Stochastic model for cell polarity

Cell polarity refers to the spatial asymmetry of molecules on the cell membrane. Altschuler, Angenent, Wang and Wu have proposed a stochastic model for studying the emergence of polarity in the presence of feedback between molecules. We analyze their model further by representing it as a model of an evolving population with interacting individuals. Under a suitable scaling of parameters, we show that in the infinite population limit we get a Fleming--Viot process. Using well-known results for such processes, we establish that cell polarity is exhibited by the model and also study its dependence on the biological parameters of the model.Comment: Published in at http://dx.doi.org/10.1214/11-AAP788 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Quantification of Nematic Cell Polarity in Three-dimensional Tissues

How epithelial cells coordinate their polarity to form functional tissues is an open question in cell biology. Here, we characterize a unique type of polarity found in liver tissue, nematic cell polarity, which is different from vectorial cell polarity in simple, sheet-like epithelia. We propose a conceptual and algorithmic framework to characterize complex patterns of polarity proteins on the surface of a cell in terms of a multipole expansion. To rigorously quantify previously observed tissue-level patterns of nematic cell polarity (Morales-Navarette et al., eLife 8:e44860, 2019), we introduce the concept of co-orientational order parameters, which generalize the known biaxial order parameters of the theory of liquid crystals. Applying these concepts to three-dimensional reconstructions of single cells from high-resolution imaging data of mouse liver tissue, we show that the axes of nematic cell polarity of hepatocytes exhibit local coordination and are aligned with the biaxially anisotropic sinusoidal network for blood transport. Our study characterizes liver tissue as a biological example of a biaxial liquid crystal. The general methodology developed here could be applied to other tissues or in-vitro organoids.Comment: 27 pages, 9 color figure

Editorial overview: Membrane traffic and cell polarity

No abstract available

Ca2+ influx and phosphoinositide signalling are essential for the establishment and maintenance of cell polarity in monospores from the red alga Porphyra yezoensis

The asymmetrical distribution of F-actin directed by cell polarity has been observed during the migration of monospores from the red alga Porphyra yezoensis. The significance of Ca2+ influx and phosphoinositide signalling during the formation of cell polarity in migrating monospores was analysed pharmacologically. The results indicate that the inhibition of the establishment of cell polarity, as judged by the ability of F-actin to localize asymmetrically, cell wall synthesis, and development into germlings, occurred when monospores were treated with inhibitors of the Ca2+ permeable channel, phospholipase C (PLC), diacylglycerol kinase, and inositol-1,4,5-trisphosphate receptor. Moreover, it was also found that light triggered the establishment of cell polarity via photosynthetic activity but not its direction, indicating that the Ca2+ influx and PLC activation required for the establishment of cell polarity are light dependent. By contrast, inhibition of phospholipase D (PLD) prevented the migration of monospores but not the asymmetrical localization of F-actin. Taken together, these findings suggest that there is functional diversity between the PLC and PLD signalling systems in terms of the formation of cell polarity; the former being critical for the light-dependent establishment of cell polarity and the latter playing a role in the maintenance of established cell polarity

Dynamics of cell polarity in tissue morphogenesis: A comparative view from Drosophila and Ciona [version 1; referees: 2 approved]

Citation: Veeman, M. T., & McDonald, J. A. (2016). Dynamics of cell polarity in tissue morphogenesis: A comparative view from Drosophila and Ciona [version 1; referees: 2 approved]. F1000Research, 5. doi:10.12688/F1000RESEARCH.8011.1Tissues in developing embryos exhibit complex and dynamic rearrangements that shape forming organs, limbs, and body axes. Directed migration, mediolateral intercalation, lumen formation, and other rearrangements influence the topology and topography of developing tissues. These collective cell behaviors are distinct phenomena but all involve the fine-grained control of cell polarity. Here we review recent findings in the dynamics of polarized cell behavior in both the Drosophila ovarian border cells and the Ciona notochord. These studies reveal the remarkable reorganization of cell polarity during organ formation and underscore conserved mechanisms of developmental cell polarity including the Par/atypical protein kinase C (aPKC) and planar cell polarity pathways. These two very different model systems demonstrate important commonalities but also key differences in how cell polarity is controlled in tissue morphogenesis. Together, these systems raise important, broader questions on how the developmental control of cell polarity contributes to morphogenesis of diverse tissues across the metazoa. © 2016 Veeman MT and McDonald JA

