This proposal focuses on the mechanisms underlying the regulation of cell polarity in Xenopus Laevis. Wnt signaling, transduced through the cytoplasmic intermediate Dishevelled (Dsh), is required for many processes involving the specification of cell polarity, and inappropriate activation of Wnt signaling has been implicated in a variety of cancers. Lgl is a tumor suppressor that acts downstream of the Par6/aPKC complex in a highly conserved apical-basal polarity determination pathway. My preliminary data suggests that these 2 pathways may directly interact at the level of Dsh and Lgl.
Specific aims are 1. To define the role of Lgl in cell polarity during Xenopus development including the early ectoderm, asymmetric division of neural precursors, and convergent extension movements. 2. To analyze a role for Wnt signaling in the regulation of Lgl by modulating Wnt signaling and analyzing the effects on Lgl and other apical-basal markers, and a Structure/Function analysis of Dsh-Lgl interactions. 3. To investigate a possible role for Lgl in the Wnt/beta-catenin pathway and axis formation. Defining a mechanistic link between these 2 pathways will provide important insight into their developmental roles and their role in tumor progression.
