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Gene Review

NTF3  -  neurotrophin 3

Gallus gallus

Synonyms: HDNF, NGF-2, NGF2, NT-3, NT3
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Disease relevance of NTF3


High impact information on NTF3

  • These data implicate a role for the p75 receptor in NGF's neurotoxicity and indicate that this receptor is involved in the mechanism by which ION neurons respond to BDNF and NT-3 in the target [5].
  • KI receptors, like full-length receptors, were tyrosine phosphorylated in response to NT-3 and mediated the transformation of chick embryo fibroblasts and process outgrowth from rat PC12 cells [6].
  • These results indicate that alternative splicing of trkC transcripts is an important mechanism for regulating cellular responses to NT-3 [6].
  • Thus, specific high-affinity NT-3 receptors exist on sensory neurons that can readily discriminate between three structurally related ligands [7].
  • Inhibition of the NT-3 receptor TrkC, early in chick embryogenesis, results in severe reductions in multiple neuronal subpopulations in the dorsal root ganglia [8].

Biological context of NTF3

  • Thus, NT-3 promotes the conversion of neuroepithelial cells into neurons, whereas BDNF and NGF control the programmed cell death (apoptosis) that affects early postmitotic neuroblasts [9].
  • Treatment with NT-3 showed down-regulation of trkB levels at all developmental stages [10].
  • We found that high concentrations of BDNF and NT-3 administered together, and low concentrations of both neurotrophins combined and administered with RA suppress otocyst cell numbers after 24 h in vitro [11].
  • Here we show that only a single conservative amino acid substitution distinguishes the chicken mature NT-3 protein from its mammalian counterpart [12].
  • We also note the presence of amino acid sequence motifs in the precursor protein sequences of chicken BDNF and NT-3 that are universally conserved among all known mammalian neurotrophin precursors and have been demonstrated to play a crucial role in promoting correct processing of the pro-proteins [12].

Anatomical context of NTF3

  • BDNF and NT-3 regulation of trkB and trkC mRNA levels in the developing chick spinal cord [10].
  • Presynaptic neurotrophin-3 increases the number of tectal synapses, vesicle density, and number of docked vesicles in chick embryos [13].
  • To determine whether presynaptically derived neurotrophins may contribute to synaptic plasticity, we examined whether neurotrophin-3 (NT-3) changed the number, size, vesicle content, or vesicle distribution of synapses within the retinorecipient layers of the chick optic tectum [13].
  • In this system, endogenous NT-3 derives presynaptically from retinal ganglion cell axons [13].
  • In contrast, NT-3 had no effect on the length of neurites [14].

Associations of NTF3 with chemical compounds


Physical interactions of NTF3

  • E7 and E14 HNT-3R could be distinguished from each other on the basis of different inhibition patterns of 125I-NT-3 binding in the presence of nerve growth factor or brain-derived neurotrophic factor [19].

Co-localisations of NTF3


Regulatory relationships of NTF3

  • TrkC mRNA levels were down-regulated at all developmental stages with NT-3 treatment and at E10 and E15 with BDNF treatment [10].
  • A similar high level of neurotrophin-3 neither promotes the survival of BDNF-dependent ventrolateral trigeminal ganglion neurons nor affects the dose response of these neurons to BDNF [21].

Other interactions of NTF3


Analytical, diagnostic and therapeutic context of NTF3

  • We used an expression system to supply developing chicks with the neurotrophic factor and then analysed the receptor mRNA levels at embryonic day 8 (E8), E10 and E15 using semi-quantitative RT-PCR [10].


