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A ciliary neuronotrophic factor from peripheral nerve and smooth muscle which is not retrogradely transported

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Abstract

We have found that a CNTF-like molecule which supports ciliary and sympathetic neurons is not retrogradely transported in either sympathetic or parasympathetic nerves. The factor has an apparent Mr of 21 kDa, a pI of 4.9, and is present in peripheral nerves and smooth muscle of the chick. Our experiments indicate that CNTF-like activity does not accumulate on the distal side of ligated chickexpansor nerves. In contrast, there is a clear accumulation of NGF. The activity further differs from NGF in that it is not removed from a smooth muscle of the chick wing by innervating sympathetic fibers. Transection of these fibers does not lead to an accumulation of ciliary activity in theexpansor secundariorum muscle, suggesting that neurons do not actively deplete the muscle of factor by retrograde transport. Finally, recombinant CNTF or semi-purified preparations of CNTF-like activity labelled with125I were not transported to the ciliary ganglion of chicks following injection of biologically active material into the eye. Our results suggest either that endogenous CNTF does not act as a survival factorin vivo, or that retrograde transport is not a property inherent to all neuronotrophic molecules.

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References

  1. Hendery, I. A., Bonyhady, R. E., and Hill, C. E. 1983. The role of target tissues in development and regeneration-retrophins. Birth Defects. 19:263–276.

    Google Scholar 

  2. Hendry, I. A., and Hill, C. E. 1980. Retrograde axonal transport of target tissue derived macromolecules. Nature 287:647–649.

    Google Scholar 

  3. Hamburger, V., and Oppenheim, R. W., 1982. Naturally occurring neuronal death in vertebrates Neurosci. Comm. 1:39–55.

    Google Scholar 

  4. Hendry, I. A., Stach, R., and Herrup, K. 1974. Characteristics of the retrograde axonal transport system for Nerve Growth Factor in the sympathetic nervous system. Brain Res. 82:117–128.

    Google Scholar 

  5. Abrahamson, I. K., Bridges, D., and Rush, R. A. 1987. Transport of endogenous Nerve Growth Factor in the proximal stump of sectioned nerves. J. Neurocytol. 16:417–422.

    Google Scholar 

  6. Korsching, S., and Thoenen, H. 1983. Quantitative demonstration of the retrograde axonal transport of endogenous nerve growth factor. Neurosci. Lett. 39:1–4.

    Google Scholar 

  7. Cowan, W. M., Fawcett, J. W., O'Leary, D. D., and Stanfield, B. B. 1984. Regressive events in neurogenesis. Science 225:1258–1265.

    Google Scholar 

  8. Oppenheim, R. W. 1981. Neuronal cell death and some related regressive phenomena during neurogenesis. Pages 74–133,in Cowan, W. M. (ed), Studies in developmental neurobiology, Oxford University Press, New York.

    Google Scholar 

  9. Gunderson, R. W. 1985. Sensory neurite growth cone guidance by substrate adsorbed Nerve Growth Factor. J. Neurosci. Res. 13:199–212.

    Google Scholar 

  10. Carnow, T. B., Manthorpe, M., Davis, G. E., and Varon, S. 1985. Localized survival of ciliary ganglionic neurons identifies neuronotrophic factor bands on nitrocellulose blots. J. Neurosci. 5:1965–1971.

    Google Scholar 

  11. Rudge, J. S., Davis, G. E., Manthorpe, M., and Varon, S. 1987. An examination of ciliary neuronotrophic factors from avian and rodent tissue extracts using a blot and culture technique. Brain Res. 429:103–110.

    Google Scholar 

  12. Otto, D., Unsicker, K., and Grothe, C. 1987. Pharmacological effects of Nerve Growth Factor and Fibroblast Growth Factor applied to the transectioned sciatic nerve on neuron death in adult rat dorsal root ganglia. Neurosci. Lett. 83:156–160.

    Google Scholar 

  13. Ferguson, I. A., Schweitzer, J. B., and Johnson, E. M. 1990. Basic fibroblast growth factor: receptor-mediated internatlization, metabolism, and anterograde axonal transport in retinal ganglion cells. J. Neurosci. In Press.

  14. Unsicker, K., Reichert-Preibsch, H., Schmidt, R., Pettmann, B., Labourdette, G., and Sensenbrenner, M. 1987. Astroglial fibroblast growth factors have neurotrophic functions for cultured peripheral and central nervous system neurons. Proc. Natl. Acad. Sci. USA. 84:5459–5463.

