Characterization of basic fibroblast growth factor-mediated acceleration of axonal branching in cultured rat hippocampal neurons.
We analyzed in more detail the effect of basic fibroblast growth factor (bFGF) on morphogenesis of rat hippocampal neurons in dissociated cell culture. As a result, we found that bFGF selectively promoted the bifurcation and growth of axonal branches without affecting the elongation rate of primary axons. The dendritic outgrowth was rather inhibited by bFGF. These effects of bFGF resulted in increased complexity of axonal trees. The effect of bFGF was concentration dependent (0.1-10 ng/ml) and was abolished by the presence of anti-bFGF neutralizing antibody. The accelerated axonal branch formation in the presence of bFGF was restored to the basal rate following removal of bFGF, suggesting that the action of bFGF is reversible and that the continuous presence is required for bFGF to accelerate the branch formation. bFGF probably works as a progression signal rather than as a triggering signal. The bFGF-mediated acceleration of axonal branch formation was blocked by treatment with heparitinase and by tyrosine inhibitors, herbimycin A and lavendustin A, indicating the importance of heparan sulfate and tyrosine kinase in bFGF signal transduction. Treatment with a protein kinase C activator phorbol-12-myristate-13-acetate did not significantly affect the neurite branching, and the action of bFGF was not blocked by a protein kinase C inhibitor staurosporine. Protein kinase C is unlikely to play a role in branch formation. The novel action of bFGF as a regulator of axonal branching must be a particularly useful model for the study of neuritogenesis and synaptogenesis of brain neurons.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
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Aoyagi
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Nishikawa
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Saito
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Abe
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001369:Axons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D016227:Benzoquinones; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D016222:Fibroblast Growth Factor 2 / Q000276:immunology / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D047029:Lactams, Macrocyclic; D016501:Neurites / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010636:Phenols / Q000494:pharmacology; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D000470:Alkaloids; D000906:Antibodies; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D010636:Phenols; D011809:Quinones; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D017828:Rifabutin; C062898:lavendustin A; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate