Journal of Neurocytology

, Volume 32, Issue 5–8, pp 931–941 | Cite as

Neurotrophic regulation of the development and function of the neuromuscular synapses

  • Bai Lu
  • Hyun-Soo Je


Recent studies have established that one of the major functions of neurotrophic factors is to regulate synaptic development and plasticity. This owes a great deal to the studies using the neuromuscular junction (NMJ) as a model system. In this review, we summarize the effects of various neurotrophic factors on the development and function of the neuromuscular synapses. We describe experiments addressing the role of neurotrophins, as well as that of other factors (GFLs, TGF-βs, and Wnts). The synaptic effects of neurotrophic factors are divided into two categories: acute effects on synaptic transmission and plasticity occurring within seconds or minutes after cells are exposed to a particular factor, and long-term regulation of synaptic structure and function that takes days to accomplish. We consider the presynaptic effects on the release of the neurotransmitter ACh, as well as the postsynaptic effects on the clustering of ACh receptors. Further studies of the mechanisms underlying these regulatory effects will help us better understand how neurotrophic factors can achieve diverse and synapse-specific modulation in the brain.


Neurotrophic Factor Synaptic Transmission Regulatory Effect Acute Effect Neuromuscular Junction 
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.


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  1. AAKALU, G., SMITH, W. B., NGUYEN, N., JIANG, C. & SCHUMAN, E. M. (2001) Dynamic visualization of local protein synthesis in hippocampal neurons. Neuron 30, 48–502.PubMedGoogle Scholar
  2. ABERLE, H., HAGHIGHI, A. P., FETTER, R. D., MCCABE, B. D., MAGALHAES, T. R. & GOODMAN, C. S. (2002) Wishful thinking encodes a BMP type II receptor that regulates synaptic growth in Drosophila. Neuron 33, 54–558.PubMedGoogle Scholar
  3. AIRAKSINEN, M. S., TITIEVSKY, A. & SAARMA, M. (1999a) GDNFfamily neurotrophic factor signaling: Four masters, one servant? Mol. Cell. Neurosci. 13, 31–325.PubMedGoogle Scholar
  4. AIRAKSINEN, M. S., TITIEVSKY, A. & SAARMA, M. (1999b) GDNFfamily neurotrophic factor signaling: Four masters, one servant? Mol. Cell. Neurosci. 13, 31–325.PubMedGoogle Scholar
  5. AIRAKSINEN, M. S. & SAARMA, M. (2002) The GDNF family: Signalling, biological functions and therapeutic value. Nat. Rev. Neurosci. 3, 38–394.PubMedGoogle Scholar
  6. ARCE, V., POLLOCK, R. A., PHILIPPE, J. M., PENNICA, D., HENDERSON, C. E. & DELAPEYRIERE, O. (1998) Synergistic effects of schwann-and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1). J. Neurosci. 18, 144–1448.PubMedGoogle Scholar
  7. ATTISANO, L. & WRANA, J. L. (2002) Signal transduction by the TGF-beta superfamily. Science 296, 164–1647.PubMedGoogle Scholar
  8. BALDELLI, P., MAGNELLI, V. & CARBONE, E. (1999) Selective up-regulation of P-and R-type Ca2+ channels in rat embryo motoneurons by BDNF. Eur. J. Neurosci. 11, 112–1133.PubMedGoogle Scholar
  9. BALOH, R. H., ENOMOTO, H., JOHNSON, E. M., JR. & MILBRANDT, J. (2000) The GDNF family ligands and receptors—Implications for neural development. Curr. Opin. Neurobiol. 10, 10–110.PubMedGoogle Scholar
  10. BARBACID, M. (1994) The Trk family of neurotrophin receptors. J. Neurobiol. 25, 138–1403.PubMedGoogle Scholar
