Alternative adrenal chromaffin cell fates induced by basic fibroblast growth factor or cyclic AMP in vitro depend on...

Basic fibroblast growth factor stimulates cultured adrenal chromaffin cells to divide and to transform into sympathetic neurons, but the efficacies reported for these actions of basic fibroblast growth factor have varied widely. We have examined the effect of various growth substrates on basic fibroblast growth factor responses and here we show that the ability of basic fibroblast growth factor to transform neonatal rat chromaffin cells into sympathetic neurons depends on laminin as the culture substrate. On collagen, less than 5% of the cells were transformed into neurons by basic fibroblast growth factor, even when the culture was supplemented with heparin or heparan sulphate, but 65% of cells entered the S phase in the presence of basic fibroblast growth factor 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 concentrations of basic fibroblast growth factor, suggesting that an overlapping pool of cells change their phenotype depending on growth substrate. The cyclic AMP analogue 8-(4-chlorophenylthio)cyclic AMP apparently mimicked the actions of basic fibroblast growth factor, promoting neuronal differentiation on laminin, but mitogenic stimulation on collagen. These data support the notion that collagen and laminin promote different instructions in chromaffin cells that can collaborate with the signals induced by basic fibroblast growth factor and 8-(4-chlorophenylthio)cyclic AMP to determine chromaffin or neuronal cell fates.