scholarly journals Continuum Theory for Planar Cell Polarity

2021 ◽  
Author(s):  
Mohd. Suhail Rizvi ◽  
Divyoj Singh ◽  
Mohit Kumar Jolly
Keyword(s):  
Cell Membrane ◽  
Cell Polarity ◽  
Protein Interactions ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Continuum Theory ◽  
Fruit Fly ◽  
Tissue Level ◽  
Cellular Protein ◽  
Tube Formation

Planar Cell Polarity (PCP), characterized by asymmetric localization of proteins at the cell membrane within the epithelial plane, plays essential roles in embryonic development and physiological functions. The significance of PCP can be appreciated by the outcomes of PCP failure in the form of defects in neural tube formation, tracheal malfunctions, organ shape misregulation, hair follicle misalignment etc. Extensive experimental works on PCP in fruit fly Drosophila melanogaster have classified the proteins involved in PCP into two modules: 'core' module, acting locally by inter-cellular protein interactions, and, 'global' module, responsible for the alignment of cell polarities with that of the tissue axis. Despite the involvement of different molecular players, the asymmetric localization of the proteins of the two modules on cell membrane primarily involve inter-cellular dimer formations. We have developed a continuum model of the localization of PCP proteins on the cell membrane and its regulation via intra- and inter-cellular protein-protein interactions. We have identified the conditions for the asymmetric protein localization, or PCP establishment, for uniform and graded protein expression levels in the tissue. We have found that in the absence of any tissue level expression gradient the polarized state of the tissue is not stable against finite length perturbations which is also a property of the active polar matter. However, in the presence of tissue level expression gradients of proteins the polarized state remains stable. We have also looked at the influence of the loss of PCP proteins from a select regions of the tissue on the polarization of the cells outside of that region. This continuum theory of the planar cell polarity can be coupled with the active matter hydrodynamics to study the cell flows and their regulation by genetic machinery.

scholarly journals The cell biology of planar cell polarity

2014 ◽  
Vol 207 (2) ◽  
pp. 171-179 ◽  
Author(s):  
Danelle Devenport
Keyword(s):  
Cell Polarity ◽  
Cell Biology ◽  
Planar Cell Polarity ◽  
Protein Transport ◽  
Protein Localization ◽  
Tissue Level ◽  
Mechanical Forces ◽  
Cellular Polarity ◽  
Asymmetric Partitioning ◽  
Local Cell

Planar cell polarity (PCP) refers to the coordinated alignment of cell polarity across the tissue plane. Key to the establishment of PCP is asymmetric partitioning of cortical PCP components and intercellular communication to coordinate polarity between neighboring cells. Recent progress has been made toward understanding how protein transport, endocytosis, and intercellular interactions contribute to asymmetric PCP protein localization. Additionally, the functions of gradients and mechanical forces as global cues that bias PCP orientation are beginning to be elucidated. Together, these findings are shedding light on how global cues integrate with local cell interactions to organize cellular polarity at the tissue level.

scholarly journals Coupling Planar Cell Polarity Signaling to Morphogenesis

2002 ◽  
Vol 2 ◽  
pp. 434-454 ◽  
Author(s):  
Jeffrey D. Axelrod ◽  
Helen McNeill
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Fruit Fly ◽  
Convergent Extension ◽  
Cytoskeletal Reorganization ◽  
Directional Information ◽  
Cochlear Hair Cell ◽  
Cellular Asymmetry ◽  
Pcp Signaling ◽  
Unknown Signal

Epithelial cells and other groups of cells acquire a polarity orthogonal to their apical–basal axes, referred to as Planar Cell Polarity (PCP). The process by which these cells become polarized requires a signaling pathway using Frizzled as a receptor. Responding cells sense cues from their environment that provide directional information, and they translate this information into cellular asymmetry. Most of what is known about PCP derives from studies in the fruit fly,Drosophila. We review what is known about how cells translate an unknown signal into asymmetric cytoskeletal reorganization. We then discuss how the vertebrate processes of convergent extension and cochlear hair-cell development may relate toDrosophilaPCP signaling.

scholarly journals Control of vertebrate core planar cell polarity protein localization and dynamics by Prickle 2

Development ◽  
2015 ◽  
Vol 142 (19) ◽  
pp. 3429-3439 ◽  
Author(s):  
Mitchell T. Butler ◽  
John B. Wallingford
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Protein Localization

scholarly journals Par3 is essential for the establishment of planar cell polarity of inner ear hair cells

2019 ◽  
Vol 116 (11) ◽  
pp. 4999-5008 ◽  
Author(s):  
Andre Landin Malt ◽  
Zachary Dailey ◽  
Julia Holbrook-Rasmussen ◽  
Yuqiong Zheng ◽  
Arielle Hogan ◽  
...  
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Cell Polarity ◽  
Hair Cells ◽  
Planar Cell Polarity ◽  
Tissue Level ◽  
Hair Bundle ◽  
Nucleotide Exchange ◽  
Genetic Mosaic ◽  
Pcp Signaling

In the inner ear sensory epithelia, stereociliary hair bundles atop sensory hair cells are mechanosensory apparatus with planar polarized structure and orientation. This is established during development by the concerted action of tissue-level, intercellular planar cell polarity (PCP) signaling and a hair cell-intrinsic, microtubule-mediated machinery. However, how various polarity signals are integrated during hair bundle morphogenesis is poorly understood. Here, we show that the conserved cell polarity protein Par3 is essential for planar polarization of hair cells. Par3 deletion in the inner ear disrupted cochlear outgrowth, hair bundle orientation, kinocilium positioning, and basal body planar polarity, accompanied by defects in the organization and cortical attachment of hair cell microtubules. Genetic mosaic analysis revealed that Par3 functions both cell-autonomously and cell-nonautonomously to regulate kinocilium positioning and hair bundle orientation. At the tissue level, intercellular PCP signaling regulates the asymmetric localization of Par3, which in turn maintains the asymmetric localization of the core PCP protein Vangl2. Mechanistically, Par3 interacts with and regulates the localization of Tiam1 and Trio, which are guanine nucleotide exchange factors (GEFs) for Rac, thereby stimulating Rac-Pak signaling. Finally, constitutively active Rac1 rescued the PCP defects in Par3-deficient cochleae. Thus, a Par3–GEF–Rac axis mediates both tissue-level and hair cell-intrinsic PCP signaling.

scholarly journals CLAMP/Spef1 regulates planar cell polarity signaling and asymmetric microtubule accumulation in the Xenopus ciliated epithelia

2018 ◽  
Vol 217 (5) ◽  
pp. 1633-1641 ◽  
Author(s):  
Sun K. Kim ◽  
Siwei Zhang ◽  
Michael E. Werner ◽  
Eva J. Brotslaw ◽  
Jennifer W. Mitchell ◽  
...  
Keyword(s):  
Cell Division ◽  
Epithelial Cells ◽  
Cell Signaling ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Apical Cell ◽  
Cell Cortex ◽  
Pcp Signaling ◽  
Cell Cell

Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell–cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity. We have identified CLAMP/Spef1 as a novel regulator of PCP signaling. In addition to decorating microtubules (MTs) and the ciliary rootlet, a pool of CLAMP localizes at the apical cell cortex. Depletion of CLAMP leads to the loss of PCP protein asymmetry, defects in cilia polarity, and defects in the angle of cell division. Additionally, depletion of CLAMP leads to a loss of the atypical cadherin-like molecule Celrs2, suggesting that CLAMP facilitates the stabilization of junctional interactions responsible for proper PCP protein localization. Depletion of CLAMP also affects the polarized organization of MTs. We hypothesize that CLAMP facilitates the establishment of cell polarity and promotes the asymmetric accumulation of MTs downstream of the establishment of proper PCP.

scholarly journals Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Robert J Huebner ◽  
Abdul Naseer Malmi-Kakkada ◽  
Sena Sarikaya ◽  
Shinuo Weng ◽  
D Thirumalai ◽  
...  
Keyword(s):  
Cell Biology ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Tissue Level ◽  
Cell Junctions ◽  
Convergent Extension ◽  
Length Scales ◽  
Mechanical Heterogeneity ◽  
Multiple Length Scales ◽  
Cell Cell

Morphogenesis is governed by the interplay of molecular signals and mechanical forces across multiple length scales. The last decade has seen tremendous advances in our understanding of the dynamics of protein localization and turnover at sub-cellular length scales, and at the other end of the spectrum, of mechanics at tissue-level length scales. Integrating the two remains a challenge, however, because we lack a detailed understanding of the subcellular patterns of mechanical properties of cells within tissues. Here, in the context of the elongating body axis of Xenopus embryos, we combine tools from cell biology and physics to demonstrate that individual cell-cell junctions display finely-patterned local mechanical heterogeneity along their length. We show that such local mechanical patterning is essential for the cell movements of convergent extension and is imparted by locally patterned clustering of a classical cadherin. Finally, the patterning of cadherins and thus local mechanics along cell-cell junctions are controlled by Planar Cell Polarity signaling, a key genetic module for CE that is mutated in diverse human birth defects.

