Journal of Molecular Evolution

, Volume 66, Issue 1, pp 1–10 | Cite as

The Lengthening of a Giant Protein: When, How, and Why?

  • Olivier Meiniel
  • Robert Meiniel
  • Fabrice Lalloué
  • Robert Didier
  • Marie-Odile Jauberteau
  • Annie Meiniel
  • Daniel Petit


Subcommissural organ (SCO)-spondin is a giant glycoprotein of more than 5000 amino acids found in Vertebrata, expressed in the central nervous system and constitutive of Reissner’s fiber. For the first time, in situ hybridization performed on zebrafish (Danio rerio) embryos shows that the gene encoding this protein is expressed transitionally in the floor plate, the ventral midline of the neural tube, and later in the diencephalic third ventricle roof, the SCO. The modular organization of the protein in Echinodermata (Strongylocentrotus purpuratus), Urochordata (Ciona savignyi and C. intestinalis), and Vertebrata (Teleostei, Amphibia, Aves and Mammalia) is also described. As the thrombospondin type 1 repeat motifs represent an increasingly large part of the protein during Deuterostomia evolution, the duplication mechanisms leading to this complex organization are examined. The functional significance of the particularly well-preserved arrangement of the series of SCO-spondin repeat motifs and thombospondin type 1 repeats is discussed.


SCO-spondin Central nervous system Thrombospondin type 1 repeat SCO-spondin repeat Deuterostomia 



We thank Sridhar Ramachandran of the ZFIN for editing the scospondin gene. We acknowledge the contributions of genome sequencing projects that have generated some sequences useful for our analyses. Special thanks go to Olivier Jaillon at the Genoscope for providing T. nigroviridis sequencing accession numbers and to Kerstin Howe and Mario Caccamo at Sanger for helping with D. rerio genomic data. We are grateful to Bernard and Christine Thisse for their generous collaboration in establishing zebrafish expression patterns. We thank Richard Ryan for proofreading. Work at the UMR 384 is supported by INSERM. O. Meiniel is supported by a DRRT postdoctoral fellowship (FNADT, Région Auvergne-Limousin).

