Inhibition of Wnt signaling in foregut development

Children'S Hospital Med Ctr (Cincinnati), Cincinnati OH

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Abstract

DESCRIPTION (provided by applicant): Pediatric gastroenterologists often turn to developmental biology for answers about clinical conditions and syndromes affecting the liver and proximal gastrointestinal tract. Little is known about the molecular basis of embryonic liver and foregut development in vertebrates. It has been shown that pre-cardiac mesoderm induces an area of the anterior endoderm to differentiate into liver. How the anterior endoderm becomes competent to respond to these signals is unclear. There is evidence in both Xenopus and mouse that anterior endoderm expresses Wnt antagonists. This suggests that the cells fated to become foregut and liver are exposed to secreted Wnt antagonists prior to the inductive signals from the cardiac mesoderm. We reasoned Wnt signaling needs to be inhibited in the anterior endoderm for normal foregut and liver development to occur. The aim of this proposal is to test the hypothesis that inhibition of Wnt signaling at the gastrula stage of development is necessary for the development of normal foregut and its derivatives and sufficient to initiate foregut development.