title: Cdx4 is a direct target of the canonical Wnt pathway.
abstract: There is considerable evidence that the Cdx gene products impact on vertebral patterning by direct regulation of Hox gene expression. Data from a number of vertebrate model systems also suggest that Cdx1, Cdx2 and Cdx4 are targets of caudalizing signals such as RA, Wnt and FGF. These observations have lead to the hypothesis that Cdx members serve to relay information from signaling pathways involved in posterior patterning to the Hox genes. Regulation of Cdx1 expression by RA and Wnt in the mouse has been well characterized; however, the means by which Cdx2 and Cdx4 are regulated is less well understood. In the present study, we present data suggesting that Cdx4 is a direct target of the canonical Wnt pathway. We found that Cdx4 responds to exogenous Wnt3a in mouse embryos ex vivo, and conversely, that its expression is down-regulated in Wnt3a(vt/vt) embryos and in embryos cultured in the presence of Wnt inhibitors. We also found that the Cdx4 promoter responds to Wnt signaling in P19 embryocarcinoma cells and have identified several putative LEF/TCF response elements mediating this effect. Consistent with these data, chromatin immunoprecipitation assays from either embryocarcinoma cells or from the tail bud of embryos revealed that LEF1 and beta-catenin co-localize with the Cdx4 promoter. Taken together, these results suggest that Cdx4, like Cdx1, is a direct Wnt target.
authors.affiliation: Institut de Recherches Cliniques de Montréal, Québec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pilon
authors.forename: Karen
authors.initials: K
authors.lastname: Oh
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Sylvestre
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bouchard
authors.forename: Joanne
authors.initials: J
authors.lastname: Savory
authors.forename: David
authors.initials: D
authors.lastname: Lohnes
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D004622:Embryo, Mammalian / Q000737:chemistry / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020218:Response Elements; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D051176:beta Catenin / Q000032:analysis / Q000378:metabolism
chemical_list: C084563:Cdx4 protein, mouse; D018398:Homeodomain Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin