Maternal Wnt/ß-catenin signaling coactivates transcription through NF-κB binding sites during Xenopus axis formation.

Maternal Wnt/ß-Catenin signaling establishes a program of dorsal-specific gene expression required for axial patterning in Xenopus. We previously reported that a subset of dorsally expressed genes depends not only on Wnt/ß-Catenin stimulation, but also on a MyD88-dependent Toll-like receptor/IL1-receptor (TLR/IL1-R) signaling pathway. Here we show that these two signal transduction cascades converge in the nucleus to coactivate gene transcription in blastulae through a direct interaction between ß-Catenin and NF-κB proteins. A transdominant inhibitor of NF-κB, ΔNIκBα, phenocopies loss of MyD88 protein function, implicating Rel/NF-κB proteins as selective activators of dorsal-specific gene expression. Sensitive axis formation assays in the embryo demonstrate that dorsalization by Wnt/ß-Catenin requires NF-κB protein activity, and vice versa. Xenopus nodal-related 3 (Xnr3) is one of the genes with dual ß-Catenin/NF-κB input, and a proximal NF-κB consensus site contributes to the regional activity of its promoter. We demonstrate in vitro binding of Xenopus ß-Catenin to several XRel proteins. This interaction is observed in vivo upon Wnt-stimulation. Finally, we show that a synthetic luciferase reporter gene responds to both endogenous and exogenous ß-Catenin levels in an NF-κB motif dependent manner. These results suggest that ß-Catenin acts as a transcriptional co-activator of NF-κB-dependent transcription in frog primary embryonic cells.

Vertebrate Rel proteins exhibit Dorsal-like activities in early Drosophila embryogenesis.

In Drosophila, the Toll/Dorsal pathway triggers the nuclear entry of the Rel protein Dorsal, which controls dorsoventral patterning in early embryogenesis and plays an important role in innate immunity of the adult fly. In vertebrates, the homologous Toll/IL-1 receptor signaling pathway directs the nuclear localization of Rel/NF-kappaB complexes, which activate genes involved in proliferation, apoptosis, and immune response. Recently, first evidence has been reported for the activity of vertebrate Rel proteins and a Toll-like signaling pathway in the dorsoventral patterning process of Xenopus laevis embryos. Given the evolutionary divergence of the fly and frog model organisms, these findings raise the question, to what extent the effector functions of this pathway have been conserved? Here, we report the ability of two Xenopus Rel proteins to partially substitute for several, but not all, functions of the Dorsal protein in Drosophila embryos. Our results suggest the interaction between Rel proteins and their cytoplasmic inhibitors as an important interface of evolutionary adaptation.