Abstract
The germline of Caenorhabditis elegans derives from a single founder cell, the germline blastomere P4. P4 is the product of four asymmetric cleavages that divide the zygote into distinct somatic and germline (P) lineages. P4 inherits a specialized cytoplasm (“germ plasm”) containing maternally encoded proteins and RNAs. The germ plasm has been hypothesized to specify germ cell fate, but the mechanisms involved remain unclear. Three processes stand out: (1) inhibition of mRNA transcription to prevent activation of somatic development, (2) translational regulation of the nanos homolog nos-2 and of other germ plasm mRNAs, and (3) establishment of a unique, partially repressive chromatin. Together, these processes ensure that the daughters of P4, the primordial germ cells Z2 and Z3, gastrulate inside the embryo, associate with the somatic gonad, initiate the germline transcriptional program, and proliferate during larval development to generate ∼2,000 germ cells by adulthood.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Arata Y, Lee J-Y, Goldstein B, Sawa H (2010) Extracellular control of PAR protein localization during asymmetric cell division in the C. elegans embryo. Development 137:3337–3345. doi:10.1242/dev.054742
Barbee SA, Evans TC (2006) The Sm proteins regulate germ cell specification during early C. elegans embryogenesis. Dev Biol 291:132–143. doi:10.1016/j.ydbio.2005.12.011
Barbee SA, Lublin A, Evans TC (2002) A novel function for the Sm proteins in germ granule localization during C. elegans embryogenesis. Curr Biol 12:1502–1506
Batchelder C, Dunn MA, Choy B et al (1999) Transcriptional repression by the Caenorhabditis elegans germ-line protein PIE-1. Genes Dev 13:202–212
Baugh LR, Hill AA, Slonim DK et al (2003) Composition and dynamics of the Caenorhabditis elegans early embryonic transcriptome. Development 130:889–900. doi:10.1242/dev.00302
Bei Y, Hogan J, Berkowitz LA et al (2002) SRC-1 and Wnt signaling act together to specify endoderm and to control cleavage orientation in early C. elegans embryos. Dev cell 3:113–125
Bender L, Cao R, Zhang Y, Strome S (2004) The MES-2/MES-3/MES-6 complex and regulation of histone H3 methylation in C. elegans. Curr Biol 14:1639–1643. doi:10.1016/j
Bender LB, Suh J, Carroll CR et al (2006) MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line. Development 133:3907–3917. doi:10.1242/dev.02584
Berkowitz LA, Strome S (2000) MES-1, a protein required for unequal divisions of the germline in early C. elegans embryos, resembles receptor tyrosine kinases and is localized to the boundary between the germline and gut cells. Development 127:4419–4431
Bowerman B, Draper BW, Mello CC, Priess JR (1993) The maternal gene skn-1 encodes a protein that is distributed unequally in early C. elegans embryos. Cell 74:443–452
Boyd L, Guo S, Levitan D et al (1996) PAR-2 is asymmetrically distributed and promotes association of P granules and PAR-1 with the cortex in C. elegans embryos. Development 122:3075–3084
Brangwynne CP, Eckmann CR, Courson DS et al (2009) Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324:1729–1732. doi:10.1126/science.1172046
Brauchle M, Baumer K, Gönczy P (2003) Differential activation of the DNA replication checkpoint contributes to asynchrony of cell division in C. elegans embryos. Curr Biol 13:819–827. doi:10.1016/S
Budirahardja Y, Gönczy P (2008) PLK-1 asymmetry contributes to asynchronous cell division of C. elegans embryos. Development 135:1303–1313. doi:10.1242/dev.019075
Capowski EE, Martin P, Garvin C, Strome S (1991) Identification of grandchildless loci whose products are required for normal germ-line development in the nematode Caenorhabditis elegans. Genetics 129:1061–1072
Cheeks RJ, Canman JC, Gabriel WN et al (2004) C. elegans PAR proteins function by mobilizing and stabilizing asymmetrically localized protein complexes. Curr Biol 14:851–862. doi:10.1016/j
