Directional alignment of different cell types organizes planar cell polarity

Planar cell polarity (PCP) refers to unidirectional coordination of cell polarity in the plane of epithelial tissues, whose proper formation is essential for development in various tissues. While imbalances in the amount of core PCP proteins (core proteins) between adjacent cells disrupt PCP in some tissues, other tissues maintain PCP despite containing multiple cell types with different levels of core proteins. How such tissues tolerate these imbalances remains unclear. Here, we theoretically analyzed the contribution of spatial distribution of different cell types to PCP maintenance. We adopted a previously established PCP model on two-dimensional cell sheets, where local protein-protein interactions were assumed. Our systematic simulations revealed that the patterns of cell-type distribution significantly affect the accuracy of PCP maintenance under the condition of imbalanced PCP proteins. To identify the critical patterns, we applied both deep learning techniques and statistical modeling to the simulation data. Consequently, these analyses revealed that orientation of cell-type alignment is a key aspect of cell-type distribution that affects PCP. Such directional cell-type alignment was observed in the mouse oviduct. Our findings highlight the overlooked contribution of spatial distribution of cell types to PCP maintenance in tissues with multiple cell-types.