Skip to main content
SpringerLink
Log in

Cell Type- and Isotype-Specific Expression and Regulation of β-Tubulins in Primary Olfactory Ensheathing Cells and Schwann Cells In Vitro

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Olfactory ensheathing cells (OECs) and Schwann cells (SCs) are closely-related cell types with regeneration-promoting properties. Comparative gene expression analysis is particularly relevant since it may explain cell type-specific effects and guide the use of each cell type into special clinical applications. In the present study, we focused on β-tubulin isotype expression in primary adult canine glia as a translational large animal model. β-tubulins so far have been studied mainly in non-neuronal tumors and implied in tumorigenic growth. We show here that primary OECs and SCs expressed βII–V isotype mRNA. Interestingly, βIII-tubulin mRNA and protein expression was high in OECs and low in SCs, while fibroblast growth factor-2 (FGF-2) induced its down-regulation in both cell types to the same extent. This was in contrast to βV-tubulin mRNA which was similarly expressed in both cell types and unaltered by FGF-2. Immunocytochemical analysis revealed that OEC cultures contained a higher percentage of βIII-tubulin-positive cells compared to SC cultures. Addition of FGF-2 reduced the number of βIII-tubulin-positive cells in both cultures and significantly increased the percentage of cells with a multipolar morphology. Taken together, we demonstrate cell type-specific expression (βIII) and isotype-specific regulation (βIII, βV) of β-tubulin isotypes in OECs and SCs. While differential expression of βIII-tubulin in primary glial cell types with identical proliferative behaviour argues for novel functions unrelated to tumorigenic growth, strong βIII-tubulin expression in OECs may help to explain the specific properties of this glial cell type.

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

Similar content being viewed by others

References

  1. Barnett SC, Riddell JS (2007) Olfactory ensheathing cell transplantation as a strategy for spinal cord repair—what can it achieve? Nat Clin Pract Neurol 3:152–161

    Article  PubMed  Google Scholar 

  2. Wewetzer K, Verdú E, Angelov DN, Navarro X (2002) Olfactory ensheathing glia and Schwann cells: two of a kind? Cell Tissue Res 309:337–345

    Article  PubMed  Google Scholar 

  3. Franklin RJ, Barnett SC (1997) Do olfactory glia have advantages over Schwann cells for CNS repair? J Neurosci Res 50:665–672

    Article  PubMed  CAS  Google Scholar 

  4. Franssen EF, de Bree FM, Essing AHW, Ramón-Cueto A, Verhaagen J (2008) Comparative gene expression profiling of olfactory ensheathing glia and Schwann cells indicate distinct tissue repair characteristics of olfactory ensheathing glia. Glia 56:1285–1298

    Article  PubMed  Google Scholar 

  5. Guérout N, Derambure C, Drouot L, Bon-Mardion N, Duclos C, Boyer O, Marie JP (2010) Comparative gene expression profiling of olfactory ensheathing cells from olfactory bulb and olfactory mucosa. Glia 58:1570–1580

    PubMed  Google Scholar 

  6. Roet KC, Bossers K, Franssen EH, Ruitenberg MJ, Verhaagen J (2011) A meta-analysis of microarray-based gene expression studies of olfactory bulb-derived olfactory ensheathing cells. Exp Neurol 229:10–45

    Article  PubMed  CAS  Google Scholar 

  7. Vukovic J, Ruitenberg MJ, Roet K, Franssen E, Arulpragasam A, Sasaki T, Verhaagen J, Harvey AR, Busfield SJ, Plant GW (2009) The glycoprotein fibulin-3 regulates morphology and motility of olfactory ensheathing cells in vitro. Glia 57:424–443

    Article  PubMed  Google Scholar 

  8. Jeffery ND, Hamilton L, Granger N (2011) Designing clinical trials in canine spinal cord injury as a model to translate successful laboratory interventions into clinical practice. Vet Rec 168:102–107

    Article  PubMed  CAS  Google Scholar 

  9. Schneider MR, Wolf E, Braun J, Kolb HJ, Adler H (2008) Canine embryo-derived stem cells and models for human diseases. Hum Mol Genet 17(R1):R42–R47

