Advertisement

Chromosome Research

, Volume 27, Issue 1–2, pp 129–140 | Cite as

Nucleoli in embryos: a central structural platform for embryonic chromatin remodeling?

  • Helena FulkaEmail author
  • Alena Langerova
Review
  • 385 Downloads

Abstract

Nucleoli are the site of ribosomal RNA production and subunit assembly. In contrast to active nucleoli in somatic cells, where three basic sub-compartments can be observed, mammalian oocytes and early embryos contain atypical nucleoli termed “nucleolus-like bodies” or “nucleolus precursor bodies”, respectively. Unlike their somatic counterparts, these structures are composed of dense homogenous fibrillar material and exhibit no polymerase activity. Irrespective of these unusual properties, they have been shown to be absolutely essential for embryonic development, as their microsurgical removal results in developmental arrest. Historically, nucleolus-like and nucleolus precursor bodies have been perceived as passive storage sites of nucleolar material, which is gradually utilized by embryos to construct fully functional nucleoli once they have activated their genome and have started to produce ribosomes. For decades, researchers have been trying to elucidate the composition of these organelles and provide the evidence for their repository role. However, only recently has it become clear that the function of these atypical nucleoli is altogether different, and rather than being involved in ribosome biogenesis, they participate in parental chromatin remodeling, and strikingly, the artificial introduction of a single NPB component is sufficient to rescue the developmental arrest elicited by the NPB removal. In this review, we will describe and summarize the experiments that led to the change in our understanding of these unique structures.

Keywords

Oocyte embryo nucleolus ribosome chromatin remodeling 

Abbreviations

DAXX

Death domain associated protein

G1

Gap 1 phase

GFP

Green fluorescent protein

LLPS

Liquid-liquid phase separation

mRNA

Messenger RNA

NLB

Nucleolus-like body

NOR

Nucleolar organizer region

NPB

Nucleolus precursor body

NSN

Non-surrounded nucleolus

rDNA

Ribosomal DNA

RNase A

Ribonuclease A

rRNA

Ribosomal RNA

S

Synthesis phase

SN

Surrounded nucleolus

SNP

Single nucleotide polymorphism

Notes

Author contribution

HF and AL conceived and jointly wrote the manuscript.

