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*
- From the ‡Laboratory of Biochemical Physiology, Division of Basic Science, NCI-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, Maryland 21702-1201 and the §Intramural Research and Support Program, Science Applications International Corporation, Frederick, Maryland 21702-1201
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-fostogether, 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.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵¶ To whom correspondence should be addressed. Tel.: 301-846-5703; Fax: 301-846-6863; E-mail: Kungh{at}mail.ncifcrf.gov.
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↵1 The abbreviations used are: FGF, fibroblast growth factor; bFGF, basic fibroblast growth factor; eFGF, embryonic fibroblast growth factor; DN-jun, dominant-negative mutant of jun; DN-FR, dominant-negative mutant of the FGF receptor; DN-Xbra, dominant-negative mutant of Xenopus brachuary (Xbra-Engrailed); DN-ras, dominant-negative mutant ofras; RT-PCR, reverse transcription-polymerase chain reaction; EF-1α, elongation factor-1α; DMZ, dorsal marginal zone; VMZ, ventral marginal zone.
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↵2 J. Kim and H.-f. Kung, unpublished data.
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- Received December 11, 1996.
- Revision received September 10, 1997.
- The American Society for Biochemistry and Molecular Biology, Inc.
