ALTERNATIVE ADRENAL CHROMAFFIN CELL FATES INDUCED BY BASIC FIBROBLASTGROWTH-FACTOR OR CYCLIC-AMP IN-VITRO DEPEND ON A COLLABORATION WITH THE GROWTH SUBSTRATE
Ch. Chu et Am. Tolkovsky, ALTERNATIVE ADRENAL CHROMAFFIN CELL FATES INDUCED BY BASIC FIBROBLASTGROWTH-FACTOR OR CYCLIC-AMP IN-VITRO DEPEND ON A COLLABORATION WITH THE GROWTH SUBSTRATE, Neuroscience, 59(1), 1994, pp. 43-54
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.