FGF-8 stimulates neuronal differentiation through FGFR-4a and interferes with mesoderm induction in Xenopus embryos

The role of fibroblast growth factors (FGFs) in neural induction is controv ersial [1,2]. Although FGF signalling has been implicated in early neural i nduction [3-5], a late role for FGFs in neural development is not well esta blished. Indeed, it is thought that FGFs induce a precursor cell fate but a re not able to induce neuronal differentiation or late neural markers [6-8] . It is also not known whether the same or distinct FGFs and FGF receptors (FGFRs) mediate the effects on mesoderm and neural development. We report t hat Xenopus embryos expressing ectopic FGF-8 develop an abundance of ectopi c neurons that extend to the ventral, non-neural, ectoderm, but show no ect opic or enhanced notochord or semitic markers. FGF-8 inhibited the expressi on of an early mesoderm marker, Xbra, in contrast to eFGF, which induced ec topic Xbra robustly and neuronal differentiation weakly. The effect of FGF- 8 on neurogenesis was blocked by dominant-negative FGFR-4a (Delta XFGFR-4a) . Endogenous neurogenesis was also blocked by Delta XFGFR-4a and less effic iently by dominant-negative FGFR-1 (XFD), suggesting that it depends prefer entially on signalling through FGFR-4a. The results suggest that FGF-8 and FGFR-4a signalling promotes neurogenesis and, unlike other FGFs, FGF-8 inte rferes with mesoderm induction. Thus, different FGFs show specificity for m esoderm induction versus neurogenesis and this may be mediated, at least in part, by the use of distinct receptors.