Inherited or acquired abnormalities of the gastrointestinal (GI) tract represent a large share of chronic disease in infants and children, often requiring costly long-term medical support or organ transplantation. The study of GI development aims to further the understanding of both congenital and acquired forms of pediatric gastrointestinal disease with the goal to ultimately advance therapies for GI diseases. The vertebrate body is generated from three germ layers: ectoderm, endoderm and mesoderm. The development of these three germ layers and the early reciprocal interactions between them are now well understood and accepted to be conserved between species. The lining of the vertebrate gastrointestinal tract (epithelium) is derived from the endoderm and the surrounding muscular layers and tissue are derived from the visceral mesoderm. Crosstalk between endoderm and mesoderm is critical both during development of the GI tract and for its integrity in adulthood. The epithelium has been the focus of most studies to date because of the clinical implications of epithelial biology in the understanding and treatment of cancer. Only recently has the importance of signaling from the adjacent tissue for maintenance and repair been highlighted because of the implications for stem cell biology. Likewise, the conspicuous gap in the current knowledge of GI development is how the mesodermal layer of the GI tract develops and contributes to the overall development of the GI tract. Although it has long been recognized that the mesoderm plays a major role in GI development, to date its study has been hindered by lack of appropriate tools. Our preliminary data, as well as the published evidence from other laboratories, indicate that the Wnt signaling cascade, known to play an important role in many GI cancers, plays a major role in the development and maintenance of the GI mesoderm/mesenchyme and in its interactions with the adjacent epithelial lining of the GI tract. Thus, it is the overall aim of this proposal, to examine the role of Wnt signaling in the development of the mesoderm of the GI tract . The proposed experiments will take advantage of novel tools to conditionally activate or repress Wnt signaling in the GI mesoderm of the frog embryo. The frog Xenopus laevis is a well established model of early vertebrate development because of its external development. The predicted result is that in the presence of an excess or a deficit of Wnt signaling, the GI mesoderm, and therefore GI tract, will develop abnormally. It is expected that this research will elucidate basic paradigms of GI development previously undetectable for lack of appropriate tools.