Mesoderm induction by heterodimeric AP-1 (c-Jun and c-Fos) and its involvement in mesoderm formation through the embryonic fibroblast growth factor/Xbra autocatalytic loop during the early development of Xenopus embryos

J Biol Chem. 1998 Jan 16;273(3):1542-50. doi: 10.1074/jbc.273.3.1542.

Abstract

We have previously demonstrated the involvement of AP-1/Jun in fibroblast growth factor (FGF) signaling by loss-of-function assay (Dong, Z., Xu, R.-H., Kim, J., Zhan, S.-N., Ma, W.-Y., Colburn, N. H., and Kung, H. (1996) J. Biol. Chem. 271, 9942-9946). Further investigations by gain-of-function are reported in this study. AP-1 transactivation activity was increased by the treatment of animal cap explants with FGF. Ectopic overexpression of two components of AP-1 (c-jun and c-fos together, but not alone) produced posteriorized embryos and induced mesoderm formation in animal cap explants, indicating that both AP-1 heterodimers are required for mesoderm induction. Since Ras/AP-1 functions downstream of FGF signaling, we then tested the involvement of Ras/AP-1 in mesoderm maintenance mediated by embryonic FGF/Xbra using dominant-negative mutants. Mesoderm maintenance mediated by embryonic FGF/Xbra was blocked by dominant-negative mutants of Ras/AP-1, and AP-1 enhanced the expression of Xbra. Further studies demonstrated the inhibition of Ras/AP-1-mediated mesoderm formation by dominant-negative mutants of the FGF receptor and Xbra. These results indicate that Ras/AP-1 and FGF/Xbra signals are involved in the mesoderm maintenance machinery and mesoderm formation through the synergistic action of the diversified signal pathways derived from the FGF/Xbra autocatalytic loop.

MeSH terms

  • Animals
  • Catalysis
  • Culture Techniques
  • DNA-Binding Proteins / physiology*
  • Embryo, Nonmammalian / drug effects
  • Embryonic Development*
  • Fetal Proteins*
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 2 / physiology*
  • Mesoderm / drug effects
  • Mesoderm / physiology*
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / pharmacology
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / pharmacology
  • RNA / metabolism
  • T-Box Domain Proteins*
  • Transcription Factor AP-1 / pharmacology
  • Transcription Factor AP-1 / physiology*
  • Transcription Factors / physiology*
  • Xenopus laevis

Substances

  • DNA-Binding Proteins
  • Fetal Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • T-Box Domain Proteins
  • Transcription Factor AP-1
  • Transcription Factors
  • Fibroblast Growth Factor 2
  • RNA
  • Brachyury protein