Funding information

Our research is supported by the Czech Science Foundation grant GACR 17-08605S.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Andersen JS, Lyon CE, Fox AH, Leung AKL, Lam YW, Steen H, Mann M, Lamond AI (2002) Directed proteomic analysis of the human nucleolus. Curr Biol 12:1–11CrossRefGoogle Scholar
  2. Andersen JS, Lam YW, Leung AK et al (2005) Nucleolar proteome dynamics. Nature 433:77–83.  https://doi.org/10.1038/nature03207 CrossRefGoogle Scholar
  3. Antoine N, Lepoint A, Baeckeland E, Goessens G (1988) Ultrastructural cytochemistry of the nucleolus in rat oocytes at the end of the folliculogenesis. Histochemistry 89:221–226CrossRefGoogle Scholar
  4. Banani SF, Lee HO, Hyman AA, Rosen MK (2017) Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol 18:285–298.  https://doi.org/10.1038/nrm.2017.7 CrossRefGoogle Scholar
  5. Bjerregaard B, Maddox-Hyttel P (2004) Regulation of ribosomal RNA gene expression in porcine oocytes. Anim Reprod Sci 82–83:605–616.  https://doi.org/10.1016/j.anireprosci.2004.04.023 CrossRefGoogle Scholar
  6. Bochman ML, Paeschke K, Zakian VA (2012) DNA secondary structures: stability and function of G-quadruplex structures. Nat Rev Genet 13:770–780.  https://doi.org/10.1038/nrg3296 CrossRefGoogle Scholar
  7. Boisvert FM, van Koningsbruggen S, Navascues J, Lamond AI (2007) The multifunctional nucleolus. Nat Rev Mol Cell Biol 8:574–585.  https://doi.org/10.1038/nrm2184 CrossRefGoogle Scholar
  8. Bouniol-Baly C, Hamraoui L, Guibert J, Beaujean N, Szöllösi MS, Debey P (1999) Differential transcriptional activity associated with chromatin configuration in fully grown mouse germinal vesicle oocytes. Biol Reprod 60:580–587CrossRefGoogle Scholar
  9. Brunet S, Verlhac MH (2011) Positioning to get out of meiosis: the asymmetry of division. Hum Reprod Update 17:68–75.  https://doi.org/10.1093/humupd/dmq044 CrossRefGoogle Scholar
  10. Burns KH, Viveiros MM, Ren Y, Wang P, DeMayo F, Frail DE, Eppig JJ, Matzuk MM (2003) Roles of NPM2 in chromatin and nucleolar organization in oocytes and embryos. Science 300:633–636.  https://doi.org/10.1126/science.1081813 CrossRefGoogle Scholar
  11. Caudron-Herger M, Pankert T, Seiler J, Nemeth A, Voit R, Grummt I, Rippe K (2015) Alu element-containing RNAs maintain nucleolar structure and function. EMBO J 34:2758–2774.  https://doi.org/10.15252/embj.201591458 CrossRefGoogle Scholar
  12. Cheung MC, LaCroix R, McKenna BK et al (2013) Intracellular protein and nucleic acid measured in eight cell types using deep-ultraviolet mass mapping. Cytometry A 83:540–551.  https://doi.org/10.1002/cyto.a.22277 CrossRefGoogle Scholar
  13. Chouinard LA (1971) A light- and electron-microscope study of the nucleolus during growth of the oocyte in the prepubertal mouse. J Cell Sci 9:637–663Google Scholar
  14. Chouinard LA (1975) A light- and electron-microscope study of the oocyte nucleus during development of the antral follicle in the prepubertal mouse. J Cell Sci 17:589–615Google Scholar
  15. Ciganda M, Williams N (2011) Eukaryotic 5S rRNA biogenesis. Wiley Interdiscip Rev RNA 2:523–533.  https://doi.org/10.1002/wrna.74 CrossRefGoogle Scholar
  16. Debey P, Szöllösi MS, Szöllösi D, Vautier D, Girousse A, Besombes D (1993) Competent mouse oocytes isolated from antral follicles exhibit different chromatin organization and follow different maturation dynamics. Mol Reprod Dev 36:59–74.  https://doi.org/10.1002/mrd.1080360110 CrossRefGoogle Scholar
