Wnt/beta-catenin signaling regulates the expression of the homeobox gene Cdx1 in embryonic intestine

During mammalian development, the Cdx1 homeobox gene exhibits an early peri od of expression when the embryonic body axis is established, and a later p eriod where expression is restricted to the embryonic intestinal endoderm, Cdx1 expression is maintained throughout adulthood in the proliferative cel l compartment of the continuously renewed intestinal epithelium, the crypts , In this study, we provide evidence in vitro and in vivo that Cdx1 is a di rect transcriptional target of the Wnt/beta-catenin signaling pathway, Upon Wnt stimulation, expression of Cdx1 can be induced in mouse embryonic stem (ES) cells as well as in undifferentiated rat embryonic endoderm, Tcf4-def icient mouse embryos show abrogation of Cdx1 protein in the small intestina l epithelium, making Tcf4 the likely candidate to transduce Wnt signal in t his part of gut. The promoter region of the Cdx1 gene contains several Tcf- binding motifs, and these bind Tcf/Lef1/beta-catenin complexes and mediate beta-catenin-dependent transactivation, The transcriptional regulation of t he homeobox gene Cdx1 in the intestinal epithelium by Wnt/beta-catenin sign aling underlines the importance of this signaling pathway in mammalian endo derm development.