Steps in Establishing a Biological Relevance for Glia-Derived Nexin

  • Denis Monard
  • Eva Reinhard
  • Roland Meier
  • Juerg Sommer
  • Lynne Farmer
  • Giorgio Rovelli
  • Rainer Ortmann
Part of the NATO ASI Series book series (NSSA, volume 191)


The development and maintenance of the nervous system requires a multiplicity of interactions between the neuroblast and the neuron and their respective environments. After a phase of cellular migration, the first step in the differentiation program of the neuroblast is to extend neurites which will become either dendrites capable of receiving information from the afferent cells or axons which will establish contact with specific targets in order to propagate this information. Today, neurite outgrowth is considered to be a complex phenomenon which can be influenced by many different molecules. Neurotrophic factors, neurotransmitters, and components of the extracellular matrix trigger or modulate this event in vitro and, in some cases, in vivo.1–6 Some of the same molecules are probably also involved in the regenerative events whereby neurite outgrowth is reinitiated following a lesion.


Nerve Growth Factor Sciatic Nerve Neurite Outgrowth Olfactory System Promote Neurite Outgrowth 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    H. Thoenen, and D. Edgar, Neurotrophic factors. Science 229: 238 (1985).CrossRefPubMedGoogle Scholar
  2. 2.
    D. Bray, Growth cones: do they pull or are they pushed? TINS 10: 431 (1987).Google Scholar
  3. 3.
    Y. Dodd, and T.M. Jessell, Axon guidance and the patterning of neuronal projections in vertebrates. Science 242: 692 (1988).CrossRefPubMedGoogle Scholar
  4. 4.
    Y.A. Barde, Trophic factors and neuronal survival. Neuron 2: 1525 (1989).CrossRefPubMedGoogle Scholar
  5. 5.
    S. Carbonetto, The extracellular matrix of the nervous system. TINS 7: 382 (1984).Google Scholar
  6. 6.
    D. Monard, Cell-derived proteases and protease inhibitors as regulators of neurite outgrowth. TINS 11: 541 (1988).Google Scholar
  7. 7.
    R.P. Skoff, D.L. Price, and A. Stocks, Electron microscopic autoradiographic studies of gliogenesis in rat optic nerve. I. Cell proliferation. J. Comp. Neurol. 169: 291 (1976).CrossRefPubMedGoogle Scholar
  8. 8.
    J.L. Salzar, and R.P. Bunge, Studies of Schwann cell proliferation. J. Cell Biol. 84: 739 (1980).CrossRefGoogle Scholar
  9. 9.
    M.E. Hatten, and CA. Mason, Neuron-astroglia interactions in vitro and in vivo. TINS 9: 168 (1986).Google Scholar
  10. 10.
    D. Monard, F. Solomon, M. Rentsch et al., Glia-induced morphological differentiation in neuroblastoma cells. Proc. Natl. Acad. Sci. USA 70: 1894 (1973).CrossRefPubMedGoogle Scholar
  11. 11.
    Y. Schurch-Rathgeb, and D. Monard, Brain development influences the appearance of glial factor-like activity in rat brain primary cultures. Nature 273: 308 (1978).CrossRefPubMedGoogle Scholar
  12. 12.
    D. Monard, K. Stockel, R. Goodman et al., Distinction between nerve growth factor and glial factor. Nature 258: 444 (1975).CrossRefPubMedGoogle Scholar
  13. 13.
    D. Monard, E. Niday, A. Limat et al., Inhibition of protease activity can lead to neurite extension in neuroblastoma cells. Prog. Brain Res. 58: 359 (1983).CrossRefPubMedGoogle Scholar
  14. 14.
    J. Guenther, H. Nick, and D. Monard, A glia-derived neurite-promoting factor with protease inhibitory activity. EMBO J. 4: 1963 (1985).Google Scholar
  15. 15.