Supplementary material

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  1. Adams JC, Tucker RP (2000) The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins with related roles in neuronal development. Dev Dyn 218:280–299PubMedCrossRefGoogle Scholar
  2. Adams JC (2001) Thrombospondins: multifunctional regulators of cell interaction. Annu Rev Cell Dev Biol 17:25–51PubMedCrossRefGoogle Scholar
  3. Burstyn-Cohen T, Frumkin A, Xu YT, Scherer SS, Klar A (1998) Accumulation of F-spondin in injured peripheral nerve promotes the outgrowth of sensory axons. J Neurosci 18(21):8875–8885PubMedGoogle Scholar
  4. Burstyn-Cohen T, Tzarfaty V, Frumkin A, Feinstein Y, Stoeckli E, Klar A (1999) F-Spondin is required for accurate pathfinding of commissural axons at the floor plate. Neuron 23:233–246PubMedCrossRefGoogle Scholar
  5. Charron F, Tessier-Lavigne M (2005) Novel brain wiring functions for classical morphogens: a role as graded positional cues in axon guidance. Development 132(10):2251–2262PubMedCrossRefGoogle Scholar
  6. Chen H, Herndon ME, Lawler J (2000) The cell biology of thrombospondin 1. Matrix Biol 19:597–614PubMedCrossRefGoogle Scholar
  7. DeFreitas MF, Yoshida CK, Frazier WA, Mendrick DL, Kypta RM, Reichardt LF (1995) Identification of integrin α3β1 as a neuronal thrombospondin receptor mediating neurite outgrowth. Neuron 15:333–343PubMedCrossRefGoogle Scholar
  8. Didier R, Meiniel O, Meiniel A (2007) Molecular cloning and early expression of chick embryo SCO-spondin. Cell Tissue Res 327:111–119PubMedCrossRefGoogle Scholar
  9. Ermisch A (1973) Zur Charakterisierung des Komplexes Subcommissuralorgan-Reissnerscher Faden und seiner Beziehung zum Liquor unter besonderer Berücksichtigung autoradiographisher Untersuchungen sowie funktioneller Aspekte. Math Naturwiss R (Wiss Z Karl Marx Univ Leipzig) 22:297–336Google Scholar
  10. Gobron S, Monnerie H, Meiniel R, Creveaux I, Lehmann W, Lamalle D, Dastugue B, Meiniel A (1996) SCO-spondin: a new member of the thrombospondin family secreted by the subcommissural organ is a candidate in the modulation of neuronal aggregation. J Cell Sci 109:1053–1061PubMedGoogle Scholar
  11. Gobron S, Creveaux I, Meiniel R, Didier R, Dastugue B, Meiniel A (1999) SCO-spondin is evolutionnarily conserved in the central nervous system of the chordate phylum. Neuroscience 88:655–664PubMedCrossRefGoogle Scholar
  12. Gobron S, Creveaux I, Meiniel R, Didier R, Herbet A, Bamdad M, El Bitar F, Dastugue B, Meiniel A (2000) Subcommissural organ/Reissner’s fiber complex: characterization of SCO-spondin, a glycoprotein with potent activity on neurite outgrowth. Glia 32:177–191PubMedCrossRefGoogle Scholar
  13. Goncalves-Mendes N, Simon-Chazottes D, Creveaux I, Meiniel A, Guénet J-L, Meiniel R (2003) Mouse SCO-spondin, a gene of the thrombospondin type 1 repeat (TSR) superfamily expressed in the brain. Gene 312:263–270PubMedCrossRefGoogle Scholar
  14. Guindon S, Gascuel O (2003) PHYML: a simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52(5):696–704 (available at Scholar
  15. Holland ND (1984) Epidermal cells. In: Bereiter-Hahn J, Matoltsy AG, Richards KS (eds) Biology of the Integument. 1. Invertebrates. Springer, New York, 756–774Google Scholar
  16. Holmberg K, Olsson R (1984) The origin of Reissner’s fibre in an appendicularian, Oikopleura dioica. Vidensk. Medd Dansk Naturhist Foren 145:43–52Google Scholar
  17. Jeanmougin F, Thompson JD, Gouy M, Higgins DG, Gibson TJ (1998) Multiple sequence alignment with Clustal X. Trends Biochem Sci 23:403–405PubMedCrossRefGoogle Scholar
  18. Klar A, Baldassare M, Jessel TM (1992) F-spondin: a gene expressed at high levels in the floor plate encodes a secreted protein that promotes neural cell adhesion and neurite extension. Cell 69:95–110PubMedCrossRefGoogle Scholar
  19. Kumar S, Tamura K, Nei M (2004) MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5:150–163PubMedCrossRefGoogle Scholar
  20. Lopez-Avalos MD, Cifuentes M, Grondona JM, Miranda E, Perez J, Fernandez-Llebrez P (1997) Rostral floor plate (flexural organ) secretes glycoproteins immunologically similar to subcommissural organ glycoproteins in dogfish (Scyliorhinus canicula) embryos. Dev Brain Res 102:69–75CrossRefGoogle Scholar
  21. Meiniel O, Meiniel A (2007) The complex multidomain organization of SCO-spondin protein is highly conserved in mammals. Brain Res Rev 53(2):321–327PubMedCrossRefGoogle Scholar
  22. Monnerie H, Dastugue B, Meiniel A (1998) Effect of synthetic peptides derived from conserved domain on chick cortical and spinal-cord neurons in cell cultures. Cell Tissue Res 293:407–418PubMedCrossRefGoogle Scholar
