Cellular and Molecular Neurobiology

, Volume 32, Issue 2, pp 279–287 | Cite as

Existence of Tenascin-C Isoforms in Rat that Contain the Alternatively Spliced AD1 Domain are Developmentally Regulated During Hippocampal Development

  • J. GarwoodEmail author
  • U. Theocharidis
  • V. Calco
  • A. Dobbertin
  • A. FaissnerEmail author
Original Research


Tenascin-C (TN-C) is a multimodular glycoprotein of the extracellular matrix which is important for the development of the nervous system and has a range of different functions which are mediated by the different protein domains present. TN-C contains eight constitutive fibronectin type III (FNIII) domains and a region of alternatively spliced FNIII domains. In the mouse and chick, six of these domains have been described and characterized, whereas in human there are nine of them. In this report, we show that seven alternatively spliced FNIII domains exist in rat and describe the differential expression pattern of the additional domain AD1 during embryonic and postnatal rat brain development. The AD1 domain of rat is homologous to the ones described in human and chick proteins but does not exist in mouse. Its expression can be located to the developing rat hippocampus and the lining of the lateral ventricle, regions where the TN-C protein may affect the behavior of stem and progenitor cells. During hippocampal development AD1 and the other alternatively spliced domains are differentially expressed as shown by RT-PCRs, immunocytochemistry and in situ hybridizations.


Extracellular matrix Central nervous system Glycoprotein Neurite outgrowth 





Fibronectin type III domain


Reverse transcription-polymerase chain reaction


Extracellular matrix


Central nervous system


Epidermal growth factor


Platelet-derived growth factor


Ventricular zone


Cornu ammonis


Matrix metalloproteinase


Transforming growth factor



The authors thank Tim Czopka for the TN-C riboprobe, Anke Mommsen for excellent technical assistance, and Corinna Zimmermann for her help. This study was supported by the CNRS, German Research Council (DFG SPP, Molecular and Cellular Basis of CNS Repair Fa 159/11-1,2,3), the Association pour la Recherche contre le Cancer (ARC), and the International Spinal Research Trust (ISRT).