    Article  PubMed  CAS  Google Scholar 

  10. Wewetzer K, Radtke C, Kocsis JD, Baumgärtner W (2011) Species-specific control of cellular proliferation and the impact of large animal models for the use of olfactory ensheathing cells and Schwann cells in spinal cord repair. Exp Neurol 229:80–87

    Article  PubMed  Google Scholar 

  11. Sonigra RJ, Kandiah SS, Wigley CB (1996) Spontaneous immortalisation of ensheathing cells from adult rat olfactory nerve. Glia 16:247–256

    Article  PubMed  CAS  Google Scholar 

  12. Sonigra RJ, Brighton PC, Jacoby J, Hall S, Wigley CB (1999) Adult rat olfactory nerve ensheathing cells are effective promoters of adult central nervous system neurite outgrowth in coculture. Glia 25:256–269

    Article  PubMed  CAS  Google Scholar 

  13. Nogales E (2001) Structural insight into microtubule function. Annu Rev Biophys Biomol Struct 30:397–420

    Article  PubMed  CAS  Google Scholar 

  14. Hammond JW, Cai D, Verhey KJ (2008) Tubulin modifications and their cellular functions. Curr Opin Cell Biol 20:71–76

    Article  PubMed  CAS  Google Scholar 

  15. Katsetos CD, Legido A, Perentes E, Mörk SJ (2003) Class III beta-tubulin isotype: a key cytoskeletal protein at the crossroads of developmental neurobiology and tumor neuropathology. J Child Neurol 12:851–866

    Article  Google Scholar 

  16. Hiser L, Aggarwal A, Young R, Frankfurter A, Spano A, Correia JJ, Lobert S (2006) Comparison of beta-tubulin mRNA and protein levels in 12 human cancer cell lines. Cell Motil Cytoskelet 63:41–52

    Article  PubMed  CAS  Google Scholar 

  17. Leandro-García LJ, Leskelä S, Landa I, Montero-Conde C, López-Jiménez E, Letón R, Cascón A, Robledo M, Rodríguez-Antona C (2010) Tumoral and tissue-specific expression of the major human beta-tubulin isotypes. Cytoskeleton 67:214–223

    Article  PubMed  Google Scholar 

  18. Lobert S, Hiser L, Correia JJ (2010) Expression profiling of tubulin isotypes and microtubule-interacting proteins using real-time polymerase chain reaction. Methods Cell Biol 95:47–58

    Article  PubMed  CAS  Google Scholar 

  19. Bock P, Beineke A, Techangamsuwan S, Baumgärtner W, Wewetzer K (2007) Differential expression of HNK-1 and p75(NTR) in adult canine Schwann cells and olfactory ensheathing cells in situ but not in vitro. J Comp Neurol 505:572–585

    Article  PubMed  Google Scholar 

  20. Techangamsuwan S, Imbschweiler I, Kreutzer R, Kreutzer M, Baumgärtner W, Wewetzer K (2008) Similar behaviour and primate-like properties of adult canine Schwann cells and olfactory ensheathing cells in long-term culture. Brain Res 1240:31–38

    Article  PubMed  CAS  Google Scholar 

  21. Wewetzer K, Kern N, Ebel C, Radtke C, Brandes G (2005) Phagocytosis of O4+ axonal fragments in vitro by p75− neonatal rat olfactory ensheathing cells. Glia 49:577–587

    Article  PubMed  Google Scholar 

  22. Omar M, Bock P, Kreutzer R, Ziege S, Imbschweiler I, Hansmann F, Peck C-T, Baumgärtner W, Wewetzer K (2011) Defining the morphological phenotype: 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) is a novel marker for in situ detection of canine but not rat olfactory ensheathing cells. Cell Tissue Res 344:391–405

    Article  PubMed  CAS  Google Scholar 

  23. Kreutzer R, Kreutzer M, Pröpsting MJ, Sewell AC, Leeb T, Naim HY, Baumgärtner W (2008) Insights into post-translational processing of beta-galactosidase in an animal model resembling late infantile human G-gangliosidosis. J Cell Mol Med 12:1661–1671

