ALTERNATIVE ADRENAL CHROMAFFIN CELL FATES INDUCED BY BASIC FIBROBLASTGROWTH-FACTOR OR CYCLIC-AMP IN-VITRO DEPEND ON A COLLABORATION WITH THE GROWTH SUBSTRATE

Basic fibroblast growth factor stimulates cultured adrenal chromaffin cells to divide and to transform into sympathetic neurons, but the eff icacies reported for these actions of basic fibroblast growth factor h ave varied widely. We have examined the effect of various growth subst rates on basic fibroblast growth factor responses and here we show tha t the ability of basic fibroblast growth factor to transform neonatal rat chromaffin cells into sympathetic neurons depends on laminin as th e culture substrate. On collagen, less than 5% of the cells were trans formed into neurons by basic fibroblast growth factor, even when the c ulture was supplemented with heparin or heparan sulphate, but 65% of c ells entered the S phase in the presence of basic fibroblast growth fa ctor compared to 15% in its absence, showing that the basic fibroblast growth factor receptor is still active. On laminin, by contrast, over 60% of the cells transformed into neurons in response to the same con centrations of basic fibroblast growth factor, suggesting that an over lapping pool of cells change their phenotype depending on growth subst rate. The cyclic AMP analogue 8-(4-chlorophenylthio)cyclic AMP apparen tly mimicked the actions of basic fibroblast growth factor, promoting neuronal differentiation on laminin, but mitogenic stimulation on coll agen. These data support the notion that collagen and laminin promote different instructions in chromaffin cells that can collaborate with t he signals induced by basic fibroblast growth factor and 8-(4-chloroph enylthio)cyclic AMP to determine chromaffin or neuronal cell fates.