Skip to main content

Advertisement

SpringerLink
Log in

The functional architecture of the nucleus as analysed by ultrastructural cytochemistry

  • Robert Feulgen Lecture
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Ultrastructural cytochemistry has been, for many years now, a major tool for investigating structure–function relationships in the cell nucleus. It has been essential in approaching the roles which different nuclear structural constituents can play in nuclear functions. This article briefly summarises transmission electron microscopic studies aimed at characterising in situ nuclear architectural domains and their involvement in main nuclear functions, such as DNA replication, hnRNA transcription and pre-mRNA processing. It discusses the importance of ultrastructural cytochemistry in high resolution analyses of intranuclear distribution of chromatin domains and their topological relationships with other structural interphase nuclear constituents. It puts forward the central role of the perichromatin region as a functional nuclear domain. Finally, it attempts to critically evaluate some future applications of ultrastructural investigations of the nucleus and stresses the importance of combining them with light microscopic analyses of living cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Bernhard W (1969) A new staining procedure for electron microscopical cytology. J Ultrastruct Res 27:250–265

    CAS  PubMed  Google Scholar 

  • Beyer AL, Osheim YN (1988) Splice site selection rate of splicing and alternative splicing on nascent transcripts. Genes Dev 2:754–765

    CAS  PubMed  Google Scholar 

  • Biggiogera M, Fakan S (1998) Fine structural specific visualization of RNA on ultrathin sections. J Histochem Cytochem 46:389–395

    CAS  PubMed  Google Scholar 

  • Biggiogera M, Courtens JL, Derenzini M, Fakan S, Hernandez-Verdun D, Risueno MC, Soyer-Gobillard MO (1996) Osmium ammine: review of current applications to visualize DNA in electron microscopy. Biol Cell 87:121–132

    Article  CAS  PubMed  Google Scholar 

  • Biggiogera M, Malatesta M, Abolhassani-Dadras S, Amalric F, Rothblum LI, Fakan S (2001) Revealing the unseen: the organizer region of the nucleolus. J Cell Sci 114:3199–3205

    CAS  PubMed  Google Scholar 

  • Clevenger C, Epstein A (1984) Component of interchromatin granules using a monoclonal antibody and immunogold electron microscopy. Exp Cell Res 151:194–207

    CAS  PubMed  Google Scholar 

  • Cmarko D, Verschure PJ, Martin TE, Dahmus ME, Krause S, Fu XD, van Driel R, Fakan S (1999) Ultrastructural analysis of transcription and splicing in the cell nucleus after bromo-UTP microinjection. Mol Biol Cell 10:211–223

    CAS  PubMed  Google Scholar 

  • Cmarko D, Verschure PJ, Rothblum LI, Hernandez-Verdun D, Amalric F, vanDriel R, Fakan S (2000) Ultrastructural analysis of nucleolar transcription in cells microinjected with 5-bromo-UTP. Histochem Cell Biol 113:131–187

    Article  Google Scholar 

  • Cmarko D, Boe SO, Scassellati C, Szilvay AM, Davanger S, Fu XD, Haukenes G, Kalland KH, Fakan S (2002) Rev inhibition strongly affects intracellular distribution of human immunodeficiency virus type 1 RNAs. J Virol 76:10473–10484

    Article  CAS  PubMed  Google Scholar 

  • Cmarko D, Verschure PJ, Otte AP, van Driel R, Fakan S (2003) Polycomb group gene silencing proteins are concentrated in the perichromatin compartment of the mammalian nucleus. J Cell Sci 116:335–343

    Article  CAS  PubMed  Google Scholar 

  • Cogliati R, Gautier A (1973) Mise en évidence de l’ADN et des polysaccharides à l’aide d’un nouveau réactif “de type Schiff”. C R Acad Sci Paris Ser D 276:3041–3044

    CAS  Google Scholar 

  • Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Gen 2:292–301

    Article  CAS  Google Scholar 

  • Daneholt B (2001) Assembly and transport of a premessenger RNP particle. Proc Natl Acad Sci U S A 98:7012–7017

    Article  CAS  PubMed  Google Scholar 

  • Dreyfuss G, Kim VN, Kataoka N (2002) Messenger-RNA-binding proteins and the messages they carry. Mol Cell Biol 3:195–205

