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 facto r (bFGF) on morphogenesis of rat hippocampal neurons in dissociated ce ll culture. As a result, we found that bFGF selectively promoted the b ifurcation and growth of axonal branches without affecting the elongat ion rate of primary axons. The dendritic outgrowth was rather inhibite d by bFGF. These effects of bFGF resulted in increased complexity of a xonal trees. The effect of bFGF was concentration dependent (0.1-10 ng /ml) and was abolished by the presence of anti-bFGF neutralizing antib ody. The accelerated axonal branch formation in the presence of bFGF w as restored to the basil rate following removal of bFGF, suggesting th at the action of bFGF is reversible and that the continuous presence i s 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 t reatment with heparitinase and by tyrosine kinase inhibitors, herbimyc in A and lavendustin A, indicating the importance of heparan sulfate a nd tyrosine kin ase in bFGF signal transduction. Treatment with a prot ein kinase C activator phorbol-12-myristate-13-acetate did not signifi cantly affect the neurite branching, and the action of bFGF was not bl ocked by a protein kinase C inhibitor staurosporine. Protein kinase C is unlikely to play a role in branch formation. The novel action of bF GF as a regulator of axonal branching must be a particularly useful mo del for the study of neuritogenesis and synaptogenesis. of brain neuro ns.