scholarly journals Par3 interacts with Prickle3 to generate apical PCP complexes in the vertebrate neural plate

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ilya Chuykin ◽  
Olga Ossipova ◽  
Sergei Y Sokol
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Tube Formation ◽  
Neural Plate ◽  
Asymmetric Distribution ◽  
Junctional Complexes ◽  
Pcp Complexes ◽  
Apical Localization

Vertebrate neural tube formation depends on the coordinated orientation of cells in the tissue known as planar cell polarity (PCP). In the Xenopus neural plate, PCP is marked by the enrichment of the conserved proteins Prickle3 and Vangl2 at anterior cell boundaries. Here we show that the apical determinant Par3 is also planar polarized in the neuroepithelium, suggesting a role for Par3 in PCP. Consistent with this hypothesis, interference with Par3 activity inhibited asymmetric distribution of PCP junctional complexes and caused neural tube defects. Importantly, Par3 physically associated with Prickle3 and promoted its apical localization, whereas overexpression of a Prickle3-binding Par3 fragment disrupted PCP in the neural plate. We also adapted proximity biotinylation assay for use in Xenopus embryos and show that Par3 functions by enhancing the formation of the anterior apical PCP complex. These findings describe a mechanistic link between the apical localization of PCP components and morphogenetic movements underlying neurulation.

scholarly journals Planar cell polarity induces local microtubule bundling for coordinated ciliary beating

2021 ◽  
Vol 220 (7) ◽  
Author(s):  
Shogo Nakayama ◽  
Tomoki Yano ◽  
Toshinori Namba ◽  
Satoshi Konishi ◽  
Maki Takagishi ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Single Molecule ◽  
Molecular Basis ◽  
Planar Cell Polarity ◽  
Tissue Level ◽  
Junctional Complex ◽  
Ciliary Beating ◽  
Voltage Electron ◽  
Apical Junctional Complex

Multiciliated cells (MCCs) in tracheas generate mucociliary clearance through coordinated ciliary beating. Apical microtubules (MTs) play a crucial role in this process by organizing the planar cell polarity (PCP)–dependent orientation of ciliary basal bodies (BBs), for which the underlying molecular basis remains elusive. Herein, we found that the deficiency of Daple, a dishevelled-associating protein, in tracheal MCCs impaired the planar polarized apical MTs without affecting the core PCP proteins, causing significant defects in the BB orientation at the cell level but not the tissue level. Using live-cell imaging and ultra-high voltage electron microscope tomography, we found that the apical MTs accumulated and were stabilized by side-by-side association with one side of the apical junctional complex, to which Daple was localized. In vitro binding and single-molecule imaging revealed that Daple directly bound to, bundled, and stabilized MTs through its dimerization. These features convey a PCP-related molecular basis for the polarization of apical MTs, which coordinate ciliary beating in tracheal MCCs.

scholarly journals Par3 regulates Rac1 signaling and microtubule organization during planar polarization of auditory hair cells

2018 ◽  
Author(s):  
Andre Landin Malt ◽  
Zachary Dailey ◽  
Julia Holbrook-rasmussen ◽  
Yuqiong Zheng ◽  
Quansheng Du ◽  
...  
Keyword(s):  
Inner Ear ◽  
Cell Polarity ◽  
Hair Cells ◽  
Planar Cell Polarity ◽  
Tissue Level ◽  
Hair Bundle ◽  
Microtubule Organization ◽  
Reciprocal Regulation ◽  
Auditory Hair Cells ◽  
Pcp Signaling

AbstractIn the inner ear sensory epithelia, hair bundles atop sensory hair cells are mechanosensory apparati with planar polarized structure and orientation. This is established during development by the concerted action of tissue-level planar cell polarity (PCP) signaling and a hair cell-intrinsic, microtubule-mediated machinery. However, how various polarity signals are integrated during hair bundle morphogenesis is poorly understood. Here, we show that the conserved cell polarity protein Par3 plays a key role in planar polarization of hair cells. Par3 deletion in the inner ear resulted in defects in cochlear length, hair bundle orientation and kinocilium positioning. During PCP establishment, Par3 promotes localized Rac-Pak signaling through an interaction with Tiam1. Par3 regulates microtubule dynamics and organization, which is crucial for basal body positioning. Moreover, there is reciprocal regulation of Par3 and the core PCP molecule Vangl2. Thus, we conclude that Par3 is an effector and integrator of cell-intrinsic and tissue-level PCP signaling.One sentence summaryPar3 regulates planar polarity of auditory hair cells

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