Wnt signaling meets internal dissent.

In canonical Wnt signaling, β-catenin translocates to the cell nucleus, interacting with Tcf/Lef factors to activate transcription of Wnt target genes. In this issue of Genes & Development, Vacik and colleagues (pp. 1783-1795) report that a highly conserved sequence in intron 5 of Tcf7l2 conceals an internal promoter region that, when activated by Vax2, drives transcription of truncated Tcf7l2 mRNAs. The encoded Tcf7l2 protein binds to DNA, but not β-catenin, and therefore acts as a dominant-negative Wnt antagonist.