Evidence for positive and negative regulation of the mouse Cdx2 gene

The caudal family of transcription factors specifies posterior structures during mouse development. We describe the cis-regulatory regions that control mouse Cdx2 expression in the posterior neural tube and mesoderm. An 11.4 kb genomic fragment directs reporter gene expression in a pattern reflecting endogenous Cdx2 expression. A crucial enhancer is located in a 1 kb fragment upstream of the Cdx2 transcriptional start site. This enhancer by itself directs reporter gene expression to more anterior levels in the neural tube compared to the endogenous Cdx2 expression, suggesting the presence of negative regulatory elements outside the 1 kb fragment. A second enhancer, located in the first intron directs robust expression to the posterior two-thirds of the developing embryo in a pattern that is ectopic to Cdx2 expression. The intronic enhancer activity is silenced in the context of the larger 11.4 kb reporter construct. Intron 1 contains two independent enhancers that specifically direct expression to mesoderm (MSE) and neural tube (NSE). Phylogenetic comparison of vertebrate Cdx2 sequences indicates several conserved regions of sequences within the three-enhancer regions. A transcription factor database search suggests potential binding sites for factors involved in FGF and Wnt signaling pathways.