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Gene Review

CNTF  -  ciliary neurotrophic factor

Gallus gallus

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Disease relevance of CNTF

  • Analysis of the specificity of action of GPA showed that, in addition to E8 ciliary ganglion neurons, the factor was able to support short-term survival of E8 dorsal root ganglion and E12 sympathetic neurons [1].
  • We can prevent apoptosis, due either to NGF or CNTF withdrawal and in either type of neuron, by overexpression of a mutant inactive ICE and an ICE inhibitor, the product of cowpox virus gene crmA [2].
  • C6 mRNA was size-fractionated, and fractions encoding CNTF-like activity were cloned into a lambda phage vector at a site distal to a T7 promoter [3].
  • Rat C6 glioma cells, which had been previously shown to have CNTF-like activity (Westermann et al., 1988), were used as source material [3].
  • Different aspects of gliosis in retinal Muller glia can be induced by CNTF, insulin, and FGF2 in the absence of damage [4].

High impact information on CNTF


Chemical compound and disease context of CNTF


Biological context of CNTF

  • Ciliary neutrophic factor (CNTF) can enhance motoneuron survival during naturally occurring cell death in the chick (Oppenheim et al, 1991) [10].
  • Complete depletion of NGF or CNTF from culture medium induces apoptosis in both types of neurons [2].
  • Immunoprecipitation experiments with rat footpad extracts provided evidence for the presence of ChAT-inducing factors other than CNTF, which may independently or together with CNTF be involved in the determination of sympathetic neuron phenotype [11].
  • The down-regulation of alpha-bungarotoxin binding sites on neurons caused by CNTF occurs with a half-time of about 19 hr and is largely reversed within a 4 d period following CNTF removal [12].
  • We show here that a factor indistinguishable from CNTF specifically down-regulates alpha-bungarotoxin binding sites on the neurons while increasing cell growth and the number of ACh receptors on the cells [12].

Anatomical context of CNTF

  • Conditioned medium produced by cultured retinal cells (most likely glial cells) exhibited opsin stimulating activity identical to that of CNTF [13].
  • CNTF has no effect on the number of ACh receptors found on chick myotubes in culture [12].
  • Immunohistochemical analysis of P21 rat footpads demonstrated CNTF-like immunoreactivity in Schwann cells but not in sweat glands, the target tissue of cholinergic sympathetic neurons [11].
  • Our results suggest that CNTF acted as an inductive signal for uncommitted progenitor cells or during early stages of rod photoreceptor differentiation, whereas other extrinsic stimulatory activities seemed to be required for further maturation [13].
  • Either NGF or CNTF also elicited neurite outgrowth from rat chromaffin cells, which amounted to approximately 15-20% at D1 and D8 and subsequently decreased to about 5-8% at D30 and virtually zero at D100 [14].

Associations of CNTF with chemical compounds

  • When addition was delayed for 3 d, CNTF failed to elicit increases either in the number of cholinergic neurons or in GABA uptake [15].
  • Here we show that CNTF induced the rapid tyrosine phosphorylation and nuclear accumulation of this protein and identify it as an avian form of the transcription factor, STAT3 [7].
  • The distribution of chick CNTF was altered neither by brefeldin A nor by chloroquine treatment [16].
  • The active species in RCM has a molecular weight (20,900 +/- 1,000) identical to that of CNTF, as determined by preparative sodium dodecyl sulfate gel electrophoresis [17].
  • These results indicate that neurons and myocytes expressing CNTF receptors are responsive to retinoic acid and suggest that retinoids may regulate cell sensitivity to cytokines during development [9].

Regulatory relationships of CNTF


Other interactions of CNTF

  • In addition, we identify a second, 100-kDa form of STAT3 that appears in response to CNTF [7].
  • The number of cells acquiring opsin immunoreactivity, determined after 3 days in vitro, was increased up to 4-fold in the presence of CNTF to maximally 10.5% of all cells [13].
  • The EC50 of the CNTF effect (2.6 pM) was virtually identical to that measured for other CNTF receptor mediated cellular responses [13].
  • We show here that a CNTF-like, VIP-inducing activity is present in rat footpads and that its increases 6-fold during the period of cholinergic sympathetic differentiation [11].
  • Ciliary neurotrophic factor (CNTF) is a neuropoietic cytokine that was identified, purified, and cloned based on its neurotrophic activity on cultured chick ciliary ganglion neurons [7].

Analytical, diagnostic and therapeutic context of CNTF

  • Ciliary neuronotrophic factor (CNTF) has been shown to enhance the survival of ciliary ganglion neurons in cell culture and has been postulated to act as a target-derived trophic factor for the neurons in vivo [12].
  • Ciliary neurotrophic factor (CNTF) has been purified 35,000-fold to homogeneity from rabbit sciatic nerves using its ability to promote the survival of chick embryo ciliary ganglion neurons as the bioassay [20].
  • Although the punctate pattern of chick CNTF immunoreactivity was not due to reuptake, chick CNTF could be found in a cellular compartment labeled after a brief incubation with dextran microbeads [16].
  • When this ciliary neuronotrophic factor (CNTF) was concentrated using ultrafiltration and subjected to Sephadex G100 and G200 chromatography, activity was detected in most of the eluted fractions [21].
  • These results show that although CNTF has no effect on naturally occurring death of chick or mouse sensory neurons, this agent has significant ability to rescue sensory neurons following axotomy [22].