    Google Scholar 

  15. Belford, D. A., and Rush, R. A. 1983. A survival factor for sympathetic neurons from avian smooth muscle. Brain Res. 282:304–37.

    Google Scholar 

  16. Barbin, G., Manthorpe, M., and Varon. S. 1984 Purification of the chick eye ciliary neuronotrophic factor. J. Neurochem. 43:1468–1478.

    Google Scholar 

  17. Manthorpe, M., Skaper, S. D., Williams, L. R., and Varon, S. 1986. Purification of adult rat sciatic nerve ciliary neuronotrophic factor. Brain Res. 367:282–286.

    Google Scholar 

  18. Varon, S. 1985. Factors promoting the growth of the nervous system. Discussions in Neurosciences 2(3):9–61.

    Google Scholar 

  19. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein dye binding. Anal. Biochem. 72:248–254.

    Google Scholar 

  20. Ferguson, I. A., Williams, R., and Rush, R. A. 1989. Chicken NGF and non-NGF trophic factor synthesis and release by sciatic nerves in vitro. J. Neurosci. Res. 22:408–417.

    Google Scholar 

  21. Collins, F. 1978. Axon initiation by ciliary neurons in culture. Dev. Biol. 65:50–57.

    Google Scholar 

  22. Adler, R., Landa, K. B., Manthorpe, M., and Varon, S. 1979. Cholinergic neuronotrophic factors: intraocular distribution of trophic activity for ciliary neurons. Science 204:1434–1436.

    Google Scholar 

  23. Laemmli, U. K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685.

    Google Scholar 

  24. Collins, F. 1985. Electrophoretic similarity of the ciliary ganglion survival factors from different tissues and species. Dev. Biol. 109:255–258.

    Google Scholar 

  25. Hager, D. A., and Burgess, R. R. 1980. Elution of proteins from sodium dodecyl sulfate polyacrylamide gels, removal of sodium dodecyl sulfate, and renaturation of enzymatic activity: Result with sigma subunit of escherichia coli RNA polymerase, wheat germ DNA topoisomerase, and other enzymes. Anal. Biochem. 109:76–86.

    Google Scholar 

  26. Greenwood, F. C., Hunter, W. M., and Glover, J. S. 1963. Preparation of131I-labelled human growth hormone of high specific radioactivity. Biochem. J. 89:114–123.

    Google Scholar 

  27. Lees, G., Chubb, I., Freeman, C., Geffen, L., and Rush, R. A. 1981. Effect of nerve activity on transport of Nerve Growth Factor and dopamine B-hydroxylase antibodies in sympathetic neurones. Brain Res. 214:186–189.

    Google Scholar 

  28. Bolton, A. F., and Hunter, W. M. 1973. The labelling of proteins to high specific radioactivities by conjugation to a125I-containing acylating agent. Biochem. J. 133:529–539.

    Google Scholar 

  29. Manthorpe, M., Barbin, G., and Varon, S. 1982. Isoelectric focusing of the chick eye ciliary neuronotrophic factor. J. Neurosci. Res. 8:233–239.

    Google Scholar 

  30. Manthorpe, M., Skaper, S., Adler, R., Landa, K., and Varon, S. 1980. Cholinergic neuronotrophic factors: fractionation properties of an extract from selected chick embryonic eye tissues. J. Neurochem. 34:69–75.

    Google Scholar 

  31. Stockli, K. A., Lottspeich, F., Sendtner, M., Masiakowski, P., Carroll, P., Gotz, R., Lindholm, D., and Thoenen, H. 1989. Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 342:920–923.

    Google Scholar 

  32. Morrison, R. S. 1987. Fibroblast Growth Factors: Potential neurotrophic agents in the central nervous system. J. Neurosci. Res. 17:99–101.

    Google Scholar 

  33. Watters, D., and Hendry, I. A. 1985. Purification of a neurotrophic factor for ciliary neurones from chick introcular tissues using non-denaturing conditions. Biochem. Int. 11:245–253.

    Google Scholar 

  34. Abrahamson, I. K., Wilson, P. A., and Rush, R. A. 1986. Production and transport of endogenous trophic activity in a peripheral nerve following target removal. Dev. Brain Res. 27:117–126.

    Google Scholar 

  35. Korsching, S., and Thoenen, H. 1988. Developmental changes of nerve growth factor levels in sympathetic ganglia and their target organs. Dev. Biol. 126:40–46.

    Google Scholar 

  36. Rush, R. A., Abrahamson, I. K., Murdoch, S. Y., Renton, F. J., and Wilson, P. A. 1986. Increase in neuronotrophic activity during the period of smooth muscle innervation. Int. J. Dev. Neurosci. 4:483–492.