    Article  CAS  Google Scholar 

  • Dundr M, Hebert MD, Karpova TS, Stanek D, Xu H, Shpargel KB, Meier UT, Neugebauer KM, Matera AG, Misteli T (2004) In vivo kinetics of Cajal body components. J Cell Biol 164:831–842

    Article  CAS  PubMed  Google Scholar 

  • Esquivel C, Vázquez-Nin GH, Echeverría O (1989) Evidence of repetitive patterns of chromatin distribution in cell nuclei of rat liver. Acta Anat 136:94–98

    CAS  Google Scholar 

  • Fakan S (1978) High resolution autoradiography studies on chromatin functions. In: Busch H (ed) The cell nucleus, vol 5. Academic, New York, pp 3–54

  • Fakan S (1994) Perichromatin fibrils are in situ forms of nascent transcripts. Trends Cell Biol 4:86–90

    Article  CAS  PubMed  Google Scholar 

  • Fakan S, Bernhard W (1971) Localization of rapidly and slowly labeled nuclear RNA as visualized by high resolution autoradiography. Exp Cell Res 67:129–141

    CAS  PubMed  Google Scholar 

  • Fakan S, Hancock R (1974) Localization of newly-synthesized DNA in a mammalian cell as visualized by high resolution autoradiography. Exp Cell Res 83:95–102

    CAS  PubMed  Google Scholar 

  • Fakan S, Puvion E (1980) The ultrastructural visualization of nucleolar and extranucleolar RNA synthesis and distribution. Int Rev Cytol 65:255–299

    CAS  PubMed  Google Scholar 

  • Fakan S, Puvion E, Spohr G (1976) Localization and characterization of newly synthesized nuclear RNA in isolated rat hepatocytes. Exp Cell Res 99:155–164

    CAS  PubMed  Google Scholar 

  • Fakan S, Leser G, Martin TE (1984) Ultrastructural distribution of nuclear ribonucleoproteins as visualized by immunocytochemistry on thin sections. J Cell Biol 98:358–363

    Article  CAS  PubMed  Google Scholar 

  • Fakan S, Leser G, Martin TE (1986) Immunoelectron microscope visualization of nuclear ribonucleoprotein antigens within spread transcription complexes. J Cell Biol 103:1153–1157

    Article  CAS  PubMed  Google Scholar 

  • Fay FS, Taneja KL, Shenoy S, Lifshitz L, Singer RH (1997) Quantitative digital analysis of diffuse and concentrated nuclear distribution of nascent transcripts, SC35 and poly(A). Exp Cell Res 231:27–37

    Article  CAS  PubMed  Google Scholar 

  • Fomproix N, Percipalle P (2004) An actin-myosin complex on actively transcribing genes. Exp Cell Res 294:140–148

    Article  CAS  PubMed  Google Scholar 

  • Gall JG (2003) The centennial of the Cajal body. Nat Rev Mol Cell Biol 4:975–980

    Article  CAS  PubMed  Google Scholar 

  • Goessens G (1984) Nucleolar structure. Int Rev Cytol 87:107–157

    CAS  PubMed  Google Scholar 

  • Granboulan N, Granboulan P (1965) Cytochimie ultrastructurale du nucléole. II. Etude des sites de synthèse du RNA dans le nucléole et le noyau. Exp Cell Res 38:604–619

    CAS  PubMed  Google Scholar 

  • Guillot PV, Xie SQ, Hollinshead M, Pombo A (2004) Fixation-induced redistribution of hyperphosphorylated RNA polymerase II in the nucleus of human cells. Exp Cell Res 295:460–468

    Article  CAS  PubMed  Google Scholar 

  • Hancock R (2000) A new look at the nuclear matrix. Chromosoma 109:219–225

    Article  CAS  PubMed  Google Scholar 

  • Hancock R (2004) A role for macromolecular crowding effects in the assembly and function of compartments in the nucleus. J Struct Biol 146:281–290

    Article  CAS  PubMed  Google Scholar 

  • Hozak P (1995) Catching RNA polymerase I in flagranti: ribosomal genes are transcribed in the dense fibrillar component of the nucleolus. Exp Cell Res 216:285–289

