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 controversial [1,2]. Although FGF signalling has been implicated in early neural induction [3-5], a late role for FGFs in neural development is not well established. Indeed, it is thought that FGFs induce a precursor cell fate but are 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 that Xenopus embryos expressing ectopic FGF-8 develop an abundance of ectopic neurons that extend to the ventral, non-neural, ectoderm, but show no ectopic or enhanced notochord or somitic markers. FGF-8 inhibited the expression of an early mesoderm marker, Xbra, in contrast to eFGF, which induced ectopic Xbra robustly and neuronal differentiation weakly. The effect of FGF-8 on neurogenesis was blocked by dominant-negative FGFR-4a (DeltaXFGFR-4a). Endogenous neurogenesis was also blocked by DeltaXFGFR-4a and less efficiently by dominant-negative FGFR-1 (XFD), suggesting that it depends preferentially on signalling through FGFR-4a. The results suggest that FGF-8 and FGFR-4a signalling promotes neurogenesis and, unlike other FGFs, FGF-8 interferes with mesoderm induction. Thus, different FGFs show specificity for mesoderm induction versus neurogenesis and this may be mediated, at least in part, by the use of distinct receptors.
Hardcastle
Z
Z
Wellcome/CRC Institute, CB2 1QR,., Cambridge, UK.
Chalmers
A D
AD
Papalopulu
N
N
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004627:Embryonic Induction; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014404:Tubulin / Q000378:metabolism; D014981:Xenopus / Q000196:embryology* / Q000235:genetics / Q000378:metabolism
D017468:Receptors, Fibroblast Growth Factor; D014404:Tubulin; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D051499:Receptor, Fibroblast Growth Factor, Type 4