Cuenca AA, Schetter A, Aceto D et al (2003) Polarization of the C. elegans zygote proceeds via distinct establishment and maintenance phases. Development 130:1255–1265. doi:10.1242/dev.00284
D’Agostino I, Merritt C, Chen P-L et al (2006) Translational repression restricts expression of the C. elegans Nanos homolog NOS-2 to the embryonic germline. Dev Biol 292:244–252. doi:10.1016/j.ydbio.2005.11.046
Daniels BR, Perkins EM, Dobrowsky TM et al (2009) Asymmetric enrichment of PIE-1 in the Caenorhabditis elegans zygote mediated by binary counter diffusion. J Cell Biol 184:473–479. doi:10.1083/jcb.200809077
DeRenzo C, Reese KJ, Seydoux G (2003) Exclusion of germ plasm proteins from somatic lineages by cullin-dependent degradation. Nature 424:685–689. doi:10.1038/nature01887
Doniach T, Hodgkin J (1984) A sex-determining gene, fem-1, required for both male and hermaphrodite development in Caenorhabditis elegans. Dev Biol 106:223–235
Draper BW, Mello CC, Bowerman B et al (1996) MEX-3 is a KH domain protein that regulates blastomere identity in early C. elegans embryos. Cell 87:205–216
Encalada SE, Martin PR, Phillips JB et al (2000) DNA replication defects delay cell division and disrupt cell polarity in early Caenorhabditis elegans embryos. Dev Biol 228:225–238. doi:10.1006/dbio.2000.9965
Farley BM, Pagano JM, Ryder SP (2008) RNA target specificity of the embryonic cell fate determinant POS-1. RNA 14:2685–2697. doi:10.1261/rna.1256708
Fong Y, Bender L, Wang W, Strome S (2002) Regulation of the different chromatin states of autosomes and X chromosomes in the germ line of C. elegans. Science 296:2235–2238. doi:10.1126/science.1070790
Fukuyama M, Rougvie AE, Rothman JH (2006) C. elegans DAF-18/PTEN mediates nutrient-dependent arrest of cell cycle and growth in the germline. Curr Biol 16:773–779. doi:10.1016/j.cub.2006.02.073
Furuhashi H, Takasaki T, Rechtsteiner A et al (2010) Trans-generational epigenetic regulation of C. elegans primordial germ cells. Epigenetics chromatin 3:15. doi:10.1186/1756-8935-3-15
Gallo CM, Munro E, Rasoloson D et al (2008) Processing bodies and germ granules are distinct RNA granules that interact in C. elegans embryos. Dev Biol 323:76–87. doi:10.1016/j.ydbio.2008.07.008
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 330:1685–1689. doi:10.1126/science.1193697
Gerstein MB, Lu ZJ, Van Nostrand EL et al (2010) Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 330:1775–1787. doi:10.1126/science.1196914
Ghosh D, Seydoux G (2008) Inhibition of transcription by the Caenorhabditis elegans germline protein PIE-1: genetic evidence for distinct mechanisms targeting initiation and elongation. Genetics 178:235–243. doi:10.1534/genetics.107.083212
Gönczy P, Rose LS (2005) Asymmetric cell division and axis formation in the embryo. Wormbook, ed. The C elegans Research Community, Wormbook 1–20. doi: 10.1895/wormbook.1.30.1
Griffin EE, Odde DJ, Seydoux G (2011) Regulation of the MEX-5 gradient by a spatially segregated kinase/phosphatase cycle. Cell 146:955–968. doi:10.1016/j.cell.2011.08.012
Guedes S, Priess JR (1997) The C. elegans MEX-1 protein is present in germline blastomeres and is a P granule component. Development 124:731–739
Guo S, Kemphues K (1995) par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 81:611
Guven-Ozkan T, Nishi Y, Robertson SM, Lin R (2008) Global transcriptional repression in C. elegans germline precursors by regulated sequestration of TAF-4. Cell 135:149–160. doi:10.1016/j.cell.2008.07.040
Guven-Ozkan T, Robertson SM, Nishi Y, Lin R (2010) zif-1 translational repression defines a second, mutually exclusive OMA function in germline transcriptional repression. Development 137:3373–3382. doi:10.1242/dev.055327
Hanazawa M, Yonetani M, Sugimoto A (2011) PGL proteins self associate and bind RNPs to mediate germ granule assembly in C. elegans. J Cell Biol 192:929–937
Hanyu-Nakamura K, Sonobe-Nojima H, Tanigawa A et al (2008) Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells. Nature 451:730–733. doi:10.1038/nature06498
Harrell JR, Goldstein B (2011) Internalization of multiple cells during C. elegans gastrulation depends on common cytoskeletal mechanisms but different cell polarity and cell fate regulators. Dev Biol 350:1–12. doi:10.1016/j.ydbio.2010.09.012
Hird SN, Paulsen JE, Strome S (1996) Segregation of germ granules in living Caenorhabditis elegans embryos: cell-type-specific mechanisms for cytoplasmic localisation. Development 122:1303–1312
Jadhav S, Rana M, Subramaniam K (2008) Multiple maternal proteins coordinate to restrict the translation of C. elegans nanos-2 to primordial germ cells. Development 135:1803–1812. doi:10.1242/dev.013656
Johnson CL, Spence AM (2011) Epigenetic licensing of germline gene expression by maternal RNA in C. elegans. Science 333:1311–1314. doi:10.1126/science.1208178
Kapelle WS, Reinke V (2011) C. elegans meg-1 and meg-2 differentially interact with nanos family members to either promote or inhibit germ cell proliferation and survival. Genesis 49:380–391. doi:10.1002/dvg.20726
Kawasaki I, Shim YH, Kirchner J et al (1998) PGL-1, a predicted RNA-binding component of germ granules, is essential for fertility in C. elegans. Cell 94:635–645
Kawasaki I, Amiri A, Fan Y et al (2004) The PGL family proteins associate with germ granules and function redundantly in Caenorhabditis elegans germline development. Genetics 167:645–661. doi:10.1534/genetics.103.023093
Kemphues KJ, Priess JR, Morton DG, Cheng NS (1988) Identification of genes required for cytoplasmic localization in early C. elegans embryos. Cell 52:311–320
Kimble JE, White JG (1981) On the control of germ cell development in Caenorhabditis elegans. Dev Biol 81:208–219
Kumano G, Takatori N, Negishi T et al (2011) A maternal factor unique to ascidians silences the germline via binding to P-TEFb and RNAP II regulation. Curr Biol 21:1308–1313. doi:10.1016/j.cub.2011.06.050
Kuznicki KA, Smith PA, Leung-Chiu WM et al (2000) Combinatorial RNA interference indicates GLH-4 can compensate for GLH-1; these two P granule components are critical for fertility in C. elegans. Development 127:2907–2916
Leacock SW, Reinke V (2008) MEG-1 and MEG-2 are embryo-specific P-granule components required for germline development in Caenorhabditis elegans. Genetics 178:295–306. doi:10.1534/genetics.107.080218
Li W, DeBella LR, Guven-Ozkan T, Lin R, Rose LS (2009) An eIF4E-binding protein regulates katanin protein levels in C. elegans embryos. J Cell Biol 187:33–42
Mahowald A, Illmensee K (1974) Transplantation of posterior polar plasm in drosophila. Induction of germ cells at the anterior pole of the egg. PNAS 71:1016–1020
Mello CC, Draper BW, Weintraub H, Priess JF (1992) The pie-1 and mex-1 genes and maternal control of blastomere in early C. elegans embryos. Cell 70:163–176
Mello CC, Schubert C, Draper B et al (1996) The PIE-1 protein and germline specification in C. elegans embryos. Nature 382:710–712
Nakamura A, Seydoux G (2008) Less is more: specification of the germline by transcriptional repression. Development 135:3817–3827
Nishi Y, Lin R (2005) DYRK2 and GSK-3 phosphorylate and promote the timely degradation of OMA-1, a key regulator of the oocyte-to-embryo transition in C. elegans. Dev Biol 288:139–149. doi:10.1016/j.ydbio.2005.09.053
Nishi Y, Rogers E, Robertson SM, Lin R (2008) Polo kinases regulate C. elegans embryonic polarity via binding to DYRK2-primed MEX-5 and MEX-6. Development 135:687–697. doi:10.1242/dev.013425
Nousch M, Eckmann CR (2012) Translational control in the C. elegans germ line. Advances in Experimental Medicine and Biology 757:205–247. (Chap. 8, this volume) Springer, New York
Oldenbroek M, Robertson SM, Guven-Ozkan T et al (2012) Multiple RNA-binding proteins function combinatorially to control the soma-restricted expression pattern of the E3 ligase subunit ZIF-1. Dev Biol 363:388–398. doi:10.1016/j.ydbio.2012.01.002
