Abstract
In 1906, the Spanish neurobiologist Santiago Ramón y Cajal was awarded the Nobel Prize in Physiology or Medicine in recognition of his work on the structure of neurons and their connections. Cajal is commonly regarded as the father of modern neuroscience. What is less well known is that Cajal also had a great interest in intracellular neuronal structures and developed the reduced silver nitrate method for the study of neurofibrils (neurofilaments) and nuclear subcompartments. It was in 1903 that Cajal discovered the “accessory body” (“Cajal body”) and seven years later, published an article on the organization of the cell nucleus in mammalian neurons that represents a masterpiece of nuclear structure at the light microscopy level. In addition to the accessory body, it includes the analysis of several nuclear components currently recognized as fibrillar centers of the nucleolus, nuclear speckles of splicing factors, transcription foci, nuclear matrix, and the double nuclear membrane. The aim of this article is to revisit Cajal’s contributions to the knowledge of the neuronal nucleus in light of our current understanding of nuclear structure and function.
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References
Andrade LE, Chan EK, Raska I, Peebles CL, Roos G, Tan EM (1991) Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin. J Exp Med 173:1407–1419
Athias M (1905) Anatomia da cellula nervosa. Lisboa
Berciano MT, Novell M, Villagra NT, Casafont I, Bengoechea R, Val–Bernal JF, Lafarga M (2007) Cajal body number and nucleolar size correlate with the cell body mass in human sensory ganglia neurons. J Struct Biol 158:410–420
Cajal SR (1898) Histología normal y técnica micrográfica. Libreria Pascual Aguilar, Valencia
Cajal SR (1903) Un sencillo método de coloración selectiva del retículo protoplasmático y sus efectos en diversos órganos nerviosos. Trab Lab Invest Biol 2:129–221
Cajal SR (1909) Histologie du système nerveux de l’homme et des vertébrés. Maloine, Paris
Cajal SR (1910) El núcleo de las células piramidales del cerebro humano y de algunos mamíferos. Trab Lab Invest Biol 8:27–62
Cajal SR (1923) Recuerdos de mi vida: historia de mi labor científica. Imprenta de Juan Pueyo, Madrid
Carmo-Fonseca M (2002) New clues to the function of the Cajal body. EMBO Rep 3:726–727
Carvalho T, Almeida F, Calapez A, Lafarga M, Berciano MT, Carmo-Fonseca M (1999) The spinal muscular atrophy disease gene product, SMN: a link between snRNP biogenesis and the Cajal (coiled) body. J Cell Biol 147:715–728
Casafont I, Navascues J, Pena E, Lafarga M, Berciano MT (2006) Nuclear organization and dynamics of transcription sites in rat sensory ganglia neurons detected by incorporation of 5'-fluorouridine into nascent RNA. Neuroscience 140:453–462
Cioce M, Lamond AI (2005) Cajal bodies: a long history of discovery. Annu Rev Cell Dev Biol 21:105–131
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
DeFelipe J (2002) Sesquicentenary of the birthday of Santiago Ramón y Cajal, the father of modern neuroscience. Trends Neurosci 25:481–484
Dimova RN, Markou DV, Gajdardjieva MD, Dabeva A, Hadjiolov A (1982) Electron microscopic localization of silver staining NOR-proteins in rat liver nucleoli upon d-galactosamine block of transcription. Eur J Cell Biol 28:272–277
Gall JG (2000) Cajal bodies: the first 100 years. Annu Rev Cell Dev Biol 16:273–300
Gall JG (2003) The centennial of the Cajal body. Nat Rev Mol Cell Biol 4:975–980
Gall JG, Bellini M, Wu Z, Murphy C (1999) Assembly of the nuclear transcription and processing machinery: Cajal bodies (coiled bodies) and transcriptosomes. Mol Biol Cell 10:4385–4402
