Asymmetric Dishevelled localization mediates Planar Cell Polarity signaling. J.D. Axelrod. Dept Pathology, Stanford Univ Sch Medicine, Stanford, CA.

   In Drosophila, many adult epithelia acquire a polarity orthogonal to the apical-basal axis, known as planar cell polarity [PCP], or tissue polarity. On a wild type wing, this is manifest as a polarized array of trichomes, each of which arises from the distal vertex of the cell and is oriented distally. PCP is regulated by a presumptive Wnt mediated signaling pathway, utilizing Frizzled (Fz) as a receptor and Dishevelled (Dsh) as a transducer. Downstream of Dsh, The PCP pathway activates a signaling cascade that is distinct from the Wingless (Wnt-1) pathway. Activation of this pathway directly regulates cytoskeletal architecture by positioning the developing actin rich prehair at the distal vertex. We have studied the mechanism by which Fz signaling results in cellular asymmetry. Previous results using a heterologous system indicated that Fz recruits Dsh to the membrane. We now demonstrate that Dsh displays a dynamic pattern of subcellular localization in vivo. After an early phase of symmetric, subapical membrane localization, Dsh migrates to the distal surface of the cell, and finally localizes to an apical patch at the distal vertex, preceding outgrowth of the prehair from this location. We will present evidence that the Fz signal directs this subcellular localization of Dsh. Furthermore forced relocalization of Dsh redirects prehair formation and therefore polarity. We conclude that Fz dependent Dsh localization is the event that confers asymmetry by marking the distal vertex as the site of prehair initiation. We will describe additional controls governing the distribution of Dsh, and discuss the implications of these observations with respect to the properties of the as yet unidentified PCP ligand.