Pagano JM, Farley BM, McCoig LM, Ryder SP (2007) Molecular basis of RNA recognition by the embryonic polarity determinant MEX-5. J Biol Chem 282:8883–8894. doi:10.1074/jbc.M700079200
Pagano JM, Farley BM, Essien KI, Ryder SP (2009) RNA recognition by the embryonic cell fate determinant and germline totipotency factor MEX-3. Proc Natl Acad Sci USA 106:20252–20257. doi:10.1073/pnas.0907916106
Parisi M, Lin H (2000) Translational repression: a duet of Nanos and Pumilio. Curr Biol 10:R81–R83
Paulsen JE, Capowski EE, Strome S (1995) Phenotypic and molecular analysis of mes-3, a maternal-effect gene required for proliferation and viability of the germ line in C. elegans. Genetics 141:1383–1398
Pellettieri J, Reinke V, Kim SK, Seydoux G (2003) Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. elegans. Dev Cell 5:451–462
Petrella LN, Wang W, Spike CA et al (2011) synMuv B proteins antagonize germline fate in the intestine and ensure C. elegans survival. Development 138:1069–1079. doi:10.1242/dev.059501
Rechtsteiner A, Ercan S, Takasaki T et al (2010) The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny. PLoS Genetics. doi:10.1371/journal.pgen.1001091
Reinke V (2006) Germline genomics. WormBook, ed. The C elegans Research Community, Wormbook 1–10. doi: 10.1895/wormbook.1.74.1
Rivers DM, Moreno S, Abraham M, Ahringer J (2008) PAR proteins direct asymmetry of the cell cycle regulators Polo-like kinase and Cdc25. J Cell Biol 180:877–885. doi:10.1083/jcb.200710018
Robertson S, Lin R (2012) The oocyte-to-embryo transition. Advances in Experimental Medicine and Biology 757:351–372. (Chap. 12, this volume) Springer, New York
Roussell DL, Bennett KL (1993) glh-1, a germ-line putative RNA helicase from Caenorhabditis, has four zinc fingers. Proc Natl Acad Sci USA 90:9300–9304
Schaner CE, Kelly WG (2006) Germline chromatin. Wormbook, ed. The C elegans Research Community, Wormbook 1–14. doi: 10.1895/wormbook.1.73.1
Schaner CE, Deshpande G, Schedl PD, Kelly WG (2003) A conserved chromatin architecture marks and maintains the restricted germ cell lineage in worms and flies. Dev Cell 5:747–757
Schierenberg E (1987) Reversal of cellular polarity and early cell-cell interaction in the embryo of Caenorhabditis elegans. Dev Biol 122:452–463. doi:10.1016/0012-1606(87)90309-5
Schierenberg E (1988) Localization and segregation of lineage-specific cleavage potential in embryos of Caenorhabditis elegans. Roux’s Arch Dev Biol 197:282–293
Schubert CM, Lin R, de Vries CJ et al (2000) MEX-5 and MEX-6 function to establish soma/germline asymmetry in early C. elegans embryos. Mol Cell 5:671–682
Seydoux G, Braun RE (2006) Pathway to totipotency: lessons from germ cells. Cell 127:891–904. doi:10.1016/j.cell.2006.11.016
Seydoux G, Dunn MA (1997) Transcriptionally repressed germ cells lack a subpopulation of phosphorylated RNA polymerase II in early embryos of Caenorhabditis elegans and Drosophila melanogaster. Development 124:2191–2201
Seydoux G, Fire A (1994) Soma-germline asymmetry in the distributions of embryonic RNAs in Caenorhabditis elegans. Development 120:2823–2834
Seydoux G, Mello CC, Pettitt J et al (1996) Repression of gene expression in the embryonic germ lineage of C. elegans. Nature 382:713–716
Shirae-Kurabayashi M, Matsuda K, Nakamura A (2011) Ci-Pem-1 localizes to the nucleus and represses somatic gene transcription in the germline of Ciona intestinalis embryos. Development 138:2871–2881. doi:10.1242/dev.058131
Shirayama M, Soto MC, Ishidate T et al (2006) The conserved kinases CDK-1, GSK-3, KIN-19, and MBK-2 promote OMA-1 destruction to regulate the oocyte-to-embryo transition in C. elegans. Curr Biol 16:47–55. doi:10.1016/j.cub.2005.11.070
Spencer WC, Zeller G, Watson JD et al (2011) A spatial and temporal map of C. elegans gene expression. Genome Res 21:325–341. doi:10.1101/gr.114595.110
Spike C, Meyer N, Racen E et al (2008) Genetic analysis of the Caenorhabditis elegans GLH family of P-granule proteins. Genetics 178:1973–1987. doi:10.1534/genetics.107.083469
