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

Curr Biol. 2000 Nov 30;10(23):1511-4. doi: 10.1016/s0960-9822(00)00825-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Embryonic Induction*
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / physiology*
  • Gene Expression Regulation, Developmental
  • Mesoderm / physiology*
  • Neurons / physiology*
  • Receptor, Fibroblast Growth Factor, Type 4
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Signal Transduction / physiology
  • Tubulin / metabolism
  • Xenopus / embryology*
  • Xenopus / genetics
  • Xenopus / metabolism

Substances

  • Receptors, Fibroblast Growth Factor
  • Tubulin
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors
  • Receptor, Fibroblast Growth Factor, Type 4