  11. BELLUARDO, N., WESTERBLAD, H., MUDO, G., CASABONA, A., BRUTON, J., CANIGLIA, G., PASTORIS, O., GRASSI, F. & IBANEZ, C. F. (2001) Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4. Mol. Cell Neurosci. 18, 5–67.PubMedGoogle Scholar
  12. BILAK, M. M., SHIFRIN, D. A., CORSE, A. M., BILAK, S. R. & KUNCL, R. W. (1999) Neuroprotective utility and neurotrophic action of neurturin in postnatal motor neurons: Comparison with GDNF and persephin. Mol. Cell Neurosci. 13, 32–336.PubMedGoogle Scholar
  13. BOTHWELL, M. (1995) Functional interactions of neurotrophins and neurotrophin receptors. Annu. Rev. Neurosci. 18, 22–253.PubMedGoogle Scholar
  14. BOULANGER, L. & POO, M. M. (1999a) Presynaptic depolarization facilitates neurotrophin-induced synaptic potentiation. Nat. Neurosci. 2, 34–351.PubMedGoogle Scholar
  15. BOULANGER, L. & POO, M. M. (1999b) Gating of BDNFinduced synaptic potentiation by cAMP. Science 284, 198–1984.PubMedGoogle Scholar
  16. CHANG, S. & POPOV, S. V. (1999) Long-range signaling within growing neurites mediated by neurotrophin-3. Proc. Natl. Acad. Sci. USA 96, 409–4100.PubMedGoogle Scholar
  17. CHAO, M. V. (1994) The p75 neurotrophin receptor. J. Neurobiol. 25, 137–1385.PubMedGoogle Scholar
  18. CHAO, M. V. & BOTHWELL, M. (2002) Neurotrophins: To cleave or not to cleave. Neuron 33,–12.PubMedGoogle Scholar
  19. CHITNIS, A. B. (1999) Control of neurogenesis—Lessons from frogs, fish and flies. Curr. Opin. Neurobiol. 9, 1–25.PubMedGoogle Scholar
  20. FU, A. K., IP, F. C., LAI, K. O., TSIM, K. W. & IP, N. Y. (1997) Muscle-derived neurotrophin-3 increases the aggregation of acetylcholine receptors in neuron-muscle cocultures. Neuroreport 8, 389–3900.PubMedGoogle Scholar
  21. FUNAKOSHI, H., BELLUARDO, N., ARENAS, E., YAMAMOTO, Y., CASABONA, A., PERSSON, H. & IBANEZ, C. F. (1995) Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. Science 268, 149–1499.PubMedGoogle Scholar
  22. GAGE, F. H., BATCHELOR, P., CHEN, K. S., CHIN, D., HIGGINS, G. A., KOH, S., DEPUTY, S., ROSENBERG, M. B., FISCHER, W. & BJORKLUND, A. (1989) NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum. Neuron 2, 117–1184.PubMedGoogle Scholar
  23. GARCES, A., HAASE, G., AIRAKSINEN, M. S., LIVET, J., FILIPPI, P. & DELAPEYRIERE, O. (2000) GFRalpha 1 is required for development of distinct subpopulations of motoneuron. J. Neurosci. 20, 499–5000.PubMedGoogle Scholar
  24. GOLDEN, J. P., DEMARO, J. A., OSBORNE, P. A., MILBRANDT, J. & JOHNSON, E. M., JR. (1999) Expression of neurturin,GDNF, andGDNFfamily-receptor mRNAin the developing and mature mouse. Exp. Neurol. 158, 50–528.PubMedGoogle Scholar
  25. GOMEZ-PINILLA, F., YING, Z., OPAZO, P., ROY, R. R. & EDGERTON, V. R. (2001) Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur. J. Neurosci. 13, 107–1084.PubMedGoogle Scholar
  26. GOMEZ-PINILLA, F., YING, Z., ROY, R. R., MOLTENI, R. & EDGERTON, V. R. (2002) Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J. Neurophysiol. 88, 218–2195.PubMedGoogle Scholar
  27. GONZALEZ, M., RUGGIERO, F. P., CHANG, Q., SHI, Y. J., RICH, M. M., KRANER, S. & BALICEGORDON, R. J. (1999) Disruption of Trkb-mediated signaling induces disassembly of postsynaptic receptor clusters at neuromuscular junctions. Neuron 24, 56–583.PubMedGoogle Scholar
  28. HALL, A. C., LUCAS, F. R. & SALINAS, P. C. (2000) Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell 100, 52–535.PubMedGoogle Scholar