  1. Purification and characterization of a trophic factor for embryonic peripheral neurons: comparison with fibroblast growth factors. Eckenstein, F.P., Esch, F., Holbert, T., Blacher, R.W., Nishi, R. Neuron (1990) [Pubmed]
  2. Prevention of apoptosis in CNTF-dependent neurons by a mutant ICE and by viral protein CrmA but not by proto-oncogene product Bcl-2. Li, W., Fishman, M.C., Yuan, J. Cell Death Differ. (1996) [Pubmed]
  3. Expression cloning of neurotrophic factors using Xenopus oocytes. Lam, A., Kloss, J., Fuller, F., Cordell, B., Ponte, P.A. J. Neurosci. Res. (1992) [Pubmed]
  4. Different aspects of gliosis in retinal Muller glia can be induced by CNTF, insulin, and FGF2 in the absence of damage. Fischer, A.J., Omar, G., Eubanks, J., McGuire, C.R., Dierks, B.D., Reh, T.A. Mol. Vis. (2004) [Pubmed]
  5. Cloning, expression during development, and evidence for release of a trophic factor for ciliary ganglion neurons. Leung, D.W., Parent, A.S., Cachianes, G., Esch, F., Coulombe, J.N., Nikolics, K., Eckenstein, F.P., Nishi, R. Neuron (1992) [Pubmed]
  6. Proliferation and differentiation of embryonic chick sympathetic neurons: effects of ciliary neurotrophic factor. Ernsberger, U., Sendtner, M., Rohrer, H. Neuron (1989) [Pubmed]
  7. Ciliary neurotrophic factor stimulates the phosphorylation of two forms of STAT3 in chick ciliary ganglion neurons. Wishingrad, M.A., Koshlukova, S., Halvorsen, S.W. J. Biol. Chem. (1997) [Pubmed]
  8. Parameters of neuritic growth from ciliary ganglion neurons in vitro: influence of laminin, schwannoma polyornithine-binding neurite promoting factor and ciliary neuronotrophic factor. Davis, G.E., Manthorpe, M., Varon, S. Brain Res. (1985) [Pubmed]
  9. Retinoic acid up-regulates ciliary neurotrophic factor receptors in cultured chick neurons and cardiomyocytes. Wang, X., Halvorsen, S.W. Neurosci. Lett. (1998) [Pubmed]
  10. Ciliary neurotrophic factor maintains motoneurons and their target muscles in developing rats. Forger, N.G., Roberts, S.L., Wong, V., Breedlove, S.M. J. Neurosci. (1993) [Pubmed]
  11. Cholinergic neuronal differentiation factors: evidence for the presence of both CNTF-like and non-CNTF-like factors in developing rat footpad. Rohrer, H. Development (1992) [Pubmed]
  12. Specific down-regulation of the alpha-bungarotoxin binding component on chick autonomic neurons by ciliary neuronotrophic factor. Halvorsen, S.W., Berg, D.K. J. Neurosci. (1989) [Pubmed]
  13. Ciliary neurotrophic factor promotes chick photoreceptor development in vitro. Fuhrmann, S., Kirsch, M., Hofmann, H.D. Development (1995) [Pubmed]
  14. Developmental changes in the responses of rat chromaffin cells to neuronotrophic and neurite-promoting factors. Unsicker, K., Skaper, S.D., Varon, S. Dev. Biol. (1985) [Pubmed]
  15. Ciliary neurotrophic factor enhances neuronal survival in embryonic rat hippocampal cultures. Ip, N.Y., Li, Y.P., van de Stadt, I., Panayotatos, N., Alderson, R.F., Lindsay, R.M. J. Neurosci. (1991) [Pubmed]
  16. Chick ciliary neurotrophic factor is secreted via a nonclassical pathway. Reiness, C.G., Seppa, M.J., Dion, D.M., Sweeney, S., Foster, D.N., Nishi, R. Mol. Cell. Neurosci. (2001) [Pubmed]
  17. Ciliary neuronotrophic factor stimulates choline acetyltransferase activity in cultured chicken retina neurons. Hofmann, H.D. J. Neurochem. (1988) [Pubmed]
  18. Onset of CNTFRalpha expression and signal transduction during neurogenesis in chick sensory dorsal root ganglia. Holst, A., Heller, S., Junghans, D., Geissen, M., Ernsberger, U., Rohrer, H. Dev. Biol. (1997) [Pubmed]
  19. Green cone opsin and rhodopsin regulation by CNTF and staurosporine in cultured chick photoreceptors. Xie, H.Q., Adler, R. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  20. Isolation and characterization of ciliary neurotrophic factor from rabbit sciatic nerves. Lin, L.F., Armes, L.G., Sommer, A., Smith, D.J., Collins, F. J. Biol. Chem. (1990) [Pubmed]
  21. Cholinergic neuronotrophic factors: fractionation properties of an extract from selected chick embryonic eye tissues. Manthorpe, M., Skaper, S., Adler, R., Landa, K., Varon, S. J. Neurochem. (1980) [Pubmed]
  22. Ciliary neurotrophic factor promotes the survival of spinal sensory neurons following axotomy but not during the period of programmed cell death. Lo, A.C., Li, L., Oppenheim, R.W., Prevette, D., Houenou, L.J. Exp. Neurol. (1995) [Pubmed]
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