  17. Emmott E, Hiscox JA (2009) Nucleolar targeting: the hub of the matter. EMBO Rep 10:231–238.  https://doi.org/10.1038/embor.2009.14 CrossRefGoogle Scholar
  18. Fadloun A, Eid A, Torres-Padilla ME (2013) Mechanisms and dynamics of heterochromatin formation during mammalian development: closed paths and open questions. Curr Top Dev Biol 104:1–45.  https://doi.org/10.1016/B978-0-12-416027-9.00001-2 CrossRefGoogle Scholar
  19. Fair T, Hyttel P, Greve T (1995) Bovine oocyte diameter in relation to maturational competence and transcriptional activity. Mol Reprod Dev 42:437–442.  https://doi.org/10.1002/mrd.1080420410 CrossRefGoogle Scholar
  20. Fair T, Hyttel P, Lonergan P, Boland MP (2001) Immunolocalization of nucleolar proteins during bovine oocyte growth, meiotic maturation, and fertilization. Biol Reprod 64:1516–1525CrossRefGoogle Scholar
  21. Fatyol K, Szalay AA (2001) The p14ARF tumor suppressor protein facilitates nucleolar sequestration of hypoxia-inducible factor-1α (HIF-1α) and inhibits HIF-1-mediated transcription. J Biol Chem 276:28421–28429.  https://doi.org/10.1074/jbc.M102847200
  22. Federici L, Arcovito A, Scaglione GL, Scaloni F, Lo Sterzo C, di Matteo A, Falini B, Giardina B, Brunori M (2010) Nucleophosmin C-terminal leukemia-associated domain interacts with G-rich quadruplex forming DNA. J Biol Chem 285:37138–37149.  https://doi.org/10.1074/jbc.M110.166736
  23. Fléchon JE, Kopecný V (1998) The nature of the “nucleolus precursor body” in early preimplantation embryos: a review of fine-structure cytochemical, immunocytochemical and autoradiographic data related to nucleolar function. Zygote 6:183–191CrossRefGoogle Scholar
  24. Frehlick LJ, Eirín-López JM, Ausió J (2007) New insights into the nucleophosmin/nucleoplasmin family of nuclear chaperones. Bioessays 29:49–59.  https://doi.org/10.1002/bies.20512 CrossRefGoogle Scholar
  25. Fulka H, Langerova A (2014) The maternal nucleolus plays a key role in centromere satellite maintenance during the oocyte to embryo transition. Development 141:1694–1704.  https://doi.org/10.1242/dev.105940 CrossRefGoogle Scholar
  26. Fulka J, Moor RM, Loi P (2003) Enucleolation of porcine oocytes. Theriogenology 59:1879–1885CrossRefGoogle Scholar
  27. Fulka H, Martinkova S, Kyogoku H et al (2012) Production of giant mouse oocyte nucleoli and assessment of their protein content. J Reprod Dev 58:371–376CrossRefGoogle Scholar
  28. Geuskens M, Alexandre H (1984) Ultrastructural and autoradiographic studies of nucleolar development and rDNA transcription in preimplantation mouse embryos. Cell Differ 14:125–134CrossRefGoogle Scholar
  29. Griffin J, Emery BR, Huang I, Peterson CM, Carrell DT (2006) Comparative analysis of follicle morphology and oocyte diameter in four mammalian species (mouse, hamster, pig, and human). J Exp Clin Assist Reprod 3:2.  https://doi.org/10.1186/1743-1050-3-2 CrossRefGoogle Scholar
  30. Henras AK, Plisson-Chastang C, O’Donohue M-F et al (2015) An overview of pre-ribosomal RNA processing in eukaryotes. Wiley Interdiscip Rev RNA 6:225–242.  https://doi.org/10.1002/wrna.1269 CrossRefGoogle Scholar
  31. Hernandez-Verdun D (2011) Assembly and disassembly of the nucleolus during the cell cycle. Nucleus 2:189–194.  https://doi.org/10.4161/nucl.2.3.16246 CrossRefGoogle Scholar
  32. Hernandez-Verdun D, Roussel P, Gébrane-Younès J (2002) Emerging concepts of nucleolar assembly. J Cell Sci 115:2265–2270Google Scholar