    Article  CAS  PubMed  Google Scholar 

  • Hozak P, Sasseville AM, Raymond Y, Cook PR (1995) Lamin proteins form an internal nucleoskeleton as well as a peripheral lamina in human cells. J Cell Sci 108:635–344

    CAS  PubMed  Google Scholar 

  • Huang S, Deerinck TJ, Ellisman MH, Spector DL (1994) In vivo analysis of the stability and transport of nuclear poly(A)+ RNA. J Cell Biol 126:877–899

    Article  CAS  PubMed  Google Scholar 

  • Huberman JA, Riggs AD (1968) On the mechanism of DNA replication in mammalian chromosomes. J Mol Biol 32:327–341

    CAS  PubMed  Google Scholar 

  • Jackson DA, Hassan AB, Errington RJ, Cook PR (1993) Visualization of focal sites of transcription within human nuclei. EMBO J 12:1059–1065

    CAS  PubMed  Google Scholar 

  • Janicki SM, Tsukamoto T, Salghetti SE, Tansey WP, Sachidanandam R, Prasanth KV, Ried T, Shav-Tal Y, Bertrand E, Singer RH, Spector DL (2004) From silencing to gene expression: real-time analysis in single cells. Cell 116:683–698

    Article  CAS  PubMed  Google Scholar 

  • Jaunin F, Fakan S (2002) DNA replication and nuclear architecture. J Cell Biochem 85:1–9

    Article  CAS  PubMed  Google Scholar 

  • Jaunin F, Visser AE, Cmarko D, Aten JA, Fakan S (1998) A new immunocytochemical technique for ultrastructural analysis of DNA replication in proliferating cells after application of two halogenated deoxyuridines. J Histochem Cytochem 46:1203–1209

    CAS  PubMed  Google Scholar 

  • Jaunin F, Visser AE, Cmarko D, Aten JA, Fakan S (2000) Fine structural in situ analysis of nascent DNA movement following DNA replication. Exp Cell Res 260:313–323

    Article  CAS  PubMed  Google Scholar 

  • Jones RE, Okamura C, Martin TE (1980) Immunofluorescent localization of the proteins of nuclear ribonucleoprotein complexes. J Cell Biol 86:235–243

    Article  CAS  PubMed  Google Scholar 

  • Kramer J, Zachar Z, Bingham PM (1994) Nuclear pre-mRNA metabolism: channels and tracks. Trends Cell Biol 4:35–37

    Article  CAS  PubMed  Google Scholar 

  • Lamond AI, Spector DL (2003) Nuclear speckles: a model for nuclear organelles. Mol Cell Biol 4:605–612

    Article  CAS  Google Scholar 

  • Leblond CP, el-Alfy M (1996) The eleven stages of the cell cycle, with emphasis on the changes in chromosomes and nucleoli during interphase and mitosis. Anat Rec 252:426–443

    Article  Google Scholar 

  • Leser GP, Escara-Wilke J, Martin TE (1984) Monoclonal antibodies to heterogenous nuclear RNA-protein complexes. The core proteins comprise a conserved group of related polypeptides. J Biol Chem 259:1827–1833

    CAS  PubMed  Google Scholar 

  • Liu Q, Dreyfuss G (1996) A novel nuclear structure containing the survival of motor neurons protein. EMBO J 15:3555–3565

    CAS  PubMed  Google Scholar 

  • Liu DF, el-Alfy M, Leblond CP (1995) DNA changes involved in the formation of metaphase chromosomes, as observed in mouse duodenal crypt cells stained by osmium-amine. II. Tracing nascent DNA by bromodeoxyuridine into structures arising during the S-phase. Anat Rec 242:449–461

    CAS  PubMed  Google Scholar 

  • López-Velázquez G, Márquez J, Ubaldo E, Corkidi G, Echeverría O, Vázquez Nin GH (1996) Three-dimensional analysis of the arrangement of compact chromatin in the nucleus of G0 rat lymphocytes. Histochem Cell Biol 105:153–161

