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. [References: 45]

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