  29. HE, X., YANG, F., XIE, Z. & LU, B. (2000) Intracellular Ca2+ and Ca2+/Calmodulin-dependent kinase II mediate acute potentiation of neurotransmitter release by neurotrophin-3. J. Cell Biol. 149, 78–792.PubMedGoogle Scholar
  30. HENDERSON, C. E., CAMU, W., METTLING, C., GOUIN, A., POULSEN, K., KARIHALOO, M., RULLAMAS, J., EVANS, T., MCMAHON, S. B., ARMANINI, M. P., BERKEMEIER, L., PHILLIPS, H. S. & ROSENTHAL, A. (1993) Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature 363, 26–270.Google Scholar
  31. HENDERSON, C. E., PHILLIPS, H. S., POLLOCK, R. A., DAVIES, A. M., LEMEULLE, C., ARMANINI, M., SIMMONS, L., MOFFET, B., VANDLEN, R. A., SIMPSON, L. C., KOLIATSOS, V. E. & ROSENTHAL, A. (1994) GDNF: A potent survival factor for motoneurons present in peripheral nerve and muscle. Science 266, 106–1064.PubMedGoogle Scholar
  32. HO, T. W., BRISTOL, L. A., COCCIA, C., LI, Y., MILBRANDT, J., JOHNSON, E., JIN, L., BAR-PELED, O., GRIFFIN, J. W. & ROTHSTEIN, J. D. (2000) TGFbeta trophic factors differentially modulate motor axon outgrowth and protection from excitotoxicity. Exp. Neurol. 161, 66–675.PubMedGoogle Scholar
  33. HUANG, E. J. & REICHARDT, L. F. (2001) Neurotrophins: Roles in neuronal development and function. Ann. Rev. Neurosci. 24, 67–736.PubMedGoogle Scholar
  34. HUELSKEN, J. & BIRCHMEIER, W. (2001) New aspects of Wnt signaling pathways in higher vertebrates. Current Opinion in Genetics & Development 11, 54–553.Google Scholar
  35. KAPLAN, D. R. & MILLER, F. D. (2000) Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 10, 38–391.PubMedGoogle Scholar
  36. KELLER-PECK, C. R., FENG, G., SANES, J. R., YAN, Q., LICHTMAN, J. W. & SNIDER, W. D. (2001) Glial cell line-derived neurotrophic factor administration in postnatal life results in motor unit enlargement and continuous synaptic remodeling at the neuromuscular junction. J. Neurosci. 21, 613–6146.PubMedGoogle Scholar
  37. KLEIMAN, R. J., TIAN, N., KRIZAJ, D., HWANG, T. N., COPENHAGEN, D. R. & REICHARDT, L. F. (2000) BDNF-Induced potentiation of spontaneous twitching in innervated myocytes requires calcium release fromintracellular stores. J. Neurophysiol. 84, 47–483.PubMedGoogle Scholar
  38. KOLIATSOS, V. E., CLATTERBUCK, R. E., WINSLOW, J. W., CAYOUETTE, M. H. & PRICE, D. L. (1993) Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 10, 35–367.PubMedGoogle Scholar
  39. KRIEGLSTEIN, K., HENHEIK, P., FARKAS, L., JASZAI, J., GALTER, D., KROHN, K. & UNSICKER, K. (1998) Glial cell line-derived neurotrophic factor requires transforming growth factor-beta for exerting its full neurotrophic potential on peripheral and CNS neurons. J. Neurosci. 18, 982–9834.PubMedGoogle Scholar
  40. KRYLOVA, O., HERREROS, J., CLEVERLEY, K. E., EHLER, E., HENRIQUEZ, J. P., HUGHES, S. M. & SALINAS, P. C. (2002) WNT-3, expressed by motoneurons, regulates terminal arborization of neurotrophin-3-responsive spinal sensory neurons. Neuron 35, 104–1056.PubMedGoogle Scholar
  41. LEE, R., KERMANI, P., TENG, K. K. & HEMPSTEAD, B. L. (2002) Regulation of cell survival by secreted proneurotrophins. Science 294, 194–1948.Google Scholar
  42. LEITNER, M. L., MOLLIVER, D. C., OSBORNE, P. A., VEJSADA, R., GOLDEN, J. P., LAMPE, P. A., KATO, A. C., MILBRANDT, J. & JOHNSON, E. M., JR. (1999) Analysis of the retrograde transport of glial cell line-derived neurotrophic factor (GDNF), neurturin, and persephin suggests that in vivo signaling for the GDNF family is GFRalpha coreceptor-specific. J. Neurosci. 19, 932–9331.PubMedGoogle Scholar
