A Synthetic Planar Cell Polarity System Reveals Localized Feedback on Fat4-Ds1 Complexes

Planar cell polarity (PCP) is the process by which sheets of cells, typically in the form of epithelial cell layers, acquire an orientation within the plain of the sheet. Recent studies highlighted the role of the atypical cadherins Fat (Ft) and Dachsous (Ds) in this process. Models of PCP suggest that planar polarity can arise from these interactions through localized positive feedbacks between Ft-Ds complexes pointing either in the same direction or in opposite directions. However, neither such feedback mechanisms nor the molecular processes underlying these feedbacks have been identified. To address these questions, we developed a synthetic biology platform, based on a mammalian cell culture system expressing different variants of Fat4 and Ds1. We used various imaging techniques to quantitatively study the interactions between Fat4 and Ds1. Our results suggest Fat4-Ds1 complexes accumulate on the cell boundaries in a threshold-like non-linear manner, consistent with a positive feedback model. We further show that Fat4-Ds1 complexes form extremely stable boundary complexes, suggesting localized feedback through stabilization of interacting complexes. Finally, we show that cells expressing both Fat4 and Ds1 exhibit spontaneous polarization of Fat4-Ds1 boundary accumulation. Taken together, our results suggest that localized feedbacks on Fat4-Ds1 complexes, can underlie planar cell polarity.