Aim: 

Basic Fibroblast Growth Factor (bFGF) is a potent neurotrophic factor. We have previously shown that it can promote survival and neurite growth in embryonic chick ciliary ganglion neurons, and that the latter process is dependent on the activation of PLCg. In this study we have investigated the involvement of two other targets of the activated FGF receptor, ERK and PI3K.

Methods: 

The effects of the specific MEK inhibitor, PD98059, and of the PI3K inhibitor, Wortmannin, were tested on dissociated neurons in culture up to 48 h, in two different experimental conditions (laminin and laminin + 20ng/ml bFGF). Two parameters were assessed in both cases: cell survival and neurite elongation. Neurite growth was also assessed on organotypic cultures of whole ganglia.

Results: 

PD98059 (5, 25 uM) did not affect bFGF-induced survival of dissociated neurons up to 48 h, but after 24 h of treatment it significantly reduced neurite outgrowth, both on dissociated neurons and whole ganglia. Similarly, Wortmannin (10 nM) affected neurite outgrowth, but it also significantly reduced bFGF-induced neuronal survival after 48 h of treatment. Since bFGF-induced survival of chick ciliary ganglion neurons has been shown to be dependent on extracellular calcium, imaging experiments with the calcium-sensitive dye Fura-2 were performed to assess the effect of Wortmannin on calcium signals induced by bFGF at the neuronal soma. The drug reduced the amplitude of bFGF-induced responses, thus indicating that the PI3K pathway activated by bFGF is involved in the calcium dependence of neuronal survival.

Conclusions: 

ERK and PI3-K are both involved in bFGF-promoted neurite growth, while only the latter mediates neuronal survival.