Neurite-Promoting Factors for Spinal Neurons: Their Possible Importance for the Understanding of Amyotrophic Lateral Sclerosis and the Spinal Muscular Atrophies

  • C. E. Henderson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 209)


The nerve growth factor (NGF), identified in 1956 by Cohen and Levi- Montalcini (for review, see ref.[l]), and subsequently sequenced and cloned, is the best-characterized factor affecting nerve growth. The purified protein has three major effects on sympathetic and sensory neurons cultured at appropriate developmental stages: it is required for cell survival, and enhances neurite outgrowth and neurotransmitter synthesis. It is likely that NGF is released by target tissues in order to assure themselves of sufficient sympathetic and sensory innervation. This hypothesis is supported by the observations that: (a) administration of anti-NGF antibodies in new-born mice results in a selective loss of sympathetic neurons, known as ‘immunosympathectomy’[2]; (b) axons of responsive neurons are capable of transporting NGF in a retrograde manner from the nerve terminal to the cell body[3]; and (c) levels of NGF in target organs correlate with the density of sympathetic innervation[4]. NGF, however, has no known action on spinal motor neurons.


Amyotrophic Lateral Sclerosis Motor Neuron Nerve Growth Factor Neurite Outgrowth Spinal Muscular Atrophy 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H. Thoenen, and Y-A. Barde, Physiology of nerve growth factor, Physiol.Rev., 60: 1284–1335 (1980).PubMedGoogle Scholar
  2. 2.
    R. Levi-Montalcini, and B. Booker, Destruction of the sympathetic ganglia in mammals by an antiserum to the nerve-growth promoting factor, Proc.Natl.Acad.Sci.USA., 42: 384–391 (1960).CrossRefGoogle Scholar
  3. 3.
    I. A. Hendry, Control in the development of the vertebrate sympathetic nervous system, Rev.Neurosci., 2: 149–194 (1976).Google Scholar
  4. 4.
    S. Korsching, and H. Thoenen, Nerve growth factor in sympatheticganglia and corresponding target organs of the rat: correlation with density of sympathetic innervation, Proc.Natl.Acad.Sci.USA., 80: 3513–3516 (1983).PubMedCrossRefGoogle Scholar
  5. 5.
    V. Hamburger, Regression versus peripheral control of differentiation in motor hypoplasia, Am.J.Anat., 102: 365–410 (1958).PubMedCrossRefGoogle Scholar
  6. 6.
    M. Hollyday, and V. Hamburger, Reduction of the naturally occurring motor neuron loss by enlargement of the periphery, J.Comp.Neurol., 170: 311–320 (1976).PubMedCrossRefGoogle Scholar
  7. 7.
    J. Lewis, A. Chevallier, M. Kieny, and L. Wolpert, Muscle nerve branches do not develop in chick wings devoid of muscle, J.Embryol.Exp.Morph., 64: 211–232 (1981).PubMedGoogle Scholar
  8. 8.
    M. C. Brown, R. L. Holland, and W. G. Hopkins, Motor nerve sprouting, Ann.Rev.Neurosci., 4: 17–42 (1981).PubMedCrossRefGoogle Scholar
  9. 9.
    L. B. Dribin, and J. N. Barrett, Two components of conditioned medium increase neuritic outgrowth from rat spinal cord explants, J.Neurosci.Res., 8: 271–280 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    H. Tanaka, and K. Obata, Survival and neurite outgrowth of chick embryo spinal cord cells in serum-free culture, Dev.Brain Res., 4: 313–321 (1982).CrossRefGoogle Scholar
  11. 11.
    M. R. Bennett, L. Lai, and V. Nurcombe, Identification of embryonic motor neurons in vitro: their survival is dependent on skeletal muscle, Brain Res., 190: 537–542 (1980).PubMedCrossRefGoogle Scholar
  12. 12.
    A. L. Calof, and L. F. Reichardt, Motor neurons purified by cell sorting respond to two distinct activities in myotube-conditioned medium, Develop.Biol., 106: 194–210 (1984).PubMedCrossRefGoogle Scholar
  13. 13.
    F. M. Longo, M. Manthorpe, and S. Varon, Spinal cord neuronotrophic factors: I - bioassay of schwannoma and other conditioned media, Dev.Brain Res., 3: 277–294 (1982).CrossRefGoogle Scholar
  14. 14.