  1. Development of a fast transient potassium current in chick cochlear ganglion neurons. García-Díaz, J.F. Hear. Res. (1999) [Pubmed]
  2. Functional interaction and partial homology between human immunodeficiency virus and neuroleukin. Lee, M.R., Ho, D.D., Gurney, M.E. Science (1987) [Pubmed]
  3. Herpes simplex virus type 1-mediated transfer of neurotrophin-3 stimulates survival of chicken auditory sensory neurons. Carnicero, E., Knipper, M., Tan, J., Alonso, M.T., Schimmang, T. Neurosci. Lett. (2002) [Pubmed]
  4. Characterization of growth/differentiation factor 5 (GDF-5) as a neurotrophic factor for cultured neurons from chicken dorsal root ganglia. Farkas, L.M., Scheuermann, S., Pohl, J., Unsicker, K., Krieglstein, K. Neurosci. Lett. (1997) [Pubmed]
  5. Positive and negative effects of neurotrophins on the isthmo-optic nucleus in chick embryos. von Bartheld, C.S., Kinoshita, Y., Prevette, D., Yin, Q.W., Oppenheim, R.W., Bothwell, M. Neuron (1994) [Pubmed]
  6. Isoforms of the avian TrkC receptor: a novel kinase insertion dissociates transformation and process outgrowth from survival. Garner, A.S., Large, T.H. Neuron (1994) [Pubmed]
  7. Binding of neurotrophin-3 to its neuronal receptors and interactions with nerve growth factor and brain-derived neurotrophic factor. Rodríguez-Tébar, A., Dechant, G., Götz, R., Barde, Y.A. EMBO J. (1992) [Pubmed]
  8. Inhibition of the NT-3 receptor TrkC, early in chick embryogenesis, results in severe reductions in multiple neuronal subpopulations in the dorsal root ganglia. Lefcort, F., Clary, D.O., Rusoff, A.C., Reichardt, L.F. J. Neurosci. (1996) [Pubmed]
  9. Neurotrophins and other growth factors in the generation of retinal neurons. Frade, J.M., Bovolenta, P., Rodríguez-Tébar, A. Microsc. Res. Tech. (1999) [Pubmed]
  10. BDNF and NT-3 regulation of trkB and trkC mRNA levels in the developing chick spinal cord. Gibbons, A.S., Bailey, K.A. Neurosci. Lett. (2005) [Pubmed]
  11. Neurotrophic factors modulate hair cells and their potassium currents in chick otocyst explants. Sokolowski, B.H., Csus, J., Hafez, O.I., Haggerty, H.S. Eur. J. Neurosci. (1999) [Pubmed]
  12. Gene sequences of chicken BDNF and NT-3. Maisonpierre, P.C., Belluscio, L., Conover, J.C., Yancopoulos, G.D. DNA Seq. (1992) [Pubmed]
  13. Presynaptic neurotrophin-3 increases the number of tectal synapses, vesicle density, and number of docked vesicles in chick embryos. Wang, X., Butowt, R., von Bartheld, C.S. J. Comp. Neurol. (2003) [Pubmed]
  14. Neurotrophin-3 increases neurite outgrowth and apoptosis in explants of the chicken neural plate. Li, R., Bernd, P. Dev. Neurosci. (1999) [Pubmed]
  15. Expression of neurotrophin-3 (NT-3) and anterograde axonal transport of endogenous NT-3 by retinal ganglion cells in chick embryos. von Bartheld, C.S., Butowt, R. J. Neurosci. (2000) [Pubmed]
  16. Purification of a ciliary neurotrophic factor from bovine heart. Watters, D.J., Hendry, I.A. J. Neurochem. (1987) [Pubmed]
  17. Trophic factors from chromaffin granules promote survival of peripheral and central nervous system neurons. Lachmund, A., Gehrke, D., Krieglstein, K., Unsicker, K. Neuroscience (1994) [Pubmed]
  18. Ethanol exposure affects trophic factor activity and responsiveness in chick embryo. Heaton, M.B., Swanson, D.J., Paiva, M., Walker, D.W. Alcohol (1992) [Pubmed]
  19. Neurotrophin-3 receptors in the developing chicken retina. Rodríguez-Tébar, A., de la Rosa, E.J., Arribas, A. Eur. J. Biochem. (1993) [Pubmed]
  20. The identification of neurotrophic factor as a transferrin. Beach, R.L., Popiela, H., Festoff, B.W. FEBS Lett. (1983) [Pubmed]
  21. High specificity of neurotrophins in the embryonic chicken trigeminal system. Pinon, L.G., Robinson, M., Davies, A.M. Eur. J. Neurosci. (1995) [Pubmed]
  22. Differential effects of the trophic factors BDNF, NT-4, GDNF, and IGF-I on the isthmo-optic nucleus in chick embryos. Janiga, T.A., Rind, H.B., von Bartheld, C.S. J. Neurobiol. (2000) [Pubmed]
  23. Stem cell factor is a neurotrophic factor for neural crest-derived chick sensory neurons. Carnahan, J.F., Patel, D.R., Miller, J.A. J. Neurosci. (1994) [Pubmed]
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