Spilker AC, Rabilotta A, Zbinden C et al (2009) MAP kinase signaling antagonizes PAR-1 function during polarization of the early Caenorhabditis elegans embryo. Genetics 183:965–977. doi:10.1534/genetics.109.106716
Stitzel ML, Pellettieri J, Seydoux G (2006) The C. elegans DYRK kinase MBK-2 marks oocyte proteins for degradation in response to meiotic maturation. Curr Biol 16:56–62. doi:10.1016/j.cub.2005.11.063
Strome S (2005) Specification of the germ line. Wormbook, ed. The C elegans Research Community, Wormbook 1–10. doi: 10.1895/wormbook.1.9.1
Strome S, Lehmann R (1997) Germ versus soma decisions: lessons from flies and worms. Science 316:392–393. doi:10.1126/science.1140846
Strome S, Martin P, Schierenberg E, Paulsen J (1995) Transformation of the germ line into muscle in mes-1 mutant embryos of C. elegans. Development 121:2961–2972
Subramaniam K, Seydoux G (1999) nos-1 and nos-2, two genes related to Drosophila nanos, regulate primordial germ cell development and survival in Caenorhabditis elegans. Development 126:4861–4871
Sulston JE, Schierenberg E, White JG, Thomson JN (1983) The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol 100:64–119
Tabara H, Hill RJ, Mello CC et al (1999) pos-1 encodes a cytoplasmic zinc-finger protein essential for germline specification in C. elegans. Development 126:1–11
Takasaki T, Liu Z, Habara Y et al (2007) MRG-1, an autosome-associated protein, silences X-linked genes and protects germline immortality in Caenorhabditis elegans. Development 134:757–767. doi:10.1242/dev.02771
Tenenhaus C, Subramaniam K, Dunn MA, Seydoux G (2001) PIE-1 is a bifunctional protein that regulates maternal and zygotic gene expression in the embryonic germ line of Caenorhabditis elegans. Genes Dev 15:1031–1040. doi:10.1101/gad.876201
Tenlen JR, Molk JN, London N et al (2008) MEX-5 asymmetry in one-cell C. elegans embryos requires PAR-4- and PAR-1-dependent phosphorylation. Development 135:3665–3675. doi:10.1242/dev.027060
Unhavaithaya Y, Shin TH, Miliaras N et al (2002) MEP-1 and a homolog of the NURD complex component Mi-2 act together to maintain germline-soma distinctions in C. elegans. Cell 111:991–1002
Updike D, Strome S (2010) P granule assembly and function in Caenorhabditis elegans germ cells. J Androl 31:53–60. doi:10.2164/jandrol.109.008292
Updike DL, Hachey SJ, Kreher J, Strome S (2011) P granules extend the nuclear pore complex environment in the C. elegans germ line. J Cell Biol 192:939–948. doi:10.1083/jcb.201010104
Venkatarama T, Lai F, Luo X et al (2010) Repression of zygotic gene expression in the Xenopus germline. Development 137:651–660. doi:10.1242/dev.038554
Wang D, Kennedy S, Conte D et al (2005) Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants. Nature 436:593–597. doi:10.1038/nature04010
Wolf N, Priess J, Hirsh D (1983) Segregation of germline granules in early embryos of Caenorhabditis elegans: an electron microscopic analysis. J Embryol Exp Morphol 73:297–306
Xu L, Fong Y, Strome S (2001) The Caenorhabditis elegans maternal-effect sterile proteins, MES-2, MES-3, and MES-6, are associated in a complex in embryos. Proc Natl Acad Sci USA 98:5061
Zhang Y, Yan L, Zhou Z et al (2009) SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans. Cell 136:308–321. doi:10.1016/j.cell.2008.12.022
Acknowledgments
We thank members of the Seydoux lab for helpful discussions. We gratefully acknowledge funding from NIH (T32 HD007276 to J.W. and HD037047 to G.S.) and the Howard Hughes Medical Institute.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Wang, J.T., Seydoux, G. (2013). Germ Cell Specification. In: Schedl, T. (eds) Germ Cell Development in C. elegans. Advances in Experimental Medicine and Biology, vol 757. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4015-4_2
Download citation
DOI: https://doi.org/10.1007/978-1-4614-4015-4_2
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-4014-7
Online ISBN: 978-1-4614-4015-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)