    S.R. Stone, H. Nick, J. Hofsteenge et al., Glia-derived neurite-promoting factor is a slow-binding inhibitor of trypsin, thrombin, and urokinase. Arch. Biochem. Biophys. 252: 237 (1987).CrossRefPubMedGoogle Scholar
  16. 16.
    A. Wallace, G. Rovelli, J. Hofsteenge et al., Effect of heparin on the glia-derived-nexin-thrombin interaction. Biochem. J. 257: 191 (1989).PubMedGoogle Scholar
  17. 17.
    J. Sommer, S.M. Gloor, G.F. Rovelli et al., cDNA sequence coding for a rat glia-derived nexin and its homology to members of the serpin super family. Biochemistry 26: 6407 (1987).CrossRefPubMedGoogle Scholar
  18. 18.
    S. Gloor, K. Odink, J. Guenther et al., A glia-derived neurite promoting factor with protease inhibitory activity belongs to protease nexins. Cell 47: 687 (1986).CrossRefPubMedGoogle Scholar
  19. 19.
    H. Loebermann, R. Tokuoka, J. Deisenhofer et al., Human a1 proteinase inhibitor. J. Mol. Biol. 177: 531 (1984).Google Scholar
  20. 20.
    R. Carrell, and J. Travis, Qt-Antitrypsin and the serpins: variation and countervariation. Trends Biochem. Sci. 10: 20 (1985).CrossRefGoogle Scholar
  21. 21.
    R.W. Scott, B.L. Bergman, A. Bajpai et al., Protease nexin. J. Biol. Chem. 260: 7029 (1985).PubMedGoogle Scholar
  22. 22.
    M. McGrogan, J. Kennedy, M. Ping Li et al., Molecular cloning and expression of two forms of human protease nexin I. Biotechnology 6: 172 (1988).CrossRefGoogle Scholar
  23. 23.
    A.D. Zum, H. Nick, and D. Monard, A glia-derived nexin promotes neurite outgrowth in cultured chick sympathetic neurons. Dey. Neurosci. 10: 17 (1988).CrossRefGoogle Scholar
  24. 24.
    L. Farmer, J. Sommer, and D. Monard, Glia-derived nexin potentiates neurite extension in hippocampal pyramidal cells in vitro. Dey. Neuroscience. In press.Google Scholar
  25. 25.
    D. Gurwitz, and D.D. Cunningham Thrombin modulates and reverses neuroblastoma neurite outgrowth. Proc. Natl. Acad. Sci. USA 85: 3440 (1988).CrossRefPubMedGoogle Scholar
  26. 26.
    E. Reinhard, R. Meier, W. Halfter et al., Detection of glia-derived nexin in the olfactory system of the rat. Neuron 1: 387 (1988).CrossRefPubMedGoogle Scholar
  27. 27.
    R. Heumann, S. Korsching, C. Bandtlow et al., Changes of nerve growth factor synthesis in non-neuronal cells in response to sciatic nerve transection. J. Cell Biol. 104: 1623 (1987).CrossRefPubMedGoogle Scholar
  28. 28.
    R. Meier, P. Spreyer, R. Ortmann et al., Glia-derived nexin, a serine protease inhibitor with neurite promoting activity, is induced after lesion of a peripheral nerve. Nature. In press.Google Scholar
  29. 29.
    S.L. Wagner, J.W. Geddes, C.W. Cotman et al., Protease nexin-I, an antithrombin with neurite outgrowth activity, is reduced in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 86: 8284 (1989).CrossRefPubMedGoogle Scholar
  30. 30.
    G. Rovelli, K.T. Preissner, and D. Monard, Specific interaction of vitronectin with the cell-secreted protease inhibitor glia-derived nexin (GDN) and the GDN-thrombin complex. Submitted for publication.Google Scholar
  31. 31.
    J. Sommer, B. Meyhack, G. Rovelli et al., Expression of glia-derived nexin in yeast. Gene. In press.Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Denis Monard
    • 1
  • Eva Reinhard
    • 1
  • Roland Meier
    • 1
  • Juerg Sommer
    • 1
  • Lynne Farmer
    • 1
  • Giorgio Rovelli
    • 1
  • Rainer Ortmann
    • 1
  1. 1.Friedrich Miescher-InstitutBaselSwitzerland

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