natl Acad Sci USA 108:19672–19677. doi:10.1073/pnas.1108068108 PubMedGoogle Scholar
  7. Beer J, Technau GM, Campos-Ortega JA (1987) Lineage analysis of transplanted individual cells in embryos of Drosophila melanogaster. Dev Genes Evol 196(4):222–230. doi:10.1007/bf00376346 Google Scholar
  8. Berry LW, Westlund B, Schedl T (1997) Germ-line tumor formation caused by activation of glp-1, a Caenorhabditis elegans member of the Notch family of receptors. Development 124(4):925–936PubMedGoogle Scholar
  9. Boterenbrood EC, Nieuwkoop PD (1973) The formation of the mesoderm in urodelean amphibians. Dev Genes Evol 173(4):319–332. doi:10.1007/bf00575837 Google Scholar
  10. Brangwynne CP, Eckmann CR, Courson DS, Rybarska A, Hoege C, Gharakhani J, Julicher F, Hyman AA (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324(5935):1729–1732PubMedGoogle Scholar
  11. Brawley C, Matunis E (2004) Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivo. Science 304(5675):1331–1334. doi:10.1126/science.1097676 PubMedGoogle Scholar
  12. Carroll SB (2008) Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell 134(1):25–36PubMedGoogle Scholar
  13. Chen P, Ellis RE (2000) TRA-1A regulates transcription of fog-3, which controls germ cell fate in C. elegans. Development 127(14):3119–3129PubMedGoogle Scholar
  14. Chen PJ, Cho S et al (2001) Specification of germ cell fates by FOG-3 has been conserved during nematode evolution. Genetics 158(4):1513–1525PubMedGoogle Scholar
  15. Cho S, Jin SW, Cohen A, Ellis RE (2004) A phylogeny of Caenorhabditis reveals frequent loss of introns during nematode evolution. Genome Res 14(7):1207–1220PubMedGoogle Scholar
  16. Cinquin O, Crittenden SL, Morgan DE, Kimble J (2010) Progression from a stem cell-like state to early differentiation in the C. elegans germ line. Proc Natl Acad Sci USA 107(5):2048–2053. doi:0912704107[pii]10.1073/pnas.0912704107 PubMedGoogle Scholar
  17. Clifford R, Lee MH, Nayak S, Ohmachi M, Giorgini F, Schedl T (2000) FOG-2, a novel F-box containing protein, associates with the GLD-1 RNA binding protein and directs male sex determination in the C. elegans hermaphrodite germline. Development 127(24):5265–5276PubMedGoogle Scholar
  18. Coward SJ (1974) Chromatoid bodies in somatic cells of the planarian: observations on their behavior during mitosis. Anat Rec 180(3):533–545. doi:10.1002/ar.1091800312 PubMedGoogle Scholar
  19. Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H (1998) A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. Genes Dev 12(23):3715–3727PubMedGoogle Scholar
  20. Crittenden SL, Troemel ER, Evans TC, Kimble J (1994) GLP-1 is localized to the mitotic region of the C. elegans germ line. Development 120(10):2901–2911PubMedGoogle Scholar
  21. Crittenden SL, Bernstein DS, Bachorik JL, Thompson BE, Gallegos M, Petcherski AG, Moulder G, Barstead R, Wickens M, Kimble J (2002) A conserved RNA-binding protein controls germline stem cells in Caenorhabditis elegans. Nature 417(6889):660–663. doi:10.1038/nature754 PubMedGoogle Scholar
  22. Crittenden SL, Leonhard KA, Byrd DT, Kimble J (2006) Cellular analyses of the mitotic region in the Caenorhabditis elegans adult germ line. Mol Biol Cell 17(7):3051–3061. doi:E06-03-0170[pii]10.1091/mbc.E06-03-0170 PubMedGoogle Scholar
  23. Cutter AD, Felix MA, Barriere A, Charlesworth D (2006) Patterns of nucleotide polymorphism distinguish temperate and tropical wild isolates of Caenorhabditis briggsae. Genetics 173(4):2021–2031PubMedGoogle Scholar
  24. de Bono M, Hodgkin J (1996) Evolution of sex determination in Caenorhabditis: unusually high divergence of tra-1 and its functional consequences. Genetics 144:587–595PubMedGoogle Scholar
  25. de Rooij DG (2009) The spermatogonial stem cell niche. Microsc Res Tech 72(8):580–585. doi:10.1002/jemt.20699 PubMedGoogle Scholar
  26. Dolgin ES, Felix MA, Cutter AD (2008) Hakuna Nematoda: genetic and phenotypic diversity in African isolates of Caenorhabditis elegans and C. briggsae. Heredity 100(3):304–315PubMedGoogle Scholar
  27. Ellis RE (2008) Sex determination in the Caenorhabditis elegans germ line. Curr Top Dev Biol 83:41–64PubMedGoogle Scholar
  28. Extavour CG (2007) Evolution of the bilaterian germ line: lineage origin and modulation of specification mechanisms. Integr Comp Biol 47(5):770–785PubMedGoogle Scholar
  29. Extavour CG, Akam M (2003) Mechanisms of germ cell specification across the metazoans: epigenesis and preformation. Development 130(24):5869–5884PubMedGoogle Scholar
  30. Francis R, Maine E, Schedl T (1995) Analysis of the multiple roles of gld-1 in germline development: interactions with the sex determination cascade and the glp-1 signaling pathway. Genetics 139(2):607–630PubMedGoogle Scholar
  31. Gallegos M, Ahringer J, Crittenden S, Kimble J (1998) Repression by the 3’ UTR of fem-3, a sex-determining gene, relies on a ubiquitous mog-dependent control in Caenorhabditis elegans. EMBO J 17(21):6337–6347PubMedGoogle Scholar
  32. Gallo CM, Wang JT, Motegi F, Seydoux G (2010) Cytoplasmic partitioning of P granule components is not required to specify the germline in C. elegans. Science 330(6011):1685–1689PubMedGoogle Scholar
  33. Gonczy P, DiNardo S (1996) The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis. Development 122(8):2437–2447PubMedGoogle Scholar
  34. Goodenough U, Lin H, Lee JH (2007) Sex determination in Chlamydomonas. Semin Cell Dev Biol 18(3):350–361PubMedGoogle Scholar
  35. Goodwin EB, Okkema PG, Evans TC, Kimble J (1993) Translational regulation of tra-2 by its 3’ untranslated region controls sexual identity in C. elegans. Cell 75(2):329–339PubMedGoogle Scholar
  36. Goriely A, McVean GA et al (2005) Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia. Proc Natl Acad Sci USA 102(17):6051–6056PubMedGoogle Scholar
  37. Graustein A, Gaspar JM, Walters JR, Palopoli MF (2002) Levels of DNA polymorphism vary with mating system in the nematode genus Caenorhabditis. Genetics 161(1):99–107PubMedGoogle Scholar
  38. Guo T, Peters AH, Newmark PA (2006) A Bruno-like gene is required for stem cell maintenance in planarians. Dev Cell 11(2):159–169. doi:S1534-5807(06)00260-7[pii]10.1016/j.devcel.2006.06.004 PubMedGoogle Scholar
  39. Guo Y, Lang S, Ellis RE (2009) Independent recruitment of F box genes to regulate hermaphrodite development during nematode evolution. Curr Biol 19(21):1853–1860PubMedGoogle Scholar
  40. Haag ES (2007) Why two sexes? Sex determination in multicellular organisms and protistan mating types. Semin Cell Dev Biol 18(3):348–349PubMedGoogle Scholar
  41. Haag ES, Kimble J (2000) 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 155(1):105–116PubMedGoogle Scholar
  42. Haag ES, Wang S, Kimble J (2002) Rapid coevolution of the nematode sex-determining genes fem-3 and tra-2. Curr Biol 12(23):2035–2041PubMedGoogle Scholar
  43. Handberg-Thorsager M, Salo E (2007) The planarian nanos-like gene Smednos is expressed in germline and eye precursor cells during development and regeneration. Dev Genes Evol 217(5):403–411. doi:10.1007/s00427-007-0146-3 PubMedGoogle Scholar
  44. Hansen D, Pilgrim D (1998) Molecular evolution of a sex determination protein. FEM-2 (pp 2c) in Caenorhabditis. Genetics 149:1353–1362PubMedGoogle Scholar
  45. Hansen D, Wilson-Berry L, Dang T, Schedl T (2004) Control of the proliferation versus meiotic development decision in the C. elegans germline through regulation of GLD-1 protein accumulation. Development 131:93–104PubMedGoogle Scholar
  46. Hanyu-Nakamura K, Sonobe-Nojima H, Tanigawa A, Lasko P, Nakamura A (2008) Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells. Nature 451(7179):730–733. doi:nature06498[pii]10.1038/nature06498 PubMedGoogle Scholar
  47. Hashimoto Y, Maegawa S, Nagai T, Yamaha E, Suzuki H, Yasuda K, Inoue K (2004) Localized maternal factors are required for zebrafish germ cell formation. Dev Biol 268(1):152–161. doi:10.1016/j.ydbio.2003.12.013 S0012160603007942[pii] PubMedGoogle Scholar
