Advertisement

Cellular and Molecular Neurobiology

, Volume 8, Issue 1, pp 35–40 | Cite as

Nerve growth factor: Cellular localization and regulation of synthesis

  • Hans Thoenen
  • Christine Bandtlow
  • Rolf Heumann
  • Dan Lindholm
  • Michael Meyer
  • Hermann Rohrer
Review

Summary

  1. 1.

    The role of nerve growth factor (NGF) as a retrograde messenger between peripheral target tissues and innervating sympathetic and neural crest-derived sensory neurons is supported by the observations that (a) the interruption of retrograde axonal transport has the same effects as the neutralization of endogenous NGF by anti-NGF antibodies and (b) the close correlation between the density of innervation by fibers of NGF-responsive neurons and the levels of NGF and mRNANGF in their target organs.

     
  2. 2.

    In situ hybridization experiments have demonstrated that a great variety of cells in the projection field or NGF-responsive neurons is synthesizing NGF, among them epithelial cells, smooth muscle cells, fibroblasts, and Schwann cells.

     
  3. 3.

    The temporal correlation between the growth of trigeminal sensory fibers into the whisker pad of the mouse and the commencement of NGF synthesis initially suggested a causal relationship between these two events. However, in chick embryos rendered aneural by prior removal of the neural tube or the neural crest, it was shown that the onset of NGF synthesis in the periphery is independent of neurons, and is controlled by an endogenous “clock” whose regulatory mechanism remains to be established.

     
  4. 4.

    A comparison between NGF synthesis in the nonneuronal cells of the newborn rat sciatic nerve and that in the adult sciatic nerve after lesion provided evidence for the important regulatory role played by a secretory product of activated macrophages. The identity of this product is currently under investigation.

     

Key words

nerve growth factor neural crest sympathetic system axonal transport in situ hybridization 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bandtlow, C. E., Heumann, R., Schwab, M. E., and Thoenen, H. (1987). Cellular localization of nerve growth factor synthesis byin situ hybridization.EMBO J. 6891–899.PubMedGoogle Scholar
  2. Barde, Y.-A., Davies, A. M., Johnson, J. E., Lindsay, R. M., and Thoenen, H. (1987). Brain derived neurotrophic factor.Prog. Brain Res. 71 185–189.PubMedCrossRefGoogle Scholar
  3. Barth, E. M. Korsching, S., and Thoenen, H. (1984). Regulation of nerve growth factor synthesis and release in organ cultures of rat iris.J. Cell Biol. 99839–843.PubMedCrossRefGoogle Scholar
  4. Cowan, W. M., Fawcett, J. W., O'Leary, D. D. M., and Stanfield, B. B. (1984). Regressive Events in Neurogenesis.Science 2251258–1265.PubMedCrossRefGoogle Scholar
  5. Davies, A., and Lumsden, A. (1984). Relation of target encounter and neuronal death to nerve growth factor responsiveness in the developing mouse trigeminal ganglion.J. Comp. Neurol. 223124–137.PubMedCrossRefGoogle Scholar
  6. Davies, A. M., Bandtlow, C., Heumann, R., Korsching, S., Rohrer, H., and Thoenen, H. (1987). Timing and site of nerve growth factor synthesis in developing skin in relation to its innervation and expression of the receptor.Nature 326353–358.PubMedCrossRefGoogle Scholar
  7. Greene, L. A., and Shooter, E. M. (1980). The nerve growth factor: Biochemistry, synthesis, and mechanism of action.Ann. Rev. Neurosci. 3353–402.PubMedCrossRefGoogle Scholar
  8. Heumann, R., and Thoenen, H. (1986). Comparison between the time course of changes in nerve growth factor (NGF) protein levels and those of its messenger RNA in the cultured rat iris.J. Biol. Chem. 2619246–9249.PubMedGoogle Scholar
  9. Heumann, R., Korsching, S., Scott, J., and Thoenen, H. (1984). Relationship between levels of nerve growth factor (NGF) and its messenger RNA in sympathetic ganglia and peripheral target tissues.EMBO J. 33138–3189.Google Scholar
  10. Heumann, R., Korsching, S., Bandtlow, C., and Thoenen, H. (1987). Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection.J. Cell Biol. 1041623–1631.PubMedCrossRefGoogle Scholar
  11. Korsching, S. (1987). The role of nerve growth factor in the CNS.TINS 12570–573.Google Scholar
  12. Korsching, S., and Thoenen, H. (1983a). Nerve growth factor in sympathetic ganglia and corresponding target organs of the rat: Correlation with density of sympathetic innervation.Proc. Natl. Acad. Sci. USA 803513–3516.PubMedCrossRefGoogle Scholar
  13. Korsching, S., and Thoenen, H. (1983b). Quantitative demonstration of the retrograde axonal transport of endogenous nerve growth factor.Neurosci. Lett. 391–4.PubMedCrossRefGoogle Scholar
  14. Levi-Montalcini, R., and Angeletti, P. U. (1968). Nerve growth factor.Physiol. Rev. 48534–569.PubMedGoogle Scholar
  15. Schwab, M. E., and Thoenen, H. (1983). Retrograde axonal transport. InHandbook of Neurochemistry Vol. 5 (A. Lajtha, Ed.), Plenum, New York, London, pp. 381–404.Google Scholar
  16. Shelton, D. L., and Reichardt, L. F. (1984). Expression of the nerve growth factor gene correlates with the density of sympathetic innervation in effector organs.Proc. Natl. Acad. Sci. USA 817951–7955.PubMedCrossRefGoogle Scholar
  17. Shelton, D. L., and Reichardt, L. F. (1986). Studies on the regulation of beta-nerve growth factor gene expression in the rat iris: The level of mRNA-encoding nerve growth factor is increased in irises placed in explant cultures in vitro, but not in irises deprived of sensory or sympathetic innervation in vivo.J. Cell Biol. 1021940–1948.PubMedCrossRefGoogle Scholar
  18. Thoenen, H., and Barde, Y. A. (1980). Physiology of nerve growth factor.Physiol. Rev. 601284–1335.PubMedGoogle Scholar
  19. Thoenen, H., and Edgar, D. (1985). Neurotrophic factors.Science 229238–242.PubMedCrossRefGoogle Scholar
  20. Thoenen, H., Bandtlow, C., and Heumann, R. (1987). The physiological function of nerve growth factor in the central nervous system: Comparison with the periphery.Rev. Physiol. Biochem. Pharmacol. 109145–178.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • Hans Thoenen
    • 1
  • Christine Bandtlow
    • 1
  • Rolf Heumann
    • 1
  • Dan Lindholm
    • 1
  • Michael Meyer
    • 1
  • Hermann Rohrer
    • 1
  1. 1.Department of NeurochemistryMax-Planck-Institute for PsychiatryMartinsriedFRG

Personalised recommendations