INVOLVEMENT OF NF-KAPPA-B ASSOCIATED PROTEINS IN FGF-MEDIATED MESODERM INDUCTION

In this report, we have used mRNA injection to study the action of mut ants of XrelA, a Xenopus homolog of the RelA (p65) component of NF-kap pa B, on the induction of mesoderm in Xenopus embryos. A region of the res homology domain of XrelA was deleted to create XrelA Delta SP, wh ich retains the dimerization and activation domains, but no longer bin ds to DNA, We also made an analogous derivative of mammalian NF-kappa B1 (p50), We show that both constructs have dominant inhibitory activi ty. When message encoding ei;ther is injected into eggs or oocytes, DN A binding of rel family members is suppressed, as is transactivation o f a kappa B-dependent promoter in embryos. Expression of XrelA Delta S P in animal caps blocks the induction of mesoderm by bFGF. In addition , this mutant prevents elongation movements generated by activin, but has little effect on posterior dorsal cytodifferentiation, which in ma rked contrast is blocked by inhibition of the FGF signal transduction pathway between the receptor and MAP kinase, The specificity of the Xr elA Delta SP effect on FGF signaling is shown by rescue of mesodermal marker expression when XrelA Delta SP is coexpressed with a specific r el inhibitor. The target of these dominant negative constructs seems t o be neither XrelA itself, nor p50, but rather some other molecule wit h which XrelA, rather than NF-kappa B1, heterodimerizes. We show that XrelA Delta SP blocks FGF induction of mesoderm downstream of MAP kina se and Xbra expression. Thus it prevents the maintenance of Xbra expre ssion by inhibiting its autoregulation by embryonic FGF (eFGF). We sug gest that XrelA Delta SP differs from other reported inhibitors of FGF signaling because it inhibits only gastrula stage FGF signaling and n ot the maternally programmed signaling at the blastula stage, Our resu lts therefore suggest that zygotic FGF action is required for cell mov ements rather than dorsal differentiation.