  48. Heasman J, Quarmby J, Wylie CC (1984) The mitochondrial cloud of Xenopus oocytes: the source of germinal granule material. Dev Biol 105(2):458–469. doi:0012-1606(84)90303-8[pii] PubMedGoogle Scholar
  49. Heffer A, Shultz JW, Pick L (2010) Surprising flexibility in a conserved Hox transcription factor over 550 million years of evolution. Proc Natl Acad Sci USA 107(42):18040–18045PubMedGoogle Scholar
  50. Henderson ST, Gao D, Lambie EJ, Kimble J (1994) lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans. Development 120(10):2913–2924PubMedGoogle Scholar
  51. Hill RC, Haag ES (2009) A sensitized genetic background reveals evolution near the terminus of the Caenorhabditis germline sex determination pathway. Evol Dev 4:333–341Google Scholar
  52. Hill RC, de Carvalho CE, Salogiannis J, Schlager B, Pilgrim D, Haag ES (2006) Genetic flexibility in the convergent evolution of hermaphroditism in Caenorhabditis nematodes. Dev Cell 10(4):531–538PubMedGoogle Scholar
  53. Hillier LW, Miller RD, Baird SE, Chinwalla A, Fulton LA, Koboldt DC, Waterston RH (2007) Comparison of C. elegans and C. briggsae genome sequences reveals extensive conservation of chromosome organization and synteny. PLoS Biol 5(7):e167PubMedGoogle Scholar
  54. Hird SN, Paulsen JE, Strome S (1996) Segregation of germ granules in living Caenorhabditis elegans embryos: cell-type-specific mechanisms for cytoplasmic localisation. Development 122(4):1303–1312PubMedGoogle Scholar
  55. Hodgkin J (1986) Sex determination in the nematode C. elegans: analysis of tra-3 suppressors and characterization of fem genes. Genetics 114(1):15–52PubMedGoogle Scholar
  56. Hori I, Kishida Y (2003) Quantitative changes in nuclear pores and chromatoid bodies induced by neuropeptides during cell differentiation in the planarian Dugesia japonica. J Submicrosc Cytol Pathol 35(4):439–444PubMedGoogle Scholar
  57. Huettner AF (1923) The origin of the germ cells in Drosophila melanogaster. J Morphol 37(2):385–423. doi:10.1002/jmor.1050370204 Google Scholar
  58. Humphrey RR (1925) The primordial germ cells of Hemidactylium and other amphibia. J Morphol 41(1):1–43. doi:10.1002/jmor.1050410103 Google Scholar
  59. Humphrey RR (1927) Extirpation of the primordial germ cells of Amblystoma: its effect upon the development of the gonad. J Exp Zool 49(2):363–399. doi:10.1002/jez.1400490207 Google Scholar
  60. Ikenishi K, Nieuwkoop PD (1978) Location and ultrastructure of primordial germ cells (PGCs) in Ambystoma mexicanum. Dev Growth Differ 20(1):1–9. doi:10.1111/j.1440-169X.1978.00001.x Google Scholar
  61. Illmensee K, Mahowald AP (1974) Transplantation of posterior polar plasm in Drosophila. Induction of germ cells at the anterior pole of the egg. Proc Natl Acad Sci USA 71(4):1016–1020PubMedGoogle Scholar
  62. Jan E, Yoon JW, Walterhouse D, Iannaccone P, Goodwin EB (1997) Conservation of the C. elegans tra-2 3’UTR translational control. EMBO J 16(20):6301–6313PubMedGoogle Scholar
  63. Jan E, Motzny CK, Graves LE, Goodwin EB (1999) The STAR protein, GLD-1, is a translational regulator of sexual identity in Caenorhabditis elegans. EMBO J 18(1):258–269. doi:10.1093/emboj/18.1.258 PubMedGoogle Scholar
  64. Johnson AD, Bachvarova RF, Drum M, Masi T (2001) Expression of axolotl DAZL RNA, a marker of germ plasm: widespread maternal RNA and onset of expression in germ cells approaching the gonad. Dev Biol 234(2):402–415. doi:10.1006/dbio.2001.0264 S0012-1606(01)90264-7[pii] PubMedGoogle Scholar
  65. Johnson AD, Crother B, White ME, Patient R, Bachvarova RF, Drum M, Masi T (2003) Regulative germ cell specification in axolotl embryos: a primitive trait conserved in the mammalian lineage. Philos Trans R Soc Lond B Biol Sci 358(1436):1371–1379. doi:10.1098/rstb.2003.1331 PubMedGoogle Scholar
  66. Jones AR, Francis R, Schedl T (1996) GLD-1, a cytoplasmic protein essential for oocyte ­differentiation, shows stage- and sex-specific expression during Caenorhabditis elegans germline development. Dev Biol 180(1):165–183. doi:S0012-1606(96)90293-6[pii]10.1006/dbio.1996.0293 PubMedGoogle Scholar
  67. Kawase E, Wong MD, Ding BC, Xie T (2004) Gbb/Bmp signaling is essential for maintaining germline stem cells and for repressing bam transcription in the Drosophila testis. Development 131(6):1365–1375. doi:10.1242/dev.01025 dev.01025[pii] PubMedGoogle Scholar
  68. Kelleher DF, de Carvalho CE, Doty AV, Layton M, Cheng AT, Mathies LD, Pilgrim D, Haag ES (2008) Comparative genetics of sex determination: masculinizing mutations in Caenorhabditis briggsae. Genetics 178(3):1415–1429PubMedGoogle Scholar
  69. Kershner AM, Kimble J (2010) Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator. Proc Natl Acad Sci USA 107(8):3936–3941. doi:1000495107[pii]10.1073/pnas.1000495107 PubMedGoogle Scholar
  70. Kimble J, Crittenden SL (2007) Controls of germline stem cells, entry into meiosis, and the sperm/oocyte decision in Caenorhabditis elegans. Annu Rev Cell Dev Biol 23:405–433. doi:10.1146/annurev.cellbio.23.090506.123326 PubMedGoogle Scholar
  71. Kimble J, Simpson P (1997) The LIN-12/Notch signaling pathway and its regulation. Annu Rev Cell Dev Biol 13:333–361. doi:10.1146/annurev.cellbio.13.1.333 PubMedGoogle Scholar
  72. Kimble JE, White JG (1981) On the control of germ cell development in Caenorhabditis elegans. Dev Biol 81(2):208–219. doi:0012-1606(81)90284-0[pii] PubMedGoogle Scholar
  73. King FJ, Lin H (1999) Somatic signaling mediated by fs(1)Yb is essential for germline stem cell maintenance during Drosophila oogenesis. Development 126(9):1833–1844PubMedGoogle Scholar
  74. Kiontke K, Sudhaus W (2006) Ecology of Caenorhabditis species. WormBook:1–14. doi:10.1895/wormbook.1.37.1Google Scholar
  75. Kiontke K, Gavin NP, Raynes Y, Roehrig C, Piano F, Fitch DHA (2004) Caenorhabditis phylogeny predicts convergence of hermaphroditism and extensive intron loss. Proc Natl Acad Sci USA 101(24):9003–9008PubMedGoogle Scholar
  76. Kiontke K, Félix M-A, Ailion M, Rockman M, Braendle C, Penigault J-B, Fitch DHA (2011) A phylogeny and molecular barcodes for Caenorhabditis, with numerous new species from rotting fruits. BMC Evol Biol 11:339. doi:10.1186/1471-2148-11-339 PubMedGoogle Scholar
  77. Kirilly D, Xie T (2007) The Drosophila ovary: an active stem cell community. Cell Res 17(1):15–25. doi:7310123[pii]10.1038/ PubMedGoogle Scholar
  78. Koboldt DC, Staisch J, Thillainathan B, Haines K, Baird SE, Chamberlin HM, Haag ES, Miller RD, Gupta BP (2010) A toolkit for rapid gene mapping in the nematode Caenorhabditis briggsae. BMC Genomics 11:236. doi:1471-2164-11-236[pii]10.1186/1471-2164-11-236 PubMedGoogle Scholar
  79. Komiya T, Itoh K, Ikenishi K, Furusawa M (1994) Isolation and characterization of a novel gene of the DEAD box protein family which is specifically expressed in germ cells of Xenopus laevis. Dev Biol 162(2):354–363. doi:10.1006/dbio.1994.1093 S0012-1606(84)71093-1[pii] PubMedGoogle Scholar
  80. Kraemer B, Crittenden S, Gallegos M, Moulder G, Barstead R, Kimble J, Wickens M (1999) NANOS-3 and FBF proteins physically interact to control the sperm-oocyte switch in Caenorhabditis elegans. Curr Biol 9(18):1009–1018PubMedGoogle Scholar
  81. Kurimoto K, Yabuta Y, Ohinata Y, Shigeta M, Yamanaka K, Saitou M (2008) Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice. Genes Dev 22(12):1617–1635. doi:22/12/1617[pii]10.1101/gad.1649908 PubMedGoogle Scholar
  82. Kuwabara PE (1996) Interspecies comparison reveals evolution of control regions in the nematode sex-determining gene tra-2. Genetics 144(2):597–607PubMedGoogle Scholar
  83. Lamont LB, Crittenden SL, Bernstein D, Wickens M, Kimble J (2004) FBF-1 and FBF-2 regulate the size of the mitotic region in the C. elegans germline. Dev Cell 7(5):697–707. doi:S1534580704003338[pii]10.1016/j.devcel.2004.09.013 PubMedGoogle Scholar
  84. Lawson KA, Dunn NR, Roelen BA, Zeinstra LM, Davis AM, Wright CV, Korving JP, Hogan BL (1999) Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 13(4):424–436PubMedGoogle Scholar
  85. Lee MH, Schedl T (2001) Identification of in vivo mRNA targets of GLD-1, a maxi-KH motif containing protein required for C. elegans germ cell development. Genes Dev 15(18):2408–2420. doi:10.1101/gad.915901 PubMedGoogle Scholar