    E. D. Pollack, W. L. Muhlach, and V. Liebig, Neurotropic influence of mesenchymal limb target tissue on spinal cord neurite growth in vitro, J.Comp.Neurol., 177: 87–112 (1981).Google Scholar
  15. 15.
    E. L. Giller, J. H. Neale, P. N. Bullock, B. K. Schrier, and P. G. Nelson, Choline acetyltransferase activity of spinal cord cell cultures increased by co-culture with muscle and by muscle- conditioned medium, J.Cell Biol., 74: 16–29 (1977).PubMedCrossRefGoogle Scholar
  16. 16.
    C. E. Henderson, M. Huchet, and J. P. Changeux, Neurite outgrowth from embryonic spinal neurons is promoted by media conditioned by muscle cells, Proc.Natl.Acad.Sci.USA., 78: 2625–2629 (1981).PubMedCrossRefGoogle Scholar
  17. 17.
    C. E. Henderson, Roles for retrograde factors in synapse formation at the nerve-muscle junction, Progr.Brain Res., 58: 369–373 (1983).CrossRefGoogle Scholar
  18. 18.
    C. E. Henderson, M. Huchet, and J. P. Changeux, Denervation increases a neurite-promoting activity in extracts of skeletal muscle, Nature (London), 302: 609–611 (1983).CrossRefGoogle Scholar
  19. 19.
    C. E. Henderson, M. Huchet, and J. P. Changeux, Neurite-promoting activities for embryonic spinal neurons and their developmental changes in the chick, Develop.Biol., 104: 336–347 (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    M. E. Gurney, Suppression of terminal sprouting at the neuromuscular junction by immune sera, Nature (London), 307: 546–548 (1984).CrossRefGoogle Scholar
  21. 21.
    M. E. Gurney, and B. Apatoff, Activity of a muscle-derived growth factor for spinal neurons in vitro and in vivo, Soc.Neurosci. Abstr., 10: 1051 (1984).Google Scholar
  22. 22.
    R. W. Gundersen, and K. H. C. Park, The effects of conditioned media on spinal neurites: substrate-associated changes in neurite direction and adherence, Develop.Biol., 104: 18–27 (1984).PubMedCrossRefGoogle Scholar
  23. 23.
    A. D. Lander, D. Fujii, D. Gospadorowicz, and L. F. Reichardt, Characterization of a factor that promotes neurite outgrowth: evidence linking activity to a heparan sulfate proteoglycan, J.Cell Biol., 94: 574–585 (1982).PubMedCrossRefGoogle Scholar
  24. 24.
    T. Ebendal, L. Olson, A. Seiger, and K. O. Hedlund, Nerve growth factors in the rat iris, Nature (London), 286: 25–28 (1980).CrossRefGoogle Scholar
  25. 25.
    D. L. Shelton, and L. F. Reichardt, Expression of the 3-nerve growth factor gene correlates with the density of sympathetic innervation in effector organs, Proc.Natl.Acad.Sci.USA, 81: 7951–7955 (1984).PubMedCrossRefGoogle Scholar
  26. 26.
    M. C. Brown, and R. L. Holland, A central role for denervated tissues in causing nerve sprouting, Nature (London), 282: 724–726 (1979).CrossRefGoogle Scholar
  27. 27.
    R. H. Pittman, and R. W. Oppenheim, Neuromuscular blockade increases motor neurone survival during normal cell death in the chick embryo, Nature (London), 271: 364–366 (1978).CrossRefGoogle Scholar
  28. 28.
    J. R. Slack, and S. Pockett, Motor neurotrophic factor in denervated adult skeletal muscle, Brain Res., 247: 138–140 (1982).PubMedCrossRefGoogle Scholar
  29. 29.
    M. A. Hill, and M. R. Bennett, Cholinergic growth factor from skeletal muscle elevated following denervation, Neurosci.Lett., 35: 31–35 (1983).PubMedCrossRefGoogle Scholar
  30. 30.
    C. E. Henderson, P. Benoit, M. Huchet, J. L. Guénet, and J. P. Changeux, Increase of neurite-promoting activity for spinal neurons in muscles of ‘paralysé’ mice and tenotomized rats, Dev.Brain Res., 25: 65–70 (1986).CrossRefGoogle Scholar
  31. 31.
    S. H. Appel, A unifying hypothesis for the cause of amyotrophic lateral sclerosis, Parkinsonism and Alzheimer Disease, Ann.Neurol., 10: 499–505.Google Scholar
  32. 32.
    M. E. Gurney, A. C. Belton, N. Cashman, and J. P. Antel, Inhibition of terminal axonal sprouting by serum from patients with amyotrophic lateral sclerosis, N.Engl.J.Med., 311: 933–939 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • C. E. Henderson
    • 1
  1. 1.Neurobiologie MoléculaireInstitut PasteurParisFrance

Personalised recommendations