Planar cell polarity (PCP) signaling generates subcellular asymmetry along an axis orthogonal to the epithelial apical-basal axis. Through a poorly understood mechanism, cell clones that have mutations in some PCP signaling components, including some, but not all, alleles of the receptor frizzled, cause polarity disruptions of neighboring wild-type cells, a phenomenon referred to as domineering nonautonomy. Here, a contact-dependent signaling hypothesis, derived from experimental results, is shown by reaction-diffusion, partial differential equation modeling and simulation to fully reproduce PCP phenotypes, including domineering nonautonomy, in the Drosophila wing. The sufficiency of this model and the experimental validation of model predictions reveal how specific protein-protein interactions produce autonomy or domineering nonautonomy.
Some epithelial cells display asymmetry along an axis orthogonal to the apical-basal axis, referred to as planar cell polarity (PCP). A Frizzled-mediated feedback loop coordinates PCP between neighboring cells, and the cadherin Fat transduces a global directional cue that orients PCP with respect to the tissue axes. The feedback loop can propagate polarity across clones of cells that lack the global directional signal, although this polarity propagation is error prone. Here, we show that, in the Drosophila wing, a combination of cell geometry and nonautonomous signaling at clone boundaries determines the correct or incorrect polarity propagation in clones that lack Fat mediated global directional information. Pattern elements, such as veins, and sporadic occurrences of irregular geometry are obstacles to polarity propagation. Hence, in the wild type, broad distribution of the global directional cue combines with a local feedback mechanism to overcome irregularities in cell packing geometry during PCP signaling.cell shape ͉ Fat ͉ Frizzled ͉ feedback ͉ mathematical model
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