A mass conserved reaction-diffusion system captures properties of cell polarity

Various molecules exclusively accumulate at the front or back of migrating eukaryotic cells in response to a shallow gradient of extracellular signals. Directional sensing and signal amplification highlight the essential properties in the migrating cells, known as cell polarity. In addition to these, such properties of cell polarity involve unique determination of migrating direction (uniqueness of axis) and localized gradient sensing at the front edge (localization of sensitivity), both of which may be required for smooth migration. Here we provide the mass conservation system based on the reaction-diffusion system with two components, where the mass of the two components is always conserved. Using two models belonging to this mass conservation system, we demonstrate through both numerical simulation and analytical approximations that the spatial pattern with a single peak (uniqueness of axis) can be generally observed and that the existent peak senses a gradient of parameters at the peak position, which guides the movement of the peak. We extended this system with multiple components, and we developed a multiple-component model in which cross-talk between members of the Rho family of small GTPases is involved. This model also exhibits the essential properties of the two models with two components. Thus, the mass conservation system shows properties similar to those of cell polarity, such as uniqueness of axis and localization of sensitivity, in addition to directional sensing and signal amplification.Comment: PDF onl

Epithelial cell polarity: a major gatekeeper against cancer?

The correct establishment and maintenance of cell polarity are crucial for normal cell physiology and tissue homeostasis. Conversely, loss of cell polarity, tissue disorganisation and excessive cell growth are hallmarks of cancer. In this review, we focus on identifying the stages of tumoural development that are affected by the loss or deregulation of epithelial cell polarity. Asymmetric division has recently emerged as a major regulatory mechanism that controls stem cell numbers and differentiation. Links between cell polarity and asymmetric cell division in the context of cancer will be examined. Apical–basal polarity and cell–cell adhesion are tightly interconnected. Hence, how loss of cell polarity in epithelial cells may promote epithelial mesenchymal transition and metastasis will also be discussed. Altogether, we present the argument that loss of epithelial cell polarity may have an important role in both the initiation of tumourigenesis and in later stages of tumour development, favouring the progression of tumours from benign to malignancy

Insights into the molecular mechanism of Sjogren's syndrome

Sjogren’s syndrome (SS) is a chronic autoimmune disease, that affects primarily salivary and lacrimal glands, leading to increased morbidity. Recent studies indicate that loss of salivary gland function is associated with defective cell polarity, lymphocytic infiltration and fibrosis. Our previous studies showed that deregulation of E-cadherin-mediated adhesion was associated with nuclear localization of YAP and suggested that the latter may be a key event in SS. In this study, our goal was to align altered morphological features in SS with cell polarity regulators. Specifically, we focused on the Par complex, known to play an important role in epithelial polarity, as well as components of tight junctions (TJs), ZO-1 and JAM-1, and compared them to changes in their expression and localization with markers of fibrosis, vimentin and α-smooth muscle actin (α-SMA). Using immunofluorescence staining and confocal microscopy we examined expression levels of YAP, Par3, ZO-1, JAM-1, vimentin, and α-SMA, and correlated them with a ductal differentiation marker K7 and a marker for lymphocytic infiltration, CD45+. Our results showed reduced levels of Par3, ZO-1 and JAM-1, in tissues from SS patients that were associated with increased nuclear localization of YAP. Collectively, these studies suggest that cell polarity cues are critical for normal function of salivary glands and that their deregulation is likely to be the underlying basis of at least a subset of SS patients. These findings will further contribute to a better understanding of the molecular basis of SS and will serve in improved diagnosis and future therapeutic intervention