  33. Hogan B (ed) (1994) Manipulating the mouse embryo: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, PlainviewGoogle Scholar
  34. Inoue A, Aoki F (2010) Role of the nucleoplasmin 2 C-terminal domain in the formation of nucleolus-like bodies in mouse oocytes. FASEB J 24:485–494.  https://doi.org/10.1096/fj.09-143370 CrossRefGoogle Scholar
  35. Itakura AK, Futia RA, Jarosz DF (2018) It pays to be in phase. Biochemistry 57:2520–2529.  https://doi.org/10.1021/acs.biochem.8b00205 CrossRefGoogle Scholar
  36. Jukam D, Shariati SAM, Skotheim JM (2017) Zygotic genome activation in vertebrates. Dev Cell 42:316–332.  https://doi.org/10.1016/j.devcel.2017.07.026 CrossRefGoogle Scholar
  37. Kobayashi T (2014) Ribosomal RNA gene repeats, their stability and cellular senescence. Proc Jpn Acad Ser B Phys Biol Sci 90:119–129.  https://doi.org/10.2183/pjab.90.119 CrossRefGoogle Scholar
  38. Kopecný V, Landa V, Pavlok A (1995) Localization of nucleic acids in the nucleoli of oocytes and early embryos of mouse and hamster: an autoradiographic study. Mol Reprod Dev 41:449–458.  https://doi.org/10.1002/mrd.1080410407 CrossRefGoogle Scholar
  39. Kopecny V, Biggiogera M, Laurincik J, Pivko J, Grafenau P, Martin TE, Fu XD, Fakan S (1996) Fine structural cytochemical and immunocytochemical analysis of nucleic acids and ribonucleoprotein distribution in nuclei of pig oocytes and early preimplantation embryos. Chromosoma 104:561–574CrossRefGoogle Scholar
  40. Kopecný V, Landa V, Malatesta M et al (1996) Immunoelectron microscope analyses of rat germinal vesicle-stage oocyte nucleolus-like bodies. Reprod Nutr Dev 36:667–679Google Scholar
  41. Kyogoku H, Fulka J, Wakayama T, Miyano T (2014) De novo formation of nucleoli in developing mouse embryos originating from enucleolated zygotes. Development 141:2255–2259.  https://doi.org/10.1242/dev.106948 CrossRefGoogle Scholar
  42. Laskey RA, Honda BM, Mills AD, Finch JT (1978) Nucleosomes are assembled by an acidic protein which binds histones and transfers them to DNA. Nature 275:416–420CrossRefGoogle Scholar
  43. Laurincik J, Bjerregaard B, Strejcek F, Rath D, Niemann H, Rosenkranz C, Ochs RL, Maddox-Hyttel P (2004) Nucleolar ultrastructure and protein allocation in in vitro produced porcine embryos. Mol Reprod Dev 68:327–334.  https://doi.org/10.1002/mrd.20088 CrossRefGoogle Scholar
  44. Lee MT, Bonneau AR, Giraldez AJ (2014) Zygotic genome activation during the maternal-to-zygotic transition. Annu Rev Cell Dev Biol 30:581–613.  https://doi.org/10.1146/annurev-cellbio-100913-013027 CrossRefGoogle Scholar
  45. Levi M, Ghetler Y, Shulman A, Shalgi R (2013) Morphological and molecular markers are correlated with maturation-competence of human oocytes. Hum Reprod 28:2482–2489.  https://doi.org/10.1093/humrep/det261 CrossRefGoogle Scholar
  46. Lewis PW, Elsaesser SJ, Noh KM, Stadler SC, Allis CD (2010) Daxx is an H3.3-specific histone chaperone and cooperates with ATRX in replication-independent chromatin assembly at telomeres. Proc Natl Acad Sci U S A 107:14075–14080.  https://doi.org/10.1073/pnas.1008850107 CrossRefGoogle Scholar
  47. Lin CJ, Koh FM, Wong P, Conti M, Ramalho-Santos M (2014) Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote. Dev Cell 30:268–279.  https://doi.org/10.1016/j.devcel.2014.06.022 CrossRefGoogle Scholar
  48. McStay B (2016) Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination. Genes Dev 30:1598–1610.  https://doi.org/10.1101/gad.283838.116 CrossRefGoogle Scholar