    PubMed  Google Scholar 

  • Malatesta M, Zancanaro C, Martin TE, Chan EKL, Amalric F, Lührmann R, Vogel P, Fakan S (1994a) Cytochemical and immunocytochemical characterization of nuclear bodies during hibernation. Eur J Cell Biol 65:82–93

    CAS  PubMed  Google Scholar 

  • Malatesta M, Zancanaro C, Martin TE, Chan EKL, Amalric F, Lührmann R, Vogel P, Fakan S (1994b) Is the coiled body involved in nucleolar functions? Exp Cell Res 211:415–419

    Article  CAS  PubMed  Google Scholar 

  • Malatesta M, Scassellati C, Meister G, Plöttner O, Bühler D, Sowa G, Martin TE, Keidel E, Fischer U, Fakan S (2004) Ultrastructural characterisation of a nuclear domain highly enriched in survival of motor neuron (SMN) protein. Exp Cell Res 292:312–321

    Article  CAS  PubMed  Google Scholar 

  • Martin TE, Okamura CS (1981) Immunocytochemistry of nuclear hnRNP complexes. In: Busch H (ed) The cell nucleus, vol 9. Academic, New York, pp 119–144

  • Mattick JS (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. Bioessays 25:930–939

    Article  CAS  PubMed  Google Scholar 

  • Misteli T (2001) The concept of self-organization in cellular architecture. J Cell Biol 155:181–185

    Article  CAS  PubMed  Google Scholar 

  • Misteli T, Caceres JF, Spector DL (1997) The dynamics of a pre-mRNA splicing factor in living cells. Nature 387:523–527

    Article  CAS  PubMed  Google Scholar 

  • Molenaar C, Abdulle A, Gena A, Tanke HJ, Dirks RW (2004) Poly(A)+ RNAs roam the cell nucleus and pass through speckle domains in transcriptionally active and inactive cells. J Cell Biol 165:191–202

    Article  CAS  PubMed  Google Scholar 

  • Monneron A, Bernhard W (1969) Fine structural organization of the interphase nucleus in some mammalian cells. J Ultrastruct Res 27:266–288

    CAS  PubMed  Google Scholar 

  • Nash RE, Puvion E, Bernhard W (1975) Perichromatin fibrils as components of rapidly labeled extranucleolar RNA. J Ultrastruct Res 53:395–405

    CAS  PubMed  Google Scholar 

  • O’Keefe RT, Henderson SC, Spector DL (1992) Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific α-satellite DNA sequences. J Cell Biol 116:1095–1110

    Article  PubMed  Google Scholar 

  • Pederson T (2000) Half a century of “the nuclear matrix”. Mol Biol Cell 11:799–805

    CAS  PubMed  Google Scholar 

  • Pestic-Dragovich L, Stojiljkovic L, Philimonenko AA, Nowak G, Ke Y, Settlage RE, Shabanowitz J, Hunt DF, Hozak P, de Lanerolle P (2000) A myosin I isoform in the nucleus. Science 290:337–341

    Article  CAS  PubMed  Google Scholar 

  • Platani M, Goldberg I, Swedlow JR, Lamond AI (2000) In vivo analysis of Cajal body movement, separation, and joining in live human cells. J Cell Biol 151:1561–1574

    Article  CAS  PubMed  Google Scholar 

  • Politz JC, Pederson T (2000) Review: movement of mRNA from transcription site to nuclear pores. J Struct Biol 129:252–257

    Article  CAS  PubMed  Google Scholar 

  • Politz JC, Turft RA, Pederson T, Singer RH (1999) Movement of nuclear poly(A) RNA throughout the interchromatin space in living cells. Cur Biol 9:285–291

    Article  CAS  Google Scholar 

  • Puvion E, Moyne G (1978) Intranuclear migration of newly synthesized extranucleolar ribonucleoproteins. A high resolution quantitative autoradiographical and cytochemical study. Exp Cell Res 115:79–88

    CAS  PubMed  Google Scholar 

  • Puvion E, Puvion-Dutilleul F (1996) Ultrastructure of the nucleus in relation to transcription and splicing: roles of perichromatin fibrils and interchromatin granules. Exp Cell Res 229:217–225