  23. Naumann W, Müller G, Kloss P (1987) Immunoreactive glycoprotein of the subcommissural organ in the embryonic stages of the vertebrate brain. Math Naturwiss R (Wiss Z Karl Marx Univ Leipzig) 36:17–20Google Scholar
  24. Neugebauer KM, Emmett CJ, Venstrom KA, Reichardt LF (1991) Vitronectin and thrombospondin promote retinal neurite outgrowth: developmental regulation and role of integrins. Neuron 6:345–358PubMedCrossRefGoogle Scholar
  25. Oksche A (1961) Vergleichende Untersuchungen über die sekretorische Aktivität des Subcommissuralorgans und den Gliacharakter seiner Zellen. Z Zellforsch 54:549–612PubMedCrossRefGoogle Scholar
  26. Oksche A (1969) The subcommissural organ. J Neuro-Visc Relat (Suppl) 9:111–139Google Scholar
  27. Olsson R (1961) Subcommissural ependyma and pineal organ development in the human fetuses. Gen Comp Endocr 1:117–123PubMedCrossRefGoogle Scholar
  28. Olsson R (1972) Reissner’s fiber in ascidian tadpode larvae. Acta Zool (Stockh) 53:17–21Google Scholar
  29. Olsson R (1993) Reissner’s fiber mechanisms: some common denominators. In: Oksche A, Rodriguez EM, Fernandez-Llebrez P (eds) The subcommissural organ: an ependymal brain gland. Springer Verlag, Berlin, pp 33–39Google Scholar
  30. Olsson R, Wingstrand KG (1954) Reissner’s fibre and the infundibular organ in Amphioxus. Publ Biol Stat (Univ Bergen Årbok) 14:1–14Google Scholar
  31. O’Shea KS, Liu L-HJ, Dixit VM (1991) Thrombospondin and a 140 Kd fragment promote cell adhesion and neurite outgrowth from embryonic central and peripheral neurons and from PC 12 cells. Neuron 7:231–237PubMedCrossRefGoogle Scholar
  32. Osterhout DJ, Frazier WA, Higgins D (1992) Thrombospondin promotes process outgrowth in neurons from the peripheral and central nervous systems. Dev Biol 150:256–265PubMedCrossRefGoogle Scholar
  33. Peruzzo M, Rodriguez S, Delannoy L, Hein S, Rodriguez EM, Oksche A (1987) Ultrastructural immunocytochemical study of the massa caudalis of the subcommissural-Reissner’s fiber complex in lamprey larvae (Geotrica australis). Evidence for a terminal vascular route of secretory material. Cell Tissue Res 247:367–376CrossRefGoogle Scholar
  34. Petit D, Maftah A, Julien R, Petit JM (2006) En bloc duplications, mutation rates and densities of amino acid changes clarify the evolution of vertebrate α1,3/4 fucosyltransferases. J Mol Evol 63(3):353–364PubMedCrossRefGoogle Scholar
  35. Reissner E (1860) Beiträge zur Kenntnis vom Bau des Rückenmarkes von Petromyzon fluviatilis L. Arch Anat Physiol Wiss Med (Leipzig) 545–588Google Scholar
  36. Rodriguez EM, Oksche A, Hein S, Rodriguez S, Yulis R (1984) Comparative immunocytochemical study of the subcommissural organ. Cell Tissue Res 237:427–441PubMedGoogle Scholar
  37. Rodriguez EM, Oksche A, Hein S, Yulis R (1992) Cell biology of subcommissural organ. Int Rev Cytol 135:39–121PubMedCrossRefGoogle Scholar
  38. Rodriguez EM, Jara P, Richter H, Montecinos H, Flandez B, Wiegand R, Oksche A (1993) Evidence for the release of CSF-soluble secretory material from the subcommissural organ, with particular reference to the situation in the human. In: Oksche A, Rodriguez EM, Fernandez-Llebrez P (eds) The subcommissural organ: an ependymal brain gland. Springer Verlag, Berlin, pp 121–131Google Scholar
  39. Rodriguez EM, Del Brio Leon MA, Riera P, Menendez J, Schoebitz K (1996) The floor plate of the hindbrain is a highly specialized gland. Immunocytochemical and ultrastructural characteristics. Dev Brain Res 97:153–168CrossRefGoogle Scholar
  40. Schoebitz K, Garrido O, Heinrichs M, Speer L, Rodriguez E.M (1986) Ontogenetical development of the chick and duck subcommissural organ and immunocytochemical study. Histochemistry 84:31–40PubMedCrossRefGoogle Scholar
  41. Sterba G, Kiessig C, Naumann W, Petter H, Kleim I (1982) The secretion of the subcommissural organ. A comparative immunocytochemical investigation. Cell Tissue Res 226:427–439PubMedCrossRefGoogle Scholar
  42. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882PubMedCrossRefGoogle Scholar
  43. Viehweg J, Naumann WW, Olsson R (1997) Secretory Radial Glia in the Ectoneural System of the Sea Star Asterias rubens (Echinodermata). Acta Zool (Stockholm) 79(2):119–131CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Olivier Meiniel
    • 1
  • Robert Meiniel
    • 1
  • Fabrice Lalloué
    • 2
  • Robert Didier
    • 1
  • Marie-Odile Jauberteau
    • 2
  • Annie Meiniel
    • 1
  • Daniel Petit
    • 3
  1. 1.Faculté de MédecineINSERM, UMR 384Clermont-Ferrand cedexFrance
  2. 2.Faculty of MedicineEA 3842Limoges cedexFrance
  3. 3.INRA, UMR 1061Université de LimogesLimoges cedexFrance

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