Garcia-Segura LM, Berciano MT, Lafarga M (1993) Nuclear compartmentalization in transcriptionally activated hypothalamic neurons. Biol Cell 77:143–154
Haggar RA (1957) Behavior of the accessory body of Cajal during axon reaction. J Comp Neurol 108:269–283
Hardin JH, Spicer SS, Greene WB (1969) The paranucleolar structure, accessory body of Cajal, sex chromatin, and related structures in nuclei of rat trigeminal neurons: a cytochemical and ultrastructural study. Anat Rec 164:403–431
Hendzel MJ, Kruhlak MJ, Bazett-Jones DP (1998) Organization of highly acetylated chromatin around sites of heterogeneous nuclear RNA accumulation. Mol Biol Cell 9:2491–2507
Hervás JP, Lafarga M (1983) Light and electron microscopic characterization of the “accessory body” of Cajal in the neuronal nucleus. In: Grisolia S, Guerri C, Samson F, Norton S, Reinoso-Suárez F (eds) Ramón y Cajal’s contribution to the neurosciences. Elsevier, Amsterdam
Hervás JP, Santa Cruz MC, Crespo D, Villegas J, Lafarga M (1982) Ultracytochemical approach to the coiled body in neurosecretory cells. Biol Cell 45:15–16
Holmgren E (1900) Studien in der feineren Anatomie der Nervenzellen. Anat Hefte 15:1–90
Kaiser TE, Intine RV, Dundr M (2008) De novo formation of a subnuclear body. Science 322:1713–1717
Lache IG (1906) L’aspect du noyau de la cellula nerveuse dans le méthode a l’argent reduit. Anat Anz 28:161–168
Lafarga M, Hervas JP, Santa-Cruz MC, Villegas J, Crespo D (1983) The “accessory body” of Cajal in the neuronal nucleus. A light and electron microscopic approach. Anat Embryol (Berl) 166:19–30
Lafarga M, Gonzalez C, Berciano MT (1986) An improved cytological silver staining method for the demonstration of neuronal nuclear bodies. J Neurosci Methods 18:317–324
Lafarga M, Andres MA, Fernandez-Viadero C, Villegas J, Berciano MT (1995) Number of nucleoli and coiled bodies and distribution of fibrillar centres in differentiating Purkinje neurons of chick and rat cerebellum. Anat Embryol (Berl) 191:359–367
Lafarga M, Berciano MT, Garcia-Segura LM, Andres MA, Carmo-Fonseca M (1998) Acute osmotic/stress stimuli induce a transient decrease of transcriptional activity in the neurosecretory neurons of supraoptic nuclei. J Neurocytol 27:205–217
Lamond AI, Carmo-Fonseca M (1993) The coiled body. Trends Cell Biol 3:198–204
Lamond AI, Spector DL (2003) Nuclear speckles: a model for nuclear organelles. Nat Rev Mol Cell Biol 4:605–612
Levi G (1896) Su alcune particolarità di struttura del nucleo delle cellule nervose. Riv Patol Nerv Ment 1:141–149
Li B, Carey M, Workman JL (2007) The role of chromatin during transcription. Cell 128:707–719
Marinesco G (1905) Recherches sur le noyau et le nucléole de la cellule nerveuse à l'état normal et pathologique. J Psychol Neurol 5:151–172
Marinesco G (1909) La cellule nerveuse. Doin, Paris
Matera AG (1999) Nuclear bodies: multifaceted subdomains of the interchromatin space. Trends Cell Biol 9:302–308
Matera AG, Shpargel KB (2006) Pumping RNA: nuclear bodybuilding along the RNP pipeline. Curr Opin Cell Biol 18:317–324
Monneron A, Bernhard W (1969) Fine structural organization of the interphase nucleus in some mammalian cells. J Ultrastruct Res 27:266–288
Morris GE (2008) The Cajal body. Biochim Biophys Acta 1783:2108–2115
Nayyar RP, Barr ML (1968) Histochemical studies on the accessory body of Cajal in neurones of the cat. J Comp Neurol 132:125–134
Nickerson J (2001) Experimental observations of a nuclear matrix. J Cell Sci 114:463–474
Pebusque MJ, Seïte R (1981) Electron microscopic studies of silver-stained proteins in nucleolar organizer regions: location in nucleoli of rat sympathetic neurons during light and dark periods. J Cell Sci 51:85–94