  1. Bartsch S, Bartsch U, Dorries U, Faissner A, Weller A, Ekblom P, Schachner M (1992) Expression of tenascin in the developing and adult cerebellar cortex. J Neurosci 12:736–749PubMedGoogle Scholar
  2. Berndt A, Anger K, Richter P, Borsi L, Brack S, Silacci M, Franz M, Wunderlich H, Gajda M, Zardi L et al (2006) Differential expression of tenascin-C splicing domains in urothelial carcinomas of the urinary bladder. J Cancer Res Clin Oncol 132:537–546PubMedCrossRefGoogle Scholar
  3. Chiquet-Ehrismann R, Chiquet M (2003) Tenascins: regulation and putative functions during pathological stress. J Pathol 200:488–499PubMedCrossRefGoogle Scholar
  4. Chiquet-Ehrismann R, Mackie EJ, Pearson CA, Sakakura T (1986) Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell 47:131–139PubMedCrossRefGoogle Scholar
  5. Crossin KL (1996) Tenascin: a multifunctional extracellular matrix protein with a restricted distribution in development and disease. J Cell Biochem 61:592–598PubMedCrossRefGoogle Scholar
  6. Czopka T, von Holst A, Schmidt G, Ffrench-Constant C, Faissner A (2009) Tenascin C and tenascin R similarly prevent the formation of myelin membranes in a RhoA-dependent manner, but antagonistically regulate the expression of myelin basic protein via a separate pathway. Glia 57:1790–1801PubMedCrossRefGoogle Scholar
  7. Czopka T, von Holst A, Ffrench-Constant C, Faissner A (2010) Regulatory mechanisms that mediate tenascin C-dependent inhibition of oligodendrocyte precursor differentiation. J Neurosci 30:12333–122310CrossRefGoogle Scholar
  8. Deller T, Haas CA, Naumann T, Joester A, Faissner A, Frotscher M (1997) Up-regulation of astrocyte-derived tenascin-C correlates with neurite outgrowth in the rat dentate gyrus after unilateral entorhinal cortex lesion. Neuroscience 81:829–846PubMedCrossRefGoogle Scholar
  9. Derr LB, Chiquet-Ehrismann R, Gandour-Edwards R, Spence J, Tucker RP (1997) The expression of tenascin-C with the AD1 variable repeat in embryonic tissues, cell lines and tumors in various vertebrate species. Differentiation 62:71–82PubMedCrossRefGoogle Scholar
  10. Dobbertin A, Czvitkovich S, Theocharidis U, Garwood J, Andrews MR, Properzi F, Lin R, Fawcett JW, Faissner A (2010) Analysis of combinatorial variability reveals selective accumulation of the fibronectin type III domains B and D of tenascin-C in injured brain. Exp Neurol 225:60–73PubMedCrossRefGoogle Scholar
  11. Faissner A (1997) The tenascin gene family in axon growth and guidance. Cell Tissue Res 290:331–341PubMedCrossRefGoogle Scholar
  12. Faissner A, Kruse J (1990) J1/tenascin is a repulsive substrate for central nervous system neurons. Neuron 5:627–637PubMedCrossRefGoogle Scholar
  13. Faissner A, Steindler D (1995) Boundaries and inhibitory molecules in developing neural tissues. Glia 13:233–254PubMedCrossRefGoogle Scholar
  14. Faissner A, Kruse J, Kuhn K, Schachner M (1990) Binding of the J1 adhesion molecules to extracellular matrix constituents. J Neurochem 54:1004–1015PubMedCrossRefGoogle Scholar
  15. Fischer D, Tucker RP, Chiquet-Ehrismann R, Adams JC (1997) Cell-adhesive responses to tenascin-C splice variants involve formation of fascin microspikes. Mol Biol Cell 8:2055–2075PubMedGoogle Scholar
  16. Garcion E, Faissner A, Ffrench-Constant C (2001) Knockout mice reveal a contribution of the extracellular matrix molecule tenascin-C to neural precursor proliferation and migration. Development 128:2485–2496PubMedGoogle Scholar
  17. Garcion E, Halilagic A, Faissner A, Ffrench-Constant C (2004) Generation of an environmental niche for neural stem cell development by the extracellular matrix molecule tenascin C. Development 131:3423–3432PubMedCrossRefGoogle Scholar
  18. Garwood J, Heck N, Rigato F, Faissner A (eds) (2001a) The extracellular matrix in neural development, plasticity, and regeneration. Humana Press Inc., TotowaGoogle Scholar
  19. Garwood J, Rigato F, Heck N, Faissner A (2001b) Tenascin glycoproteins and the complementary ligand DSD-1-PG/phosphacan-structuring the neural extracellular matrix during development and repair. Restor Neurol Neurosci 19:51–64PubMedGoogle Scholar
  20. Garwood J, Garcion E, Dobbertin A, Heck N, Calco V, Ffrench-Constant C, Faissner A (2004) The extracellular matrix glycoprotein tenascin-C is expressed by oligodendrocyte precursor cells and required for the regulation of maturation rate, survival and responsiveness to platelet-derived growth factor. Eur J Neurosci 20:2524–2540PubMedCrossRefGoogle Scholar
  21. Gates MA, Thomas LB, Howard EM, Laywell ED, Sajin B, Faissner A, Gotz B, Silver J, Steindler DA (1995) Cell and molecular analysis of the developing and adult mouse subventricular zone of the cerebral hemispheres. J Comp Neurol 361:249–266PubMedCrossRefGoogle Scholar
  22. Husmann K, Faissner A, Schachner M (1992) Tenascin promotes cerebellar granule cell migration and neurite outgrowth by different domains in the fibronectin type III repeats. J Cell Biol 116:1475–1486PubMedCrossRefGoogle Scholar
  23. Jankovski A, Sotelo C (1996) Subventricular zone-olfactory bulb migratory pathway in the adult mouse: cellular composition and specificity as determined by heterochronic and heterotopic transplantation. J Comp Neurol 371:376–396PubMedCrossRefGoogle Scholar
  24. Joester A, Faissner A (1999) Evidence for combinatorial variability of tenascin-C isoforms and developmental regulation in the mouse central nervous system. J Biol Chem 274:17144–17151PubMedCrossRefGoogle Scholar
  25. Joester A, Faissner A (2001) The structure and function of tenascins in the nervous system. Matrix Biol 20:13–22PubMedCrossRefGoogle Scholar
  26. Jones FS, Jones PL (2000a) The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling. Dev Dyn 218:235–259PubMedCrossRefGoogle Scholar
  27. Jones PL, Jones FS (2000b) Tenascin-C in development and disease: gene regulation and cell function. Matrix Biol 19:581–596PubMedCrossRefGoogle Scholar
  28. Laywell ED, Steindler DA (1991) Boundaries and wounds, glia and glycoconjugates. Cellular and molecular analyses of developmental partitions and adult brain lesions. Ann N Y Acad Sci 633:122–141PubMedCrossRefGoogle Scholar
  29. Miragall F, Kadmon G, Faissner A, Antonicek H, Schachner M (1990) Retention of J1/tenascin and the polysialylated form of the neural cell adhesion molecule (N-CAM) in the adult olfactory bulb. J Neurocytol 19:899–914PubMedCrossRefGoogle Scholar
  30. Moritz S, Lehmann S, Faissner A, von Holst A (2008) An induction gene trap screen in neural stem cells reveals an instructive function of the niche and identifies the splicing regulator sam68 as a tenascin-C-regulated target gene. Stem Cells 26:2321–2331PubMedCrossRefGoogle Scholar
  31. Rigato F, Garwood J, Calco V, Heck N, Faivre-Sarrailh C, Faissner A (2002) Tenascin-C promotes neurite outgrowth of embryonic hippocampal neurons through the alternatively spliced fibronectin type III BD domains via activation of the cell adhesion molecule F3/contactin. J Neurosci 22:6596–6609PubMedGoogle Scholar
  32. Taylor J, Pesheva P, Schachner M (1993) Influence of janusin and tenascin on growth cone behavior in vitro. J Neurosci Res 35:347–362PubMedCrossRefGoogle Scholar
  33. Theodosis DT, Pierre K, Cadoret MA, Allard M, Faissner A, Poulain DA (1997) Expression of high levels of the extracellular matrix glycoprotein, tenascin-C, in the normal adult hypothalamoneurohypophysial system. J Comp Neurol 379:386–398PubMedCrossRefGoogle Scholar
  34. von Holst A, Egbers U, Prochiantz A, Faissner A (2007) Neural stem/progenitor cells express 20 tenascin C isoforms that are differentially regulated by Pax6. J Biol Chem 282:9172–9181CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Cell Morphology and Molecular NeurobiologyRuhr UniversityBochumGermany
  2. 2.Département Neurotransmission et Sécrétion Neuroendocrine, Institut des Neurosciences Cellulaires et Intégratives (UPR 3212)Centre National de la Recherche Scientifique et Université de StrasbourgStrasbourgFrance
  3. 3.Université Paris Descartes, INSERM U686, Centre universitaire des Saints-PèresParisFrance

Personalised recommendations