  49. Mekhail K, Gunaratnam L, Bonicalzi M-E, Lee S (2004) HIF activation by pH-dependent nucleolar sequestration of VHL. Nat Cell Biol 6:642–647.  https://doi.org/10.1038/ncb1144 CrossRefGoogle Scholar
  50. Mitrea DM, Cika JA, Guy CS, Ban D, Banerjee PR, Stanley CB, Nourse A, Deniz AA, Kriwacki RW (2016) Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA. Elife 5.  https://doi.org/10.7554/eLife.13571
  51. Mitrea DM, Cika JA, Stanley CB, Nourse A, Onuchic PL, Banerjee PR, Phillips AH, Park CG, Deniz AA, Kriwacki RW (2018) Self-interaction of NPM1 modulates multiple mechanisms of liquid-liquid phase separation. Nat Commun 9:842.  https://doi.org/10.1038/s41467-018-03255-3 CrossRefGoogle Scholar
  52. Monti M, Zanoni M, Calligaro A, Ko MSH, Mauri P, Redi CA (2013) Developmental arrest and mouse antral not-surrounded nucleolus oocytes. Biol Reprod 88(2):2.  https://doi.org/10.1095/biolreprod.112.103887 Google Scholar
  53. Moore GP, Lintern-Moore S, Peters H, Faber M (1974) RNA synthesis in the mouse oocyte. J Cell Biol 60:416–422CrossRefGoogle Scholar
  54. Morovic M, Strejcek F, Nakagawa S, Deshmukh RS, Murin M, Benc M, Fulka H, Kyogoku H, Pendovski L, Fulka J, Laurincik J (2017) Mouse oocytes nucleoli rescue embryonic development of porcine enucleolated oocytes. Zygote 25:675–685.  https://doi.org/10.1017/S0967199417000491 CrossRefGoogle Scholar
  55. Morozov VM, Gavrilova EV, Ogryzko VV, Ishov AM (2012) Dualistic function of Daxx at centromeric and pericentromeric heterochromatin in normal and stress conditions. Nucleus 3:276–285.  https://doi.org/10.4161/nucl.20180 CrossRefGoogle Scholar
  56. Mullineux S-T, Lafontaine DLJ (2012) Mapping the cleavage sites on mammalian pre-rRNAs: where do we stand? Biochimie 94:1521–1532.  https://doi.org/10.1016/j.biochi.2012.02.001 CrossRefGoogle Scholar
  57. Ogushi S, Saitou M (2010) The nucleolus in the mouse oocyte is required for the early step of both female and male pronucleus organization. J Reprod Dev 56:495–501CrossRefGoogle Scholar
  58. Ogushi S, Palmieri C, Fulka H, Saitou M, Miyano T, Fulka J (2008) The maternal nucleolus is essential for early embryonic development in mammals. Science 319:613–616.  https://doi.org/10.1126/science.1151276 CrossRefGoogle Scholar
  59. Ogushi S, Yamagata K, Obuse C, Furuta K, Wakayama T, Matzuk MM, Saitou M (2017) Reconstitution of the oocyte nucleolus in mice through a single nucleolar protein, NPM2. J Cell Sci 130:2416–2429.  https://doi.org/10.1242/jcs.195875 CrossRefGoogle Scholar
  60. Philpott A, Leno GH, Laskey RA (1991) Sperm decondensation in Xenopus egg cytoplasm is mediated by nucleoplasmin. Cell 65:569–578CrossRefGoogle Scholar
  61. Pikó L, Clegg KB (1982) Quantitative changes in total RNA, total poly(A), and ribosomes in early mouse embryos. Dev Biol 89:362–378CrossRefGoogle Scholar
  62. Raška I, Koberna K, Malínský J, Fidlerová H, Mašata M (2004) The nucleolus and transcription of ribosomal genes. Biol Cell 96:579–594.  https://doi.org/10.1016/j.biolcel.2004.04.015 CrossRefGoogle Scholar
  63. Schmidt EV (1999) The role of c-myc in cellular growth control. Oncogene 18:2988–2996.  https://doi.org/10.1038/sj.onc.1202751 CrossRefGoogle Scholar
  64. Scognamiglio PL, Di Natale C, Leone M et al (2014) G-quadruplex DNA recognition by nucleophosmin: new insights from protein dissection. Biochim Biophys Acta 1840:2050–2059.  https://doi.org/10.1016/j.bbagen.2014.02.017 CrossRefGoogle Scholar
