Cluster Assembly Dynamics Drive Fidelity of Planar Cell Polarity Polarization

The planar cell polarity (PCP) signaling pathway polarizes epithelial cells in the tissue plane by segregating distinct molecular subcomplexes to opposite sides of each cell, where they interact across intercellular junctions to form asymmetric clusters. The role of clustering in this process is unknown. We hypothesized that protein cluster size distributions could be used to infer the underlying molecular dynamics and function of cluster assembly and polarization. We developed a method to count the number of monomers of core PCP proteins within individual clusters in live animals, and made measurements over time and space in wild type and in strategically chosen mutants. The data demonstrate that clustering is required for polarization, and together with mathematical modeling provide evidence that cluster assembly dynamics dictate that larger clusters are more likely to be strongly asymmetric and correctly oriented. We propose that cluster assembly dynamics thereby drive fidelity of cell- and tissue-level polarization.