Pederson T (2000) Half a century of “the nuclear matrix”. Mol Biol Cell 11:799–805
Pena E, Berciano MT, Fernandez R, Ojeda JL, Lafarga M (2001) Neuronal body size correlates with the number of nucleoli and Cajal bodies, and with the organization of the splicing machinery in rat trigeminal ganglion neurons. J Comp Neurol 430:250–263
Peters A, Palay SL, Webster H (1991) The fine structure of the nervous system. Neurons and their supporting cells, 3rd edn. Oxford University Press, New York
Raska I, Ochs RL, Andrade LEC, Chan EKL, Burlingame R, Peebles C, Gruol D, Tan EM (1990) Association between the nucleolus and the coiled body. J Struct Biol 104:120–127
Raska I, Shaw PJ, Cmarko D (2006) New insights into nucleolar architecture and activity. Int Rev Cytol 255:177–235
Risueño MC, Medina JF (1986) The nucleolar structure in plant cells. Cell Biol Rev 7:1–163
Risueño MC, Fernández-Gómez E, Giménez-Martín G (1973) Nucleoli under the electron microscope by silver impregnation. Mikroskopie 29:292–298
Ruzicka W (1899) Zur Geschichte und Kenntnis der feineren Strcktur der Nucleolen centrallen Nervenzellen. Anat Anz 16:557–563
Santama N, Dotti CG, Lamond AI (1996) Neuronal differentiation in the rat hippocampus involves a stage-specific reorganization of subnuclear structure both in vivo and in vitro. Eur J Neurosci 8:892–905
Shpargel KB, Matera AG (2005) Gemin proteins are required for efficient assembly of Sm-class ribonucleoproteins. Proc Natl Acad Sci U S A 102:17372–17377
Sleeman JE, Ajuh P, Lamond AI (2001) snRNP protein expression enhances the formation of Cajal bodies containing p80-coilin and SMN. J Cell Sci 114:4407–4419
Stanek D, Neugebauer KM (2006) The Cajal body: a meeting place for spliceosomal snRNPs in the nuclear maze. Chromosoma 115:343–354
Takeuchi IK, Takeuchi YK (1984) Interchromatin granules in the dividing embryonic ectoderm cells of postimplantation rat embryos: an electron microscopic silver-staining study. J Electron Microsc (Tokyo) 33:151–159
Tello F (1904) Las neurofibrillas en los vertebrados inferiores. Trab Lab Invest Biol 3:113–151
Thiry M (1995) Behavior of interchromatin granules during the cell cycle. Eur J Cell Biol 68:14–24
Thompson BK, Haggar RA, Barr ML (1957) The accessory body of Cajal in nerve cell nuclei of the cat. J Comp Neurol 108:253–267
Tucker KE, Matera AG (2005) The Cajal body: a nuclear gathering place. In: Hemmerich P, Diekmann S (eds) Vision of the cell nucleus. American Scientific Publishers, Stevenson Ranch
Tucker KE, Berciano MT, Jacobs EY, LePage DF, Shpargel KB, Rossire JJ, Chan EK, Lafarga M, Conlon RA, Matera AG (2001) Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product. J Cell Biol 154:293–307
Wei X, Somanathan S, Samarabandu J, Berezney R (1999) Three-dimensional visualization of transcription sites and their association with splicing factor-rich nuclear speckles. J Cell Biol 146:543–558
Acknowledgements
We thank Dr. José M. López-Cepero for kindly providing the micrograph of Fig. 3b. This work was supported by the following grants: “Dirección General de Investigacion” of Spain (BFU2008-00175) and “Centro de Investigación Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED; CB06/05/0037)” from Spain.
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Lafarga, M., Casafont, I., Bengoechea, R. et al. Cajal’s contribution to the knowledge of the neuronal cell nucleus. Chromosoma 118, 437–443 (2009). https://doi.org/10.1007/s00412-009-0212-x
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DOI: https://doi.org/10.1007/s00412-009-0212-x