    Article  CAS  PubMed  Google Scholar 

  • Puvion E, Viron A, Assens C, Leduc EH, Jeanteur P (1984) Immunocytochemical identification of nuclear structures containing snRNPs in isolated rat liver cells. J Ultrastruct Res 87:180–189

    CAS  PubMed  Google Scholar 

  • Raska I (2003) Oldies but goldies: searching for Christmas trees within the nucleolar architecture. Trends Cell Biol 13:517–525

    Article  CAS  PubMed  Google Scholar 

  • Raska I, Andrade LE, Ochs RL, Chan EK, Chang CM, Roos G, Tan EM (1991) Immunological and ultrastructural studies of the nuclear coiled body with autoimmune antibodies. Exp Cell Res 195:27–37

    CAS  PubMed  Google Scholar 

  • Roix J, Misteli T (2002) Genomes, proteomes, and dynamic networks in the cell nucleus. Histochem Cell Biol 118:105–116

    CAS  PubMed  Google Scholar 

  • Sacco-Bubulya P, Spector DL (2002) Disassembly of interchromatin granule clusters alters the coordination of transcription and pre-mRNA splicing. J Cell Biol 156:425–436

    Article  CAS  PubMed  Google Scholar 

  • Shumaker DK, Kuczmarski ER, Goldman RD (2003) The nucleoskeleton: lamins and actin are major players in essential nuclear functions. Curr Opin Cell Biol 15:358–366

    Article  CAS  PubMed  Google Scholar 

  • Singh OP, Björkroth B, Masich S, Wieslander L, Daneholt B (1999) The intranuclear movement of Balbiani ring premessenger ribonucleoprotein particles. Exp Cell Res 251:135–146

    Article  CAS  PubMed  Google Scholar 

  • Smetana K, Steele WJ, Busch H (1963) A nuclear ribonucleoprotein network. Exp Cell Res 182:521–533

    Google Scholar 

  • Sobczak-Thepot J, Harper F, Florentin Y, Zindy F, Brechot C, Puvion E (1993) Localization of cyclin A at the sites of cellular DNA replication. Exp Cell Res 206:43–48

    Article  CAS  PubMed  Google Scholar 

  • Solovei I, Cavallo A, Schermelleh L, Jaunin F, Scassellati C, Cmarko D, Cremer C, Fakan S, Cremer T (2002) Spatial preservation of nuclear chromatin architecture during three-dimensional fluorescence in situ hybridization (3D-FISH). Exp Cell Res 276:10–23

    Article  CAS  PubMed  Google Scholar 

  • Spector DL (2003) The dynamics of chromosome organization and gene regulation. Annu Rev Biochem 72:573–608

    Google Scholar 

  • Spector DL, Schrier WH, Busch H (1983) Immunoelectron microscopic localization of snRNPs. Biol Cell 49:1–10

    CAS  PubMed  Google Scholar 

  • Spector DL, Fu XD, Maniatis T (1991) Associations between distinct pre-mRNA splicing components and the cell nucleus. EMBO J 10:3467–3481

    CAS  PubMed  Google Scholar 

  • Stelzer EHK (1995) The intermediate optical system of laser-scanning confocal microscopes. In: Pawley JB (ed) Handbook of biological confocal microscopy. Plenum, New York, pp 139–154

  • Swift H (1962) Nucleoprotein localization in electron micrographs: metal binding and radioautography. In: Harris RJC (ed) The interpretation of ultra-structure. Symposia of the International Society for Cell Biology, vol 1. Academic, New York, pp 213–232

  • Trentani A, Testillano PS, Risueño MC, Biggiogera M (2003) Visualization of transcription sites at the electron microscope. Eur J Histochem 47:195–200

    CAS  PubMed  Google Scholar 

  • van der Ploeg J (2000) Cytochemical nucleic acid research during the twentieth century. Eur J Hictochem 44:7–42

    Google Scholar 

  • van Driel R, Fransz PF, Verschure PJ (2003) The eukaryotic genome: a system regulated at different hierarchical levels. J Cell Sci 116:4067–4075

    Article  PubMed  Google Scholar 

  • Vazquez-Nin GH, Bernhard W (1971) Comparative ultrastructural study of perichromatin- and Balbiani ring granules. J Ultrastruct Res 36:842–860