  65. Shav-Tal Y, Blechman J, Darzacq X, Montagna C, Dye BT, Patton JG, Singer RH, Zipori D (2005) Dynamic sorting of nuclear components into distinct nucleolar caps during transcriptional inhibition. MBoC 16:2395–2413.  https://doi.org/10.1091/mbc.e04-11-0992 CrossRefGoogle Scholar
  66. Shishova KV, Lavrentyeva EA, Dobrucki JW, Zatsepina OV (2015) Nucleolus-like bodies of fully-grown mouse oocytes contain key nucleolar proteins but are impoverished for rRNA. Dev Biol 397:267–281.  https://doi.org/10.1016/j.ydbio.2014.11.022 CrossRefGoogle Scholar
  67. Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D (2008) Nucleolus: the fascinating nuclear body. Histochem Cell Biol 129:13–31.  https://doi.org/10.1007/s00418-007-0359-6 CrossRefGoogle Scholar
  68. Stark LA, Dunlop MG (2005) Nucleolar sequestration of RelA (p65) regulates NF-kappaB-driven transcription and apoptosis. Mol Cell Biol 25:5985–6004.  https://doi.org/10.1128/MCB.25.14.5985-6004.2005 CrossRefGoogle Scholar
  69. Strunk BS, Karbstein K (2009) Powering through ribosome assembly. RNA 15:2083–2104.  https://doi.org/10.1261/rna.1792109 CrossRefGoogle Scholar
  70. Sutovský P, Jelínková L, Antalíková L, Motlík J (1993) Ultrastructural cytochemistry of the nucleus and nucleolus in growing rabbit oocytes. Biol Cell 77:173–180CrossRefGoogle Scholar
  71. Svoboda P (2017) Mammalian zygotic genome activation. Semin Cell Dev Biol.  https://doi.org/10.1016/j.semcdb.2017.12.006
  72. Tsukamoto S, Kuma A, Murakami M, Kishi C, Yamamoto A, Mizushima N (2008) Autophagy is essential for preimplantation development of mouse embryos. Science 321:117–120.  https://doi.org/10.1126/science.1154822 CrossRefGoogle Scholar
  73. Verlhac M-H, Terret M-E (2016) Oocyte maturation and development. F1000Res 5.  https://doi.org/10.12688/f1000research.7892.1
  74. Verlhac M-H, Terret M-E, Pintard L (2010) Control of the oocyte-to-embryo transition by the ubiquitin-proteolytic system in mouse and C. elegans. Curr Opin Cell Biol 22:758–763.  https://doi.org/10.1016/j.ceb.2010.09.003 CrossRefGoogle Scholar
  75. Voon HPJ, Wong LH (2016) New players in heterochromatin silencing: histone variant H3.3 and the ATRX/DAXX chaperone. Nucleic Acids Res 44:1496–1501.  https://doi.org/10.1093/nar/gkw012 CrossRefGoogle Scholar
  76. Wakayama T, Rodriguez I, Perry AC et al (1999) Mice cloned from embryonic stem cells. Proc Natl Acad Sci U S A 96:14984–14989CrossRefGoogle Scholar
  77. Warner JR (1999) The economics of ribosome biosynthesis in yeast. Trends Biochem Sci 24:437–440CrossRefGoogle Scholar
  78. Wassarman PM, Josefowicz WJ (1978) Oocyte development in the mouse: an ultrastructural comparison of oocytes isolated at various stages of growth and meiotic competence. J Morphol 156:209–235.  https://doi.org/10.1002/jmor.1051560206 CrossRefGoogle Scholar
  79. Zatsepina OV, Bouniol-Baly C, Amirand C, Debey P (2000) Functional and molecular reorganization of the nucleolar apparatus in maturing mouse oocytes. Dev Biol 223:354–370.  https://doi.org/10.1006/dbio.2000.9762 CrossRefGoogle Scholar
  80. Zhou X, Liao W-J, Liao J-M, Liao P, Lu H (2015) Ribosomal proteins: functions beyond the ribosome. J Mol Cell Biol 7:92–104.  https://doi.org/10.1093/jmcb/mjv014 CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Institute of Animal Science, v.v.i.Prague 10Czech Republic
  2. 2.Institute of Molecular Genetics ASCR, v.v.i.Prague 4Czech Republic
  3. 3.Institute of Experimental Medicine ASCR, v.v.i.Prague 4Czech Republic
  4. 4.GENNET s.r.o.Prague 7Czech Republic

Personalised recommendations