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.
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.
Kim
J
J
Laboratory of Biochemical Physiology, NCI-Frederick Cancer Research and Development Center, National Institutes of Health, Maryland 21702-1201, USA.
Lin
J J
JJ
Xu
R H
RH
Kung
H F
HF
D000818:Animals; D002384:Catalysis; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development; D005326:Fetal Proteins; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D020825:T-Box Domain Proteins; D018808:Transcription Factor AP-1 / Q000494:pharmacology / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014982:Xenopus laevis; D000098908:Brachyury Protein
D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D016222:Fibroblast Growth Factor 2; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012313:RNA; D020825:T-Box Domain Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000098908:Brachyury Protein