Emergence of planar cell polarity from the interplay of asymmetric interaction and tissue-level gradients

Abstract

AbstractPlanar cell polarity (PCP) – asymmetric localization of proteins at cell-cell interface – is essential for embryonic development and physiological functions. Abnormalities in PCP can lead to neural tube closure defects, misalignment in hair follicles etc. Thus, decoding the mechanism responsible for PCP establishment and maintenance remains an open fundamental question. While various molecules – broadly classified into “global” and “local” modules – have been well investigated, their necessity and sufficiency in explaining PCP and connecting their perturbations and defects in experimentally observed patterns has not been examined. Here, we develop a minimal model that captures the proposed features of these two modules- a global tissue level gradient and local asymmetric distribution of protein complexes. Our model results suggest that while polarity can emerge in absence of a gradient, the gradient can provide the direction of polarity as well as offer robustness for maintenance of PCP in presence of stochastic perturbations. We also recapitulated swirling patterns (seen experimentally) and the features of non-domineering autonomy, using only three free parameters in the model - protein binding rate, concentration of proteins forming heterodimer across cell boundaries and steepness of gradient. Our results explain how self-stabilizing asymmetric localisations in presence of tissue-level gradient can lead to robust PCP patterns in diverse biological systems and reveals the minimal design principles for a polarized system.