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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.08.040 Byline: Iain D. Keenan (a)(c), R. Michael Sharrard (b), Harry V. Isaacs (a) Keywords: Xenopus; FGF; Cdx; ERK; PI-3 kinase; Mesoderm Abstract: Cdx homeodomain transcription factors play important roles in the development of the vertebrate body axis and gut epithelium. Signaling involving FGF, wnt and retinoic acid ligands has been implicated in the regulation of individual Cdx genes. In this study we examine the requirement for FGF-dependent signal transduction pathways in the regulation of Cdx gene expression. In the amphibian Xenopus laevis the earliest expression of Cdx1, Cdx2 and Cdx4 is within the developing mesoderm. We show that a functional FGF signaling pathway is required for the normal expression of all three amphibian Cdx genes during gastrula stages. We show that FGF stimulation activates signaling through both the MAP kinase pathway and the PI-3 kinase pathway in Xenopus tissue explants. However, our analysis of these pathways in gastrula stage embryos indicates that the MAP kinase pathway is required for Cdx gene expression, whereas the PI-3 kinase pathway is not. We show that FGF and wnt signaling can interact in the regulation of Cdx genes and during gastrula stages the normal expression of the Cdx genes requires the activity of both pathways. Furthermore, we show that wnt mediated Cdx regulation is independent of the MAP kinase pathway. Author Affiliation: (a) Area 11, Department of Biology, University of York, York, YO10 5YW, UK (b) YCR Cancer Research Unit, Department of Biology, University of York, York, YO10 5YW, UK (c) Molecular Pharmacology Unit, Cancer Research UK, Biomedical Research Centre, Ninewells Hospital, Dundee, DD1 5SY, UK Article History: Received 19 September 2005; Revised 7 August 2006; Accepted 21 August 2006

The effects of fibroblast growth factor signaling on expression of Xenopus caudal type homeo box genes are presented.

Cdx homeodomain transcription factors have multiple roles in early vertebrate development. Furthermore, mis-regulation of Cdx expression has been demonstrated in metaplasias and cancers of the gut epithelium. Given the importance of Cdx genes in development and disease, the mechanisms underlying their expression are of considerable interest. We report an analysis of the upstream regulatory regions from the amphibian Xenopus laevis Cdx4 gene. We show that a GFP reporter containing 2.8 kb upstream of the transcription start site is expressed in the posterior of transgenic embryos. Deletion analysis of the upstream sequence reveals that a 247-bp proximal promoter fragment will drive posterior expression in transgenic embryos. We show that 63 bp of upstream sequence, that includes a consensus site for POU-domain octamer-binding proteins, retains significant promoter activity. Co-expression of the octamer-binding protein Oct1 induces expression from a Cdx4 reporter and mutation of the octamer site abolishes activity of the same reporter. We show that the octamer site is highly conserved in the promoters of the human, mouse, chicken, and zebrafish Cdx4 genes and within the promoters of amphibian Cdx1 and Cdx2. These data suggest a conserved function for octamer-binding proteins in the regulation of Cdx family members. Keywords: Xenopus; Cdx4; POU-domain; Oct1