Cluster assembly dynamics drive fidelity of planar cell polarity polarization.

Planar cell polarity (PCP) signaling orients epithelial cells along an in-plane tissue axis and is a required feature of embryonic development in bilaterians. In PCP signaling, distinct molecular subcomplexes segregate to opposite sides of each cell, where they interact across intercellular junctions to form highly polarized clusters. How signal amplification and error correction occur to achieve the observed level of asymmetry is not known. Here, we used quantitative photobleaching to quantify the number of monomers of core PCP proteins within individual clusters in living Drosophila pupal wings. These data, combined with mathematical modeling, allowed us to determine how the growth of PCP signaling complexes is coupled to robust and accurate polarization. We find that clusters become increasingly polarized and correctly oriented as they become larger. Further, mutations that inhibit cluster growth inhibit cell- and tissue-level polarization, confirming that a population of large clusters is required for successful polarization. Our results reveal how cluster assembly provides the signal amplification and error correction necessary for robust polarization at the molecular, and hence cellular and tissue, levels, a mechanism that may apply to the many signal transduction pathways that feature the assembly of large, nonstoichiometric signalosomes.