Two negative regulators of Wingless signaling, dAPC2 and Zeste-White 3, also play a role in the organization of the preblastoderm cytoskeleton. B.M. McCartney 1, A. Bejsovec 2, M. Peifer 1. 1) Department of Biology, University of North Carolina, Chapel Hill, NC; 2) Developmental, Cell and Molecular Biology Group, Duke University, Durham, NC.
Like their vertebrate homologues, Drosophila adenomatous polyposis coli (APC) proteins negatively regulate Wingless/Wnt signal transduction, functioning as components of a complex which targets b-catenin/Armadillo (Arm) for destruction. In cultured cells, vertebrate APC associates with the cell cortex and the microtubule cytoskeleton, suggesting that APC has additional functions in the cell that may include regulation of the cytoskeleton. Consistent with this hypothesis, we have shown that there is a striking co-localization of Drosophila APC2 (dAPC2) with the actin cytoskeleton in many tissues including the preblastoderm embryo, where the proper interaction of the actin and microtubule cytoskeletons is crucial for normal syncitial mitoses. To determine whether dAPC2, or its partner in the Arm destruction complex, Zeste-White 3 (Zw3), have roles in the normal development of the preblastoderm embryo, we conducted phenotypic studies of preblastoderm embryos maternally and zygotically mutant for either dAPC2 or zw3. These studies revealed that a significant proportion of mutant embryos exhibit defects consistent with perturbations of the cytoskeleton, including misalignment of spindles and nuclear fall out from the cortex. Our current understanding of dAPC2 and Zw3 function in the development of segment polarity suggests that their influence on the preblastoderm cytoskeleton could be either Arm dependent or Arm independent. We are currently pursuing experiments to distinguish between these possibilities, and to begin to define the mechanism for dAPC2 and Zw3 activity in organizing the cytoskeleton in the early embryo.