Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor

Abstract

CILIARY neurotrophic factor (CNTF) was originally characterized as a survival factor for chick ciliary neurons in vitro1. More recently, it was shown to promote the survival of a variety of other neuronal cell types2,3 and to affect the differentiation of E7 chick sympathetic neurons by inhibiting their proliferation and by inducing the expression of vasoactive intestinal peptide immunoreac-tivity (VIP-IR) 4. In cultures of dissociated sympathetic neurons from newborn rats, CNTF induces cholinergic differentiation as shown by increased levels of choline acetyltransferase (ChAT) 5. This increase is paralleled by a reduction of tyrosine hydroxylase (TH) activity. Moreover, CNTF promotes the differentiation of bipotential 02A progenitor cells to type-2-astrocytes6in vitro. To help establish which, if any, of these functions CNTF exerts in vivo, it is necessary to determine its primary structure, cellular expression, developmental regulation and localization. The complementary DNA-deduced amino-acid sequence and subsequent expression of cDNA clones covering the entire coding region in HeLa-cells indicate that CNTF is a cytosolic protein. This, together with its regional distribution and its developmental expression, show that CNTF is not a target-derived neurotrophic factor. CNTF thus seems to exhibit neurotrophic and differentiation properties only after becoming available either by cellular lesion or by an unknown release mechanism.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Adler, R., Landa, K., Manthorpe, M. & Varon, S. Science 204, 1434–1436 (1979).

    Article  ADS  CAS  Google Scholar 

  2. Barbin, G., Manthorpe, M. & Varon, S. J. Neurochem. 43, 1468–1478 (1984).

    Article  CAS  Google Scholar 

  3. Manthorpe, M., Skaper, Skaper, S. D., Williams, L. R. & Varon, S. Brain Res. 367, 282–286 (1986).

    Article  CAS  Google Scholar 

  4. Ernsberger, U., Sendtner, M. & Rohrer, H. Neuron 2, 1275–1284 (1989).

    Article  CAS  Google Scholar 

  5. Saadat, S., Sendtner, M. & Rohrer, H. J. Cell Biol. 108, 1807–1816 (1989).

    Article  CAS  Google Scholar 

  6. Hughes, S. M., Lillien, L. E., Raff, M. C., Rohrer, H. & Sendtner, M. Nature 335, 70–73 (1988).

    Article  ADS  CAS  Google Scholar 

  7. Lillien, L. E., Sendtner, M., Rohrer, H., Hughes, S. M. & Raff, M. C. Neuron 1, 485–494 (1988).

    Article  CAS  Google Scholar 

  8. Kozak, M. J. Cell Biol. 108, 229–241 (1989).

    Article  ADS  CAS  Google Scholar 

  9. Leibrock, J. et al. Nature 341, 149–152 (1989).

    Article  ADS  CAS  Google Scholar 

  10. Unsicker, K. et al. Proc. natn. Acad. Sci. U.S.A. 84, 5459–5463 (1987).

    Article  ADS  CAS  Google Scholar 

  11. Schubert, D., LaCorbiere, M. & Esch F. J. Cell Biol. 102, 2295–2301 (1986).

    Article  CAS  Google Scholar 

  12. Abraham, J. A. et al. Science 233, 545–548 (1986).

    Article  ADS  CAS  Google Scholar 

  13. Kostura, M. W. et al. Proc. natn. Acad. Sci. U.S.A. 86, 5227–5231 (1989).

    Article  ADS  CAS  Google Scholar 

  14. McGrath, J. P. & Varshavsky, A. Nature 340, 400–404 (1989).

    Article  ADS  CAS  Google Scholar 

  15. Thoenen, H., Bandtlow, C., & Heumann, R. Rev. Physiol. Biochem. Pharmac. 109, 145–178 (1987).

    Article  CAS  Google Scholar 

  16. Oppenheim, R. W. J. comp. Neurol. 246, 281–286 (1986).

    Article  CAS  Google Scholar 

  17. Johnson, E. M. Jr, Gorin, P. M., Brandeis, L. D. & Pearson, J. Science 210, 916–918 (1980).

    Article  ADS  CAS  Google Scholar 

  18. Eckerskorn, C., Mewes, W., Goretzki, H. & Lottspeich, F. Eur. J. Biochem. 176, 509–519 (1988).

    Article  CAS  Google Scholar 

  19. Tsugita, A., Uchida, T., Mewes, H. W. & Ataka, T. Biochemistry 102, 1593–1597 (1987).

    Article  CAS  Google Scholar 

  20. Spranger, M. et al. Eur. J. Neuroscience (in the press).

  21. Okayama, H. et al. Meth. Enzym. 154, 3–29 (1987).

    Article  CAS  Google Scholar 

  22. Saiki, R. K. et al. Science 239, 487–491 (1988).

    Article  ADS  CAS  Google Scholar 

  23. Sanger, F., Nickel, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 72, 3918–3921 (1979).

    Google Scholar 

  24. Frohmann, M. A., Dush, M. K. & Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 85, 8998–9002 (1988).

    Article  ADS  Google Scholar 

  25. Loh, E. Y., Elliott, J. F., Cwirla, S., Lanier, L. L. & Davies, M. M. Science 243, 217–220 (1989).

    Article  ADS  CAS  Google Scholar 

  26. Spandidos, D. A. & Wilhie N. M. in Transcription and Translation—a Practical Approach (eds Hames B. D. & Higgins, S. J.) 1–48 (IRL Press, Oxford, 1984).

    Google Scholar 

  27. Chomczynski, P. & Sacchi, N. Analyt. Biochem. 162, 156–159 (1987).

    Article  CAS  Google Scholar 

  28. Lindholm, D., Heumann, R., Hengerer, B. & Thoenen, H. J. biol. Chem. 263, 16348–16351 (1988).

    CAS  PubMed  Google Scholar 

  29. Feinberg, A. P. & Vogelstein, B. Analyt. Biochem. 132, 6–13 (1983).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stöckli, K., Lottspeich, F., Sendtner, M. et al. Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 342, 920–923 (1989). https://doi.org/10.1038/342920a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/342920a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing