FGF inhibits neurite outgrowth over monolayers of astrocytes and fibroblasts expressing transfected cell adhesion molecules.
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.
Williams
E J
EJ
Department of Experimental Pathology, UMDS, Guy's Hospital, London, UK.
Mittal
B
B
Walsh
F S
FS
Doherty
P
P
D016475:3T3 Cells / Q000166:cytology; D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis; D001253:Astrocytes / Q000166:cytology; D015820:Cadherins / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000166:cytology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014162:Transfection / Q000502:physiology; D014316:Tritium / Q000378:metabolism
D015820:Cadherins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D016718:Arachidonic Acid; D011189:Potassium Chloride