  86. Lee MH, Schedl T (2010) C. elegans star proteins, GLD-1 and ASD-2, regulate specific RNA targets to control development. Advances in Experimental Medicine and Biology 693:106–122PubMedGoogle Scholar
  87. Lee SC, Ni M, Li W, Shertz C, Heitman J (2010) The evolution of sex: a perspective from the fungal kingdom. Microbiol Mol Biol Rev 74(2):298–340. doi:74/2/298[pii]10.1128/MMBR.00005-10 PubMedGoogle Scholar
  88. Leonard J (2010) The evolution of sexes, anisogamy, and sexual systems: natural versus sexual selection. In: Leonard J, Cordoba-Aguilar A (eds) The evolution of primary sexual characters in animals. Oxford University Press, OxfordGoogle Scholar
  89. Lin H (2002) The stem-cell niche theory: lessons from flies. Nat Rev Genet 3(12):931–940. doi:10.1038/nrg952 nrg952[pii] PubMedGoogle Scholar
  90. Liu Q, Stumpf C, Wickens M, Haag ES (2012) Context-dependent function of a conserved translational regulatory module. Development 139:ppTBAGoogle Scholar
  91. Lublin AL, Evans TC (2007) The RNA-binding proteins PUF-5, PUF-6, and PUF-7 reveal multiple systems for maternal mRNA regulation during C. elegans oogenesis. Dev Biol 303(2):635–649PubMedGoogle Scholar
  92. Mann RS, Lelli KM, Joshi R (2009) Hox specificity unique roles for cofactors and collaborators. Curr Top Dev Biol 88:63–101PubMedGoogle Scholar
  93. McCarter J, Bartlett B, Dang T, Schedl T (1997) Soma-germ cell interactions in Caenorhabditis elegans: multiple events of hermaphrodite germline development require the somatic sheath and spermathecal lineages. Dev Biol 181(2):121–143. doi:10.1006/dbio.1996.8429 S0012-1606(96)98429-8[pii] PubMedGoogle Scholar
  94. McCourt RM, Delwiche CF, Karol KG (2004) Charophyte algae and land plant origins. Trends Ecol Evol 19(12):661–666PubMedGoogle Scholar
  95. McGovern M, Voutev R, Maciejowski J, Corsi AK, Hubbard EJ (2009) A “latent niche” mechanism for tumor initiation. Proc Natl Acad Sci USA 106(28):11617–11622. doi:0903768106[pii]10.1073/pnas.0903768106 PubMedGoogle Scholar
  96. Mello CC, Draper BW, Krause M, Weintraub H, Priess JR (1992) The pie-1 and mex-1 genes and maternal control of blastomere identity in early C. elegans embryos. Cell 70(1):163–176. doi:0092-8674(92)90542-K[pii] PubMedGoogle Scholar
  97. Mello CC, Schubert C, Draper B, Zhang W, Lobel R, Priess JR (1996) The PIE-1 protein and germline specification in C. elegans embryos. Nature 382(6593):710–712. doi:10.1038/382710a0 PubMedGoogle Scholar
  98. Meng X, Lindahl M, Hyvonen ME, Parvinen M, de Rooij DG, Hess MW, Raatikainen-Ahokas A, Sainio K, Rauvala H, Lakso M, Pichel JG, Westphal H, Saarma M, Sariola H (2000) Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 287(5457):1489–1493. doi:8297[pii] PubMedGoogle Scholar
  99. Merritt C, Seydoux G (2010) The Puf RNA-binding proteins FBF-1 and FBF-2 inhibit the expression of synaptonemal complex proteins in germline stem cells. Development 137(11):1787–1798. doi:dev.050799[pii]10.1242/dev.050799 PubMedGoogle Scholar
  100. Merritt C, Rasoloson D, Ko D, Seydoux G (2008) 3’ UTRs are the primary regulators of gene expression in the C. elegans germline. Curr Biol 18(19):1476–1482PubMedGoogle Scholar
  101. Morgan T (1901) Growth and regeneration in Planaria lugubris. Dev Genes Evol 13(1):179–212. doi:10.1007/bf02161982 Google Scholar
  102. Morgan CT, Lee M-H et al (2010) Chemical reprogramming of Caenorhabditis elegans germ cell fate. Nat Chem Biol 6(2):102–104PubMedGoogle Scholar
  103. Nayak S, Goree J, Schedl T (2005) fog-2 and the evolution of self-fertile hermaphroditism in Caenorhabditis. PLoS Biol 3(1):e6PubMedGoogle Scholar
  104. Newmark PA, Sanchez Alvarado A (2002) Not your father’s planarian: a classic model enters the era of functional genomics. Nat Rev Genet 3(3):210–219. doi:10.1038/nrg759 nrg759[pii] PubMedGoogle Scholar
  105. Olsen LC, Aasland R, Fjose A (1997) A vasa-like gene in zebrafish identifies putative primordial germ cells. Mech Dev 66(1–2):95–105PubMedGoogle Scholar