  43. LEWIN, G. R. & BARDE, Y.-A. (1996) Physiology of the neurotrophins. Annu. Rev. Neurosci. 19, 28–317.PubMedGoogle Scholar
  44. LI, H. S., XU, X. Z. & MONTELL, C. (1999) Activation of a TRPC3-dependent cation current through the neurotrophin BDNF. Neuron 24, 26–273.PubMedGoogle Scholar
  45. LIN, L. F., DOHERTY, D. H., LILE, J. D., BEKTESH, S. & COLLINS, F. (1993) GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260, 113–1132.PubMedGoogle Scholar
  46. LINDEN, D. J. (1996) A protein synthesis-dependent late phase of cerebellar long-term depression. Neuron 17, 48–490.PubMedGoogle Scholar
  47. LIOU, J. C. & FU, W. M. (1997) Regulation of quantal secretion from developing motoneurons by postsynaptic activity-dependent release of NT-3. J. Neurosci. 17, 245–2468.PubMedGoogle Scholar
  48. LIOU, J. C., YANG, R. S. & FU, W. M. (1997) Regulation of quantal secretion by neurotrophic factors at developing motoneurons in Xenopus cell cultures. J. Physiol. (Lond.) 503, 12–139.Google Scholar
  49. LOEB, J. A. & FISCHBACH, G. D. (1997) Neurotrophic factors increase neuregulin expression in embryonic ventral spinal cord neurons. J. Neurosci. 17, 141–1424.PubMedGoogle Scholar
  50. LOEB, J. A., HMADCHA, A., FISCHBACH, G. D., LAND, S. J. & ZAKARIAN, V. L. (2002) Neuregulin expression at neuromuscular synapses is modulated by synaptic activity and neurotrophic factors. J. Neurosci. 22, 220–2214.PubMedGoogle Scholar
  51. LOHOF, A. M., IP, N. Y. & POO, M. M. (1993) Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363, 35–353.PubMedGoogle Scholar
  52. LU, B. & FIGUROV, A. (1997) Role of neurotrophins in synapse development and plasticity. Rev. Neurosci. 8, –12.PubMedGoogle Scholar
  53. MARQUES, G., BAO, H., HAERRY, T. E., SHIMELL, M. J., DUCHEK, P., ZHANG, B. & O'CONNOR, M. B. (2002) The Drosophila BMP type II receptor Wishful Thinking regulates neuromuscular synapse morphology and function. Neuron 33, 52–543.PubMedGoogle Scholar
  54. MASSAGUE, J. (1998) TGF-beta signal transduction. Annu. Rev. Biochem. 67, 75–791.PubMedGoogle Scholar
  55. MASSAGUE, J. (2000) How cells read TGF-beta signals. Nat. Rev. Mol. Cell Biol. 1, 16–178.PubMedGoogle Scholar
  56. MCLENNAN, I. S. & KOISHI, K. (1994) Transforming growth factor-beta-2 (TGF-beta 2) is associated with mature rat neuromuscular junctions. Neuroscience Letters 177, 15–154.PubMedGoogle Scholar
  57. MIKAELS, A., LIVET, J., WESTPHAL, H., DE LAPEYRIERE, O. & ERNFORS, P. (2000) A dynamic regulation of GDNF-family receptors correlates with a specific trophic dependency of cranial motor neuron subpopulations during development. Eur. J. Neurosci. 12, 44–456.PubMedGoogle Scholar
  58. MILBRANDT, J., DE SAUVAGE, F. J., FAHRNER, T. J., BALOH, R. H., LEITNER, M. L., TANSEY, M. G., LAMPE, P. A., HEUCKEROTH, R. O., KOTZBAUER, P. T., SIMBURGER, K. S., GOLDEN, J. P., DAVIES, J. A., VEJSADA, R., KATO, A. C., HYNES, M., SHERMAN, D., NISHIMURA, M., WANG, L. C., VANDLEN, R., MOFFAT, B., KLEIN, R. D., POULSEN, K., GRAY, C., GARCES, A., JOHNSON, E. M., JR. et al. (1998) Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 20, 24–253.PubMedGoogle Scholar
  59. MING, G. L., WONG, S. T., HENLEY, J., YUAN, X. B., SONG, H. J., SPITZER, N. C. & POO, M. M. (2002) Adaptation in the chemotactic guidance of nerve growth cones. Nature 417, 41–418.PubMedGoogle Scholar
