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The Role of Intracellular Interactions in the Collective Polarization of Tissues and its Interplay with Cellular Geometry

Planar cell polarity (PCP), the coherent in-plane polarization of a tissue on multicellular length scales, provides directional information that guides a multitude of developmental processes at cellular and tissue levels. While it is manifest that cells utilize both intracellular and intercellular mechanisms, how the two produce the collective polarization remains an active area of investigation. We study the role of intracellular interactions in the large-scale spatial coherence of cell polarities, and scrutinize the role of intracellular interactions in the emergence of tissue-wide polarization. We demonstrate that nonlocal cytoplasmic interactions are necessary and sufficient for the robust long-range polarization, and are essential to the faithful detection of weak directional signals. In the presence of nonlocal interactions, signatures of geometrical information in tissue polarity become manifest. We investigate the deleterious effects of geometric disorder, and determine conditions on the cytoplasmic interactions that guarantee the stability of polarization. These conditions get progressively more stringent upon increasing the geometric disorder. Another situation where the role of geometrical information might be evident is elongated tissues. Strikingly, our model recapitulates an observed influence of tissue elongation on the orientation of polarity. Eventually, we introduce three classes of mutants: lack of membrane proteins, cytoplasmic proteins, and local geometrical irregularities. We adopt core-PCP as a model pathway, and interpret the model parameters accordingly, through comparing the in silico and in vivo phenotypes. This comparison helps us shed light on the roles of the cytoplasmic proteins in cell-cell communication, and make predictions regarding the cooperation of cytoplasmic and membrane proteins in long-range polarization.