    CAS  PubMed  Google Scholar 

  • Vazquez-Nin GH, Echeverria OM, Fakan S, Leser G, Martin TE (1990) Immunoelectron microscope localization of snRNPs in the polytene nucleus of salivary glands of Chironomus thummi. Chromosoma 99:44–51

    Google Scholar 

  • Vazquez-Nin GH, Abolhassani-Dadras S, Echeverria OM, Boutinard Rouelle-Rossier V, Fakan S (1996) Phosphorus distribution in perichromatin granules and surrounding nucleoplasm as visualized by electron spectroscopic imaging. Biol Cell 87:171–177

    Article  CAS  PubMed  Google Scholar 

  • Vazquez-Nin GH, Abolhassani-Dadras S, Echeverria OM, Boutinard Rouelle-Rossier V, von Schack ML, Fakan S (1997a) Electron spectroscopic imaging analyses of the distribution of phosphorus in Balbiani ring granules and in the surrounding nucleoplasm. Chromosoma 105:360–368

    Article  CAS  PubMed  Google Scholar 

  • Vazquez-Nin GH, Echeverria OM, Ortiz R, Ubaldo E, Fakan S (1997b) Effects of hypophyseal hormones on transcription and RNA export to the cytoplasm. Exp Cell Res 236:519–526

    Article  CAS  PubMed  Google Scholar 

  • Verschure PJ, van der Kraan I, Manders EMM, Hoogstraten D, Houtsmuller AB, van Driel R (2003) Condensed chromatin domains in the mammalian nucleus are accessible to large macromolecules. EMBO Rep 4:861–866

    Article  CAS  PubMed  Google Scholar 

  • Visa N, Puvion-Dutilleul F, Harper F, Bachellerie JP, Puvion E (1993a) Intranuclear distribution of poly(A) RNA determined by electron microscope in situ hybridization. Exp Cell Res 208:19–34

    Article  CAS  PubMed  Google Scholar 

  • Visa N, Puvion-Dutilleul F, Bachellerie JP, Puvion E (1993b) Intranuclear distribution of U1 and U2 snRNAs visualized by high resolution in situ hybridization: revelation of a novel compartment containing U1 but not U2 snRNA in HeLa cells. Eur J Cell Biol 60:308–321

    CAS  PubMed  Google Scholar 

  • Visser AE, Jaunin F, Fakan S, Aten JA (2000) High resolution analysis of interphase chromosome domains. J Cell Sci 113:2585–2593

    CAS  PubMed  Google Scholar 

  • von Schack ML, Fakan S (1993) The study of the cell nucleus using cryofixation and cryosubstitution. Micron 24:507–519

    Article  Google Scholar 

  • Wansink DG, Schul W, van der Kraan I, van Steensel B, van Driel R, de Jong L (1993) Fluorescent labeling of nascent RNA reveals transcription by RNA polymerase II in domains scattered throughout the nucleus. J Cell Biol 122:282–293

    Article  Google Scholar 

  • Wieslander L, Baurén G, Bernholm K, Jiang WQ, Wetterberg I (1996) Processing of pre-mRNA in polytene nuclei of Chironomus tentans salivary gland cells. Exp Cell Res 229:240–246

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author would like to thank Drs. M. Biggiogera, M. Malatesta and T. Martin for critical reading of the manuscript and constructive comments, Mrs. L. Hautle for the preparation of the manuscript and Mr. W. Blanchard for photographic work. Research in the author’s laboratory has been supported by the Swiss National Science Foundation.

Author information

Authors and Affiliations

  1. Centre of Electron Microscopy, University of Lausanne, Rue du Bugnon 27, 1005, Lausanne, Switzerland

    Stanislav Fakan

Authors
  1. Stanislav Fakan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stanislav Fakan.

Additional information

Robert Feulgen Lecture 2004 presented at the 46th Symposium of the Society for Histochemistry in Prague, Czech Republic, on 22 September 2004

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fakan, S. The functional architecture of the nucleus as analysed by ultrastructural cytochemistry. Histochem Cell Biol 122, 83–93 (2004). https://doi.org/10.1007/s00418-004-0681-1

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-004-0681-1

Keywords

Search

Navigation