Maternal XTcf1 and XTcf4 have distinct roles in regulating Wnt target genes

Abstract

Wnt signaling pathways have essential roles in developing embryos and adult tissue, and alterations in their function are implicated in many disease processes including cancers. The major nuclear transducers of Wnt signals are the Tcf/LEF family of transcription factors, which have binding sites for both the transcriptional co-repressor groucho, and the co-activator beta-catenin. The early Xenopus embryo expresses three maternally inherited Tcf/LEF mRNAs, and their relative roles in regulating the expression of Wnt target genes are not understood. We have addressed this by using antisense oligonucleotides to deplete maternal XTcf1 and XTcf4 mRNAs in oocytes. We find that XTcf1 represses expression of Wnt target genes ventrally and laterally, and activates their expression dorsally. Double depletions of XTcf1 and XTcf3 suggest that they act cooperatively to repress Wnt target genes ventrally. In contrast, XTcf4 has no repressive role but is required to activate expression of Xnr3 and chordin in organizer cells at the gastrula stage. This work provides evidence for distinct roles for XTcfs in regulating Wnt target gene expression.