    Article  PubMed  CAS  Google Scholar 

  24. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:RESEARCH0034

    Article  PubMed  Google Scholar 

  25. Bhattacharya B, Frankfurter A, Cabral F (2008) A minor beta-tubulin essential for mammalian cell proliferation. Cell Motil Cytoskelet 65:708–720

    Article  PubMed  CAS  Google Scholar 

  26. Kelly BM, Gillespie CS, Sherman DL, Brophy PJ (1992) Schwann cells of the myelin-forming phenotype express neurofilament protein NF-M. J Cell Biol 118:397–410

    Article  PubMed  CAS  Google Scholar 

  27. Roberson MD, Toews AD, Goodrum JF, Morell P (1992) Neurofilament and tubulin mRNA expression in Schwann cells. J Neurosci Res 33:156–162

    Article  PubMed  CAS  Google Scholar 

  28. Sotelo-Silveira JR, Calliari A, Kun A, Benech JC, Sanguinetti C, Chalar C, Sotelo JR (2000) Neurofilament mRNAs are present and translated in the normal and severed sciatic nerve. J Neurosci Res 62:65–74

    Article  PubMed  CAS  Google Scholar 

  29. Brandes G, Khayami M, Peck C-T, Baumgärtner W, Bugday H, Wewetzer K (2011) Cell surface expression of 27C7 by neonatal rat olfactory ensheathing cells in situ and in vitro is independent of axonal contact. Histochem Cell Biol 135:397–408

    Article  PubMed  CAS  Google Scholar 

  30. Deng C, Gorrie C, Hayward I, Elston B, Venn M, Mackay-Sim A, Waite P (2006) Survival and migration of human and rat olfactory ensheathing cells in intact and injured spinal cord. J Neurosci Res 83:1201–1212

    Article  PubMed  CAS  Google Scholar 

  31. Ekberg JA, Amaya D, Mackay-Sim A, St John JA (2012) The migration of olfactory ensheathing cells during development and regeneration. Neurosignals 20:147–158

    Article  PubMed  CAS  Google Scholar 

  32. Lankford KL, Sasaki M, Radtke C, Kocsis JD (2008) Olfactory ensheathing cells exhibit unique migratory, phagocytic, and myelinating properties in the X-irradiated spinal cord not shared by Schwann cells. Glia 56:1664–1678

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant to K.W. (BA 815/9-1) from the German Research Foundation. We thank K. Rohn (Department of Biometry and Epidemiology and Information processing, University of Veterinary Medicine, Hannover, Germany) for help with the statistical analysis.

Conflict of interest

The authors disclose any potential sources of conflict of interest.

Author information

Authors and Affiliations

  1. Department of Functional and Applied Anatomy, Center of Anatomy, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany

    Mohamed Omar & Konstantin Wewetzer

  2. Department of Pathology, University of Veterinary Medicine, 30559, Hannover, Germany

    Florian Hansmann, Robert Kreutzer & Mihaela Kreutzer

  3. Center of Systems Neuroscience, 30559, Hannover, Germany

    Florian Hansmann, Mihaela Kreutzer & Konstantin Wewetzer

  4. Department of Cell Biology, Hannover Medical School, Center of Anatomy, 30625, Hannover, Germany

    Gudrun Brandes

  5. Trauma Department, Hannover Medical School, Carl-Neuberg-Str.1, 30625, Hannover, Germany

    Mohamed Omar

Authors
  1. Mohamed Omar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Florian Hansmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Kreutzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mihaela Kreutzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gudrun Brandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Konstantin Wewetzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Konstantin Wewetzer.

Additional information

Mohamed Omar and Florian Hansmann: contributed equally to the study and are thus both considered first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Omar, M., Hansmann, F., Kreutzer, R. et al. Cell Type- and Isotype-Specific Expression and Regulation of β-Tubulins in Primary Olfactory Ensheathing Cells and Schwann Cells In Vitro. Neurochem Res 38, 981–988 (2013). https://doi.org/10.1007/s11064-013-1006-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-013-1006-3

Keywords

Search

Navigation