Novel Functions of dAPC2 in Cytoskeletal Organization and Cell Fate. K.A. Akong , B.M. McCartney , M.A. Peifer. Department of Biology, University of North Carolina, Chapel Hill, NC.
The Adenomatous Polyposis Coli (APC) tumor suppressor protein has many proposed cellular functions. The most well known role of APC is as a negative regulator of the Wnt/Wg signaling pathway. APC forms part of the "destruction complex", together with GSK-3b/Zw-3 and Axin. This complex targets cytoplasmic b-catenin/Armadillo for proteosomal degredation. APC has also been shown to associate with cytoskeletal structures, such as microtubules and microfilaments. In Drosophila, there are two APC genes. The first to be characterized, dAPC, is predominantly expressed in the nervous system, and mutants exhibit a retinal degeneration phenotype. dAPC2 is more widely expressed throughout development. Our initial studies of the expression pattern of dAPC2 showed a striking asymmetric localization in neuroblasts, a CNS stem cell. Neuroblasts are known to undergo asymmetric cell divisions, with an oriented mitotic spindle, to give rise to a smaller ganglion mother cell (GMC), and a regenerated neuroblast stem cell. We are studying the larval neuroblasts in more detail, comparing the localization of dAPC2 to other asymmetrically localized proteins, such as Miranda, Prospero, Bazooka and Inscuteable, in various mutant backgrounds. We are also examining the effects on the cytoskeleton and asymmetric cell divisions of removing dAPC2, and of simultaneously removing both dAPC and dAPC2.