    Google Scholar 

  37. 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 innervation and expression of the receptor. Nature 326:353–358.

    Google Scholar 

  38. Heumann, R., and Thoenen, H. 1986. Comparison between the time course of changes in nerve growth factor protein levels and those of its messenger RNA in the cultured rat iris. J. Biol. Chem. 261:9246–9249.

    Google Scholar 

  39. Korsching, S., Heumann, R., Thoenen, H., and Hefti, F. 1986. Cholinergic denervation of the rat hippocampus by fimbrial transection leads to a transient accumulation of nerve growth factor (NGF) without change in mRNANGF content. Neurosci. Lett. 66:175–180.

    Google Scholar 

  40. Ebendal, T., Stromberg, I., Olson, L., and Seiger, A. 1985. Parasympathetic neurotrophic activity in the rat iris: determination after different denervations. Neurosci. 16:181–185.

    Google Scholar 

  41. Lin, L. F., Mismer, D., Lile, J. D., Armes, L. G., Butler, E. T., III., Vannice, J. L., and Collins, F. 1989. Purification, cloning, and expression of ciliary neurotrophic factor (CNTF). Science 246:1023–1025.

    Google Scholar 

  42. Creedon, D. J., and Tuttle, J. B. 1988. Cultured smooth muscle targets lack survival activity for ciliary ganglion neurons. J. Neurosci. 8:3100–3110.

    Google Scholar 

  43. Wentzek, L. A. F., Bowers, C. W., Oliva, E. D., and Pilar, G. 1989. Intact smooth muscle cell preparations secrete trophic factors that support dissociated ciliary neurons in vitro. Soc. Neurosci. Abstr. 15(2):709–709.

    Google Scholar 

  44. Johnson, E. M., Gorin, P. M., Brandeis, L. D., and Pearson, J. 1980. Dorsal root ganglion neurons are destroyed by exposure in utero to maternal antibodies to Nerve Growth Factor. Science 210:916–918.

    Google Scholar 

  45. Oppenheim, R. W. 1986. The absence of significant postnatal motoneuron death in the brachial and lumbar spinal cord of the rat. J. Comp. Neurol. 246:281–286.

    Google Scholar 

  46. Barde, Y. A. 1988. What, if anything, is a neurotrophic factor. Trends. Neurosci. 11:343–346.

    Google Scholar 

  47. Sendtner, M., Kreutzberg, G. W., and Thoenen, H. 1990. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 345:440–441.

    Google Scholar 

  48. Blottner, D., Druggemann, W., and Unsicker, K. 1989. Ciliary neurotrophic factor supports target-deprived preganglionic sympathetic factor supports target-deprived preganglionic sympathetic spinal cord neurons. Neurosci. Lett. 105:316–320.

    Google Scholar 

  49. Hughes, S. M., Lillien, L. E., Raff, M. C., Rohrer, H., and Sendtner, M. 1988. Ciliary neurotrophic factor induces type-2 astrocyte differentiation in culture. Nature 335:70–73.

    Google Scholar 

  50. Anderson, D. J. 1989. New roles for PDGF and CNTF in controlling the timing of glial cell differentiation in the optic nerve. Trends. Neurosci. 12:83–85.

    Google Scholar 

  51. Saadat, S., Sendtner, M., and Rohrer, H. 1989. Ciliary Neurotrophic Factor induces cholinergic differentiation of rat sympathetic neurons in culture. J. Cell Biol. 108:1807–1816.

    Google Scholar 

  52. Ernsberger, U., Sendtner, M., and Rohrer, H. 1989. Proliferation and differentiation of embryonic chick sympathetic neurons: effects of Ciliary Neuronotrophic Factor. Neuron 2:1275–1284.

    Google Scholar 

  53. Landmesser, L., and Pilar, G. 1974. Synapse formation during embryogenesis on ganglion cells lacking a periphery. J. Physiol. 241:715–736.

    Google Scholar 

  54. Narayan, C. H., and Narayan, Y. 1978. Neuronal adjustments in developing nuclear centres following transplantation of an additional optic primordium. J. Embryol. Exp. Morph. 44:53–70.

    Google Scholar 

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Special issue dedicated to Dr. Lawrence Austin

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Smet, P.J., Abrahamson, I.K., Ressom, R.E. et al. A ciliary neuronotrophic factor from peripheral nerve and smooth muscle which is not retrogradely transported. Neurochem Res 16, 613–620 (1991). https://doi.org/10.1007/BF00965546

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