Revisiting the role of Wnt signaling in sensory organ development in the Drosophila wing. Ezgi Kunttas-Tatli, Kellie Kravarik, Sandra Zimmerman, Amy Fuller, Brooke M. McCartney. Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA.

   The colon cancer tumor suppressor Adenomatous polyposis coli (APC) negatively regulates Wnt signal transduction through its activity in the destruction complex. APC binds directly to the main effector of the pathway, -catenin (Armadillo in Drosophila), and targets it for proteosome-mediated degradation. The disruption of APC (both APC1 and APC2) is implicated in the initiation of >80% of human colon cancers. In addition to its role in Wnt signaling, APC acts as a cytoskeletal regulator, although it is less clear how the disruption of these cytoskeletal functions contributes to tumorigenesis. To understand how disruption of APC affects epithelial tissues, we are using the developing wing epithelium as a model. We previously showed in the larval wing disc that the complete loss of APC in clones results in apical constriction and invagination through activation of canonical Wnt targets, RhoI and Myosin II. We are currently investigating the long-term effects of APC loss and Wnt pathway activation on the development of the wing epithelium and its sensory organs. We have found that activation of the Wnt pathway by either loss of APC, expression of a stabilized form of Armadillo (Arm^S10), or manipulation of Shaggy (GSK3) leads to the development of ectopic sensory organs in the anterior and posterior blade consistent with previous results. Activation of excessive Wnt signaling at the anterior margin results in cell fate changes and spacing defects that may reveal novel Wnt dependent changes in gene regulation. Surprisingly, APC null clones in the posterior compartment exhibit innervated sensory organs in contrast to the non-innervated sensory organs at the wild type posterior margin. We are currently testing the hypothesis that this innervation and the cell fate transformations at the anterior margin are the result of changes in the expression of Wnt targets Senseless, Achaete and Scute.