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Citation
Shadkhoo, S., Mani, M. (2019). The role of intracellular interactions in the collective polarization of tissues and its interplay with cellular geometry.  PLoS Comput. Biol. 15(11): e1007454.
FlyBase ID
FBrf0244864
Publication Type
Research paper
Abstract
Planar cell polarity (PCP), the long-range in-plane polarization of epithelial tissues, 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 interactions, the coupling between the two modules, essential to the coordination of collective polarization, remains an active area of investigation. We propose a generalized reaction-diffusion model to study the role of intracellular interactions in the emergence of long-range polarization, and show that the nonlocality of cytoplasmic interactions, i.e. coupling of membrane proteins localized on different cell-cell junctions, is of vital importance to the faithful detection of weak directional signals, and becomes increasingly more crucial to the stability of polarization against the deleterious effects of large geometric irregularities. We demonstrate that nonlocal interactions are necessary for geometric information to become accessible to the PCP components. The prediction of the model regarding polarization in elongated tissues, is shown to be in agreement with experimental observations, where the polarity emerges perpendicular to the axis of elongation. Core PCP is adopted as a model pathway, in term of which we interpret the model parameters. To this end, we introduce three distinct classes of mutations, (I) in membrane proteins, (II) in cytoplasmic proteins, and (III) local enhancement of geometric disorder. Comparing the in silico and in vivo phenotypes, we show that our model successfully recapitulates the salient phenotypic features of these mutations. Exploring the parameter space helps us shed light on the role of cytoplasmic proteins in cell-cell communications, and make falsifiable predictions regarding the cooperation of cytoplasmic and membrane proteins in the establishment of long-range polarization.
PubMed ID
PubMed Central ID
PMC6903760 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Comput. Biol.
    Title
    PLoS Computational Biology
    Publication Year
    2005-
    ISBN/ISSN
    1553-7358 1553-734X
    Data From Reference
    Genes (7)