Abstract
The reciprocal and highly regulated processes of cellular proliferation, cellular differentiation, and progression to a postmitotic state during embryogenesis generate the cellular diversity in the developing nervous system. Growth factors, in part, can regulate these proliferative or differentiation processes by analogous mechanisms. Basic fibroblast growth factor (bFGF), a member of FGF family, has broad biological functions involving the regulation of cell growth, differentiation, and proliferation. As extension and remodeling of neurites play essential roles in development and neuronal plasticity, we investigated a role for nerve growth factor receptor (NGFR) on bFGF-induced neurite outgrowth in rat pheochromocytoma cell line, PC12. Our goal in the present study was to determine if there is a causal link between bFGF and NGFR. Results of these studies indicate that bFGF is required for NGFR-induced changes in morphology and transcriptional induction of the gene. We have provided convincing evidence that inhibitor of bFGF, PD173074, completely inhibited NGFR protein expression, whereas it partially blocked the NGFR protein expression in response to bFGF in PC12 cells. Another important finding of our study provides the data on the involvement of bFGF in MAPK-dependent signaling pathways and neurite outgrowth in PC12 cells, which suggests a central role of MAPK in the neuronal induction by bFGF. Taken together, these results raise the possibility that bFGF activates a MAPK-mediated pathway related to NGFR expression.
