The Wnt Pathway and Inductive Competence in Early Xenopus Development

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0110893WilsonInductive signals between cell populations govern much of embryonic development. A central feature of these interactions is changing competence: the response of cells to particular signaling ligands evolves in a complex and precisely regulated manner. The long-term goal of the proposed research is to understand the molecular basis of competence, using changing responses to Wnt signaling in early Xenopus development as a model. In the first hours of Xenopus development, activation of the Wnt signaling pathway drives formation of the dorsal axis; only a few hours later, this response is lost, and the pathway instead functions in mesodermal and neural patterning. The objectives of the current project are to understand why an important target gene, siamois, is activated by early but not by late Wnt signaling, and to tie competence of the Wnt pathway to induce this gene to the broader embryological response, dorsal axis formation. Using a simple promoter-reporter assay, the siamois promoter will be analyzed to identify sequence elements important in the loss of Wnt responsiveness at later stages. Competence of siamois itself to induce a dorsal axis will then be examined using inducible activated and inhibitory versions of siamois, thus linking the regulation of this gene to axis induction competence. Both aims will make use of a newly developed tool for inducible stimulation of Wnt responses, consisting of a dexamethasone-inducible, activated form of XTCF3, a DNA-binding protein known to mediate transcriptional responses to Wnt signaling. This work will contribute to elucidating the mechanism of inductive competence, an important and long-standing problem in developmental biology.