  60. MOORE, M. W., KLEIN, R. D., FARINAS, I., SAUER, H., ARMANINI, M., PHILLIPS, H., REICHARDT, L. F., RYAN, A. M., CARVER, M. K. & ROSENTHAL, A. (1996) Renal and neuronal abnormalities in mice lacking GDNF. Nature 382, 7–79.PubMedGoogle Scholar
  61. NGUYEN, Q. T., PARSADANIAN, A. S., SNIDER, W. D. & LICHTMAN, J. W. (1998) Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle. Science 279, 172–1729.PubMedGoogle Scholar
  62. NICK, T. A. & RIBERA, A. B. (2000) Synaptic activity modulates presynaptic excitability. Nat. Neurosci. 3, 14– 149.PubMedGoogle Scholar
  63. OLAFSSON, P., SOARES, H. D., WANG, T., HERZOG, K.-H., MORGAN, J. I. & LU, B. (1997) The Ca2+ binding protein frequenin is a nervous system-specific protein preferentially localized in neurites. Mol. Brain Res. 44, 7–82.PubMedGoogle Scholar
  64. OPPENHEIM, R. W., YIN, Q.-W., PREVETTE, D. & YAN, Q. (1992) Brain-derived neurotrophic factor rescues developing avian motorneurons fromcell death. Nature 360, 75–757.PubMedGoogle Scholar
  65. OPPENHEIM, R. W., HOUENOU, L. J., JOHNSON, J. E., LIN, L. F., LI, L., LO, A. C., NEWSOME, A. L., PREVETTE, D. M. & WANG, S. (1995) Developing motor neurons rescued from programmed and axotomyinduced cell death by GDNF. Nature 373, 34–346.PubMedGoogle Scholar
  66. OPPENHEIM, R. W., HOUENOU, L. J., PARSADANIAN, A. S., PREVETTE, D., SNIDER, W. D. & SHEN, L. (2000) Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: Regulation of programmed cell death among motoneuron subtypes. J. Neurosci. 20, 500–5011.PubMedGoogle Scholar
  67. PACKARD, M., KOO, E. S., GORCZYCA, M., SHARPE, J., CUMBERLEDGE, S. & BUDNIK, V. (2002) The Drosophila Wnt, wingless, provides an essential signal for pre-and postsynaptic differentiation. Cell 111, 31–330.PubMedGoogle Scholar
  68. SANCHEZ, M. P., SILOS, S. I., FRISEN, J., HE, B., LIRA, S. A. & BARBACID, M. (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382, 7–73.PubMedGoogle Scholar
  69. SANES, J. R. & LICHTMAN, J. W. (1999) Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22, 38–442.PubMedGoogle Scholar
  70. SENDTNER, M., HOLTMANN, B., KOLBECK, R., THOENEN, H. & BARDE, Y.-A. (1992) Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 360, 75–759.PubMedGoogle Scholar
  71. SONG, H., MING, G., HE, Z., LEHMANN, M., TESSIERLAVIGNE, M. & POO, M. (1998) Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281, 151–1518.PubMedGoogle Scholar
  72. SONG, H. J. & POO, M. M. (1999) Signal transduction underlying growth cone guidance by diffusible factors. Curr. Opin. Neurobiol. 9, 35–363.PubMedGoogle Scholar
  73. STOOP, R. & POO, M. M. (1995) Potentiation of transmitter release by ciliary neurotrophic factor requires somatic signaling. Science 267, 69–699.PubMedGoogle Scholar
  74. STOOP, R. & POO, M. M. (1996) Synaptic modulation by neurotrophic factors: Differential and synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor. J. Neurosci. 16, 325–3264.PubMedGoogle Scholar
  75. SWEENEY, S. T. & DAVIS, G. W. (2002) Unrestricted synaptic growth in spinster—A late endosomal protein implicated in TGF-[Beta;]-mediated synaptic growth regulation. Neuron 36, 40–416.PubMedGoogle Scholar
  76. TAKEI, N., KAWAMURA, M., HARA, K., YONEZAWA, K. & NAWA, H. (2001) Brain-derived neurotrophic factor enhances neuronal translation by activating multiple initiation processes: Comparison with the effects of insulin. J. Biol. Chem. 276, 4281–42825.PubMedGoogle Scholar