  106. Otori M, Karashima T, Yamamoto M (2006) The Caenorhabditis elegans homologue of deleted in azoospermia is involved in the sperm/oocyte switch. Mol Biol Cell 17(7):3147–3155. doi:E05-11-1067[pii]10.1091/mbc.E05-11-1067 PubMedGoogle Scholar
  107. Pepper AS, Killian DJ, Hubbard EJ (2003a) Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition. Genetics 163(1):115–132PubMedGoogle Scholar
  108. Pepper AS, Lo TW, Killian DJ, Hall DH, Hubbard EJ (2003b) The establishment of Caenorhabditis elegans germline pattern is controlled by overlapping proximal and distal somatic gonad signals. Dev Biol 259(2):336–350. doi:S0012160603002033[pii] PubMedGoogle Scholar
  109. Praitis V, Casey E, Collar D, Austin J (2001) Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. Genetics 157(3):1217–1226PubMedGoogle Scholar
  110. Ramesh MA, Malik SB, Logsdon JM Jr (2005) A phylogenomic inventory of meiotic genes; ­evidence for sex in Giardia and an early eukaryotic origin of meiosis. Curr Biol 15(2):185–191PubMedGoogle Scholar
  111. Raz E (2003) Primordial germ-cell development: the zebrafish perspective. Nat Rev Genet 4(9):690–700. doi:10.1038/nrg1154 PubMedGoogle Scholar
  112. Reddien PW, Sanchez Alvarado A (2004) Fundamentals of planarian regeneration. Annu Rev Cell Dev Biol 20:725–757. doi:10.1146/annurev.cellbio.20.010403.095114 PubMedGoogle Scholar
  113. Ross JA, Koboldt DC, Staisch JE, Chamberlin HM, Gupta BP, Miller RD, Baird SE, Haag ES (2011) Caenorhabditis briggsae recombinant inbred line genotypes reveal inter-strain incompatibility and the evolution of recombination. PLoS Genet 7(7):e1002174PubMedGoogle Scholar
  114. Salo E, Baguna J (1984) Regeneration and pattern formation in planarians. I. The pattern of mitosis in anterior and posterior regeneration in Dugesia (G) tigrina, and a new proposal for blastema formation. J Embryol Exp Morphol 83:63–80PubMedGoogle Scholar
  115. Salvetti A, Rossi L, Lena A, Batistoni R, Deri P, Rainaldi G, Locci MT, Evangelista M, Gremigni V (2005) DjPum, a homologue of Drosophila Pumilio, is essential to planarian stem cell maintenance. Development 132(8):1863–1874. doi:dev.01785[pii]10.1242/dev.01785 PubMedGoogle Scholar
  116. Sanchez Alvarado A (2006) Planarian regeneration: its end is its beginning. Cell 124(2):241–245. doi:S0092-8674(06)00060-2[pii]10.1016/j.cell.2006.01.012 PubMedGoogle Scholar
  117. Sato K, Sugita T, Kobayashi K, Fujita K, Fujii T, Matsumoto Y, Mikami T, Nishizuka N, Nishizuka S, Shojima K, Suda M, Takahashi G, Himeno H, Muto A, Ishida S (2001) Localization of mitochondrial ribosomal RNA on the chromatoid bodies of marine planarian polyclad embryos. Dev Growth Differ 43(2):107–114. doi:dgd558[pii] PubMedGoogle Scholar
  118. Sato K, Shibata N, Orii H, Amikura R, Sakurai T, Agata K, Kobayashi S, Watanabe K (2006) Identification and origin of the germline stem cells as revealed by the expression of nanos-related gene in planarians. Dev Growth Differ 48(9):615–628. doi:DGD897[pii]10.1111/j.1440-169X.2006.00897.x PubMedGoogle Scholar
  119. Schedl T (1997) Developmental genetics of the germ line. doi:NBK20133 [bookaccession]Google Scholar
  120. Schedl T, Kimble J (1988) fog-2, a germ-line-specific sex determination gene required for hermaphrodite spermatogenesis in Caenorhabditis elegans. Genetics 119(1):43–61PubMedGoogle Scholar
  121. Schmid M, Kuchler B, Eckmann CR (2009) Two conserved regulatory cytoplasmic poly(A) polymerases, GLD-4 and GLD-2, regulate meiotic progression in C. elegans. Genes Dev 23(7):824–836. doi:23/7/824[pii]10.1101/gad.494009 PubMedGoogle Scholar
  122. Segal SP, Graves LE, Verheyden J, Goodwin EB (2001) RNA-Regulated TRA-1 nuclear export controls sexual fate. Dev Cell 1(4):539–551. doi:S1534-5807(01)00068-5[pii] PubMedGoogle Scholar
  123. Seydoux G, Mello CC, Pettitt J, Wood WB, Priess JR, Fire A (1996) Repression of gene expression in the embryonic germ lineage of C. elegans. Nature 382(6593):713–716. doi:10.1038/382713a0 PubMedGoogle Scholar
