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Journal of Cell Science, Vol 108, Issue 11 3523-3530, Copyright © 1995 by Company of Biologists
JOURNAL ARTICLES |
EJ Williams, B Mittal, FS Walsh and P Doherty
Department of Experimental Pathology, UMDS, Guy's Hospital, London, UK.
We have cultured cerebellar neurons on monolayers of cortical astrocytes in control medium or medium containing recombinant basic fibroblast growth factor (FGF). FGF was found to inhibit neurite outgrowth, with a significant effect seen at 0.5 ng/ml and a maximal effect at 10 ng/ml. FGF increased the production of arachidonic acid (AA) in cerebellar neurons, and when added directly to cultures or generated endogenously via activation of phospholipase A2 using melittin, this second messenger could mimic the inhibitory effect of FGF. FGF and AA could also specifically inhibit neurite outgrowth stimulated by three cell adhesion molecules (NCAM, N-cadherin and L1) expressed in transfected fibroblasts, or in the case of L1 bound to a tissue culture substratum. These data demonstrate that, in certain cellular contexts, FGF can act as an inhibitory cue for axonal growth and that arachidonic acid is the second messenger responsible for this activity. We discuss the possibility that arachidonic acid inhibits neurite outgrowth by desensitising the second messenger pathway underlying neuronal responsiveness to cell adhesion molecules.
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  E.-J. Williams, F. S. Walsh, and P. Doherty The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response J. Cell Biol., February 18, 2003; 160(4): 481 - 486. [Abstract] [Full Text] [PDF]
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P. Niethammer, M. Delling, V. Sytnyk, A. Dityatev, K. Fukami, and M. Schachner Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis J. Cell Biol., April 29, 2002; 157(3): 521 - 532. [Abstract] [Full Text] [PDF]
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P. Niethammer, M. Delling, V. Sytnyk, A. Dityatev, K. Fukami, and M. Schachner Cosignaling of NCAM via lipid rafts and the FGF receptor is required for neuritogenesis J. Cell Biol., April 29, 2002; 157(3): 521 - 532. [Abstract] [Full Text] [PDF]
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