  77. TREANOR, J. J., GOODMAN, L., DE, S. F., STONE, D. M., POULSEN, K. T., BECK, C. D., GRAY, C., ARMANINI, M. P., POLLOCK, R. A., HEFTI, F., PHILLIPS, H. S., GODDARD, A., MOORE, M. W., BUJ, B. A., DAVIES, A. M., ASAI, N., TAKAHASHI, M., VANDLEN, R., HENDERSON, C. E. & ROSENTHAL, A. (1996) Characterization of a multicomponent receptor for GDNF. Nature 382, 8–83.PubMedGoogle Scholar
  78. WANG, C., YANG, F., HE, X., CHOW, A., DU, J., RUSSELL, J. & LU, B. (2001) Ca2+-binding protein frequenin mediates GDNF-induced synaptic facilitation by potentiating Ca2+ channels. Neuron 32, 9–112.Google Scholar
  79. WANG, C. Y., YANG, F., HE, X. P., JE, H. S., ZHOU, J. Z., ECKERMANN, K., KAWAMURA, D., FENG, L., SHEN, L. & LU, B. (2002) Regulation of neuromuscular synapse development by glial cell line-derived neurotrophic factor and neurturin. J. Biol. Chem. 277, 1061–10625.PubMedGoogle Scholar
  80. WANG, T., XIE, K. W. & LU, B. (1995) Neurotrophins promote maturation of developing neuromuscular synapses. J. Neurosci. 15, 479–4805.PubMedGoogle Scholar
  81. WANG, X. H. & POO, M. M. (1997) Potentiation of developing synapses by postsynaptic release of neurotrophin-4. Neuron 19, 82–835.PubMedGoogle Scholar
  82. WELLS, D. G., MCKECHNIE, B. A., KELKAR, S. & FALLON, J. R. (1999) Neurotrophins regulate agrininduced postsynaptic differentiation. Proc. Natl. Acad. Sci. USA 96, 111–1117.PubMedGoogle Scholar
  83. WIDENFALK, J., NOSRAT, C., TOMAC, A., WESTPHAL, H., HOFFER, B. & OLSON, L. (1997) Neurturin and glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta), novel proteins related to GDNF and GDNFR-alpha with specific cellular patterns of expression suggesting roles in the developing and adult nervous system and in peripheral organs. J. Neurosci. 17, 850–8519.PubMedGoogle Scholar
  84. WONG, V., ARRIAGA, R., IP, N. Y. & LINDSAY, R. M. (1993) The neurotrophins BDNF, NT-3 and NT-4/5, but not NGF, upregulate the cholinergic phenotype of developing motor neurons. Eur. J. Neurosci. 5, 46–474.PubMedGoogle Scholar
  85. XIE, K., WANG, T., OLAFSSON, P., MIZUNO, K. & LU, B. (1997) Activity-dependent expression of NT-3 in muscle cells in culture: Implication in the development of neuromuscular junctions. J. Neurosci. 17, 294–2958.PubMedGoogle Scholar
  86. YAN, Q., ELLIOTT, J. & SNIDER, W. D. (1992) Brainderived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 360, 75–755.PubMedGoogle Scholar
  87. YAN, Q., ELLIOTT, J. L., MATHESON, C., SUN, J., ZHANG, L., MU, X., REX, K. L. & SNIDER, W. D. (1993) Influences of neurotrophins on mammalian motoneurons in vivo. J. Neurobiol. 24, 155–1577.PubMedGoogle Scholar
  88. YAN, Q., MATHESON, C. & LOPEZ, O. T. (1995) In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature 373, 34–344.PubMedGoogle Scholar
  89. YANG, F., HE, X., FENG, L., MIZUNO, K., LIU, X., RUSSELL, J., XIONG, W. & LU, B. (2001) PI3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. Nature Neurosci. 4, 1–28.PubMedGoogle Scholar
  90. ZHANG, X. & POO, M. M. (2002) Localized synaptic potentiation by BDNF requires local protein synthesis in the developing axon. Neuron 36, 67–688.PubMedGoogle Scholar
  91. ZWICK, M., TENG, L., MU, X., SPRINGER, J. E. & DAVIS, B. M. (2001) Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation. Exp. Neurol. 171, 34– 350.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Bai Lu
    • 1
  • Hyun-Soo Je
    • 1
  1. 1.Section on Neural Development & Plasticity, NICHD, NIHBethesdaUSA

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