  124. Shibata N, Umesono Y, Orii H, Sakurai T, Watanabe K, Agata K (1999) Expression of vasa(vas)-related genes in germline cells and totipotent somatic stem cells of planarians. Dev Biol 206(1):73–87. doi:S0012-1606(98)99130-8[pii]10.1006/dbio.1998.9130 PubMedGoogle Scholar
  125. Shibata N, Rouhana L, Agata K (2010) Cellular and molecular dissection of pluripotent adult somatic stem cells in planarians. Dev Growth Differ 52(1):27–41. doi:DGD1155[pii]10.1111/j.1440-169X.2009.01155.x PubMedGoogle Scholar
  126. Song X, Xie T (2002) DE-cadherin-mediated cell adhesion is essential for maintaining somatic stem cells in the Drosophila ovary. Proc Natl Acad Sci USA 99(23):14813–14818. doi:10.1073/pnas.232389399 232389399[pii] PubMedGoogle Scholar
  127. Song X, Wong MD, Kawase E, Xi R, Ding BC, McCarthy JJ, Xie T (2004) Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary. Development 131(6):1353–1364. doi:10.1242/dev.01026 dev.01026[pii] PubMedGoogle Scholar
  128. Steenkamp ET, Wright J, Baldauf SL (2006) The protistan origins of animals and fungi. Mol Biol Evol 23(1):93–106. doi:msj011[pii]10.1093/molbev/msj011 PubMedGoogle Scholar
  129. Stein LD, Bao Z, Blasiar D, Blumenthal T, Brent MR, Chen N, Chinwalla A, Clarke L, Clee C, Coghlan A (2003) The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics. PLoS Biol 1(2):E45PubMedGoogle Scholar
  130. Stothard P, Pilgrim D (2006) Conspecific and interspecific interactions between the FEM-2 and the FEM-3 sex-determining proteins despite rapid sequence divergence. J Mol Evol 62(3):281–291PubMedGoogle Scholar
  131. Stothard P, Hansen D, Pilgrim D (2002) Evolution of the PP2C family in Caenorhabditis: rapid divergence of the sex-determining protein FEM-2. J Mol Evol 54(2):267–282PubMedGoogle Scholar
  132. Strome S, Wood WB (1983) Generation of asymmetry and segregation of germ-line granules in early C. elegans embryos. Cell 35(1):15–25PubMedGoogle Scholar
  133. Subramaniam K, Seydoux G (2003) Dedifferentiation of primary spermatocytes into germ cell tumors in C. elegans lacking the pumilio-like protein PUF-8. Curr Biol 13(2):134–139PubMedGoogle Scholar
  134. Suh N, Jedamzik B, Eckmann CR, Wickens M, Kimble J (2006) The GLD-2 poly(A) polymerase activates gld-1 mRNA in the Caenorhabditis elegans germ line. Proc Natl Acad Sci USA 103(41):15108–15112. doi:0607050103[pii]10.1073/pnas.0607050103 PubMedGoogle Scholar
  135. Sulston JE, Horvitz HR (1977) Post-embryonic cell lineages of the nematode Caenorhabditis elegans. Dev Biol 56(1):110–156. doi:0012-1606(77)90158-0[pii] PubMedGoogle Scholar
  136. Tam PP, Zhou SX (1996) The allocation of epiblast cells to ectodermal and germ-line lineages is influenced by the position of the cells in the gastrulating mouse embryo. Dev Biol 178(1):124–132. doi:S0012-1606(96)90203-1[pii]10.1006/dbio.1996.0203 PubMedGoogle Scholar
  137. Tanurdzic M, Banks JA (2004) Sex-determining mechanisms in land plants. Plant Cell 16(Suppl):S61–S71. doi:10.1105/tpc.016667 PubMedGoogle Scholar
  138. Tax FE, Yeargers JJ, Thomas JH (1994) Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila. Nature 368(6467):150–154. doi:10.1038/368150a0 PubMedGoogle Scholar
  139. Thompson BE, Bernstein DS, Bachorik JL, Petcherski AG, Wickens M, Kimble J (2005) Dose-dependent control of proliferation and sperm specification by FOG-1/CPEB. Development 132(15):3471–3481PubMedGoogle Scholar
  140. Timinszky G, Bortfeld M, Ladurner AG (2008) Repression of RNA polymerase II transcription by a Drosophila oligopeptide. PLoS One 3(6):e2506. doi:10.1371/journal.pone.0002506 PubMedGoogle Scholar
  141. Venkatarama T, Lai F, Luo X, Zhou Y, Newman K, King ML (2010) Repression of zygotic gene expression in the Xenopus germline. Development 137(4):651–660. doi:137/4/651[pii]10.1242/dev.038554 PubMedGoogle Scholar
  142. Wang S, Kimble J (2001) The TRA-1 transcription factor binds TRA-2 to regulate sexual fates in Caenorhabditis elegans. EMBO J 20(6):1363–1372. doi:10.1093/emboj/20.6.1363 PubMedGoogle Scholar
  143. Wang JT, Seydoux S (2012) Germ cell specification. Advances in Experimental Medicine and Biology 757:17–39. (Chap. 2, this volume) Springer, New YorkGoogle Scholar
  144. Wang Y, Zayas RM, Guo T, Newmark PA (2007) nanos function is essential for development and regeneration of planarian germ cells. Proc Natl Acad Sci USA 104(14):5901–5906. doi:0609708104[pii]10.1073/pnas.0609708104 PubMedGoogle Scholar
  145. Whitington PM, Dixon KE (1975) Quantitative studies of germ plasm and germ cells during early embryogenesis of Xenopus laevis. J Embryol Exp Morphol 33(1):57–74PubMedGoogle Scholar
  146. Wickens M, Bernstein DS, Kimble J, Parker R (2002) A PUF family portrait: 3’UTR regulation as a way of life. Trends Genet 18(3):150–157PubMedGoogle Scholar
  147. Williamson A, Lehmann R (1996) Germ cell development in Drosophila. Annu Rev Cell Dev Biol 12:365–391. doi:10.1146/annurev.cellbio.12.1.365 PubMedGoogle Scholar
  148. Wood WB, Laufer JS, Strome S (1982) Developmental determinants in embryos of Caenorhabditis elegans. J Nematol 14(2):267–273PubMedGoogle Scholar
  149. Woodruff GC, Eke O, Baird SE, Felix MA, Haag ES (2010) Insights into species divergence and the evolution of hermaphroditism from fertile interspecies hybrids of Caenorhabditis nematodes. Genetics 186(3):997–1012. doi:genetics.110.120550[pii]10.1534/genetics.110.120550 PubMedGoogle Scholar
  150. Wright JE, Gaidatzis D, Senften M, Farley BM, Westhof E, Ryder SP, Ciosk R (2010) A quantitative RNA code for mRNA target selection by the germline fate determinant GLD-1. EMBO J 30(3):533–545. doi:emboj2010334[pii]10.1038/emboj.2010.334 PubMedGoogle Scholar
  151. Wu H-R, Chen Y-T, Su Y-J, Holland L, Yu J-K (2011) Asymmetric localization of germline markers Vasa and Nanos during early development in the amphioxus Branchiostoma floridae. Dev Biol 353(147–59)Google Scholar
  152. Xie T, Li L (2007) Stem cells and their niche: an inseparable relationship. Development 134(11):2001–2006. doi:134/11/2001[pii]10.1242/dev.002022 PubMedGoogle Scholar
  153. Xie T, Spradling AC (2000) A niche maintaining germ line stem cells in the Drosophila ovary. Science 290(5490):328–330. doi:8892[pii] PubMedGoogle Scholar
  154. Ying Y, Zhao GQ (2001) Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Dev Biol 232(2):484–492. doi:10.1006/dbio.2001.0173 S0012-1606(01)90173-3[pii] PubMedGoogle Scholar
  155. Ying Y, Qi X, Zhao GQ (2001) Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways. Proc Natl Acad Sci USA 98(14):7858–7862. doi:10.1073/pnas.151242798 PubMedGoogle Scholar
  156. Yochem J, Greenwald I (1989) glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins. Cell 58(3):553–563. doi:0092-8674(89)90436-4[pii] PubMedGoogle Scholar
  157. Yoon C, Kawakami K, Hopkins N (1997) Zebrafish vasa homologue RNA is localized to the cleavage planes of 2- and 4-cell-stage embryos and is expressed in the primordial germ cells. Development 124(16):3157–3165PubMedGoogle Scholar
  158. Zanetti S, Puoti A (2012) Sex determination in the C. elegans germline. Advances in Experimental Medicine and Biology 757:41–69. (Chap. 3, this volume) Springer, New YorkGoogle Scholar
  159. Zarkower D (2006) Somatic sex determination. WormBook:1–12 (
  160. Zhang B, Gallegos M, Puoti A, Durkin E, Fields S, Kimble J, Wickens MP (1997) A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature 390(6659):477–484. doi:10.1038/37297 PubMedGoogle Scholar
  161. Zhao Z, Flibotte S, Murray JI, Blick D, Boyle TJ, Gupta B, Moerman DG, Waterston RH (2010) New tools for investigating the comparative biology of Caenorhabditis briggsae and C. elegans. Genetics 184(3):853–863. doi:genetics.109.110270[pii] PubMedGoogle Scholar
  162. Zhou Y, King ML (1996) Localization of Xcat-2 RNA, a putative germ plasm component, to the mitochondrial cloud in Xenopus stage I oocytes. Development 122:2947–2953PubMedGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of BiologyUniversity of MarylandCollege ParkUSA

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