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

2020 ◽  
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

AbstractMorphogenesis 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 a vertebrate embryo, 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 Planar cell polarity: moving from single cells to tissue-scale biology

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev186346
Author(s):  
Marek Mlodzik
Keyword(s):  
Cell Polarity ◽  
Cell Biology ◽  
Planar Cell Polarity ◽  
Single Cells ◽  
Field Studies ◽  
Model System ◽  
Convergent Extension ◽  
Organ Function ◽  
Biophysical Studies ◽  
Cell Positioning

ABSTRACTPlanar cell polarity (PCP) reflects cellular orientation within the plane of an epithelium. PCP is crucial during many biological patterning processes and for organ function. It is omnipresent, from convergent-extension mechanisms during early development through to terminal organogenesis, and it regulates many aspects of cell positioning and orientation during tissue morphogenesis, organ development and homeostasis. Suzanne Eaton used the power of Drosophila as a model system to study PCP, but her vision of, and impact on, PCP studies in flies translates to all animal models. As I highlight here, Suzanne's incorporation of quantitative biophysical studies of whole tissues, integrated with the detailed cell biology of PCP phenomena, completely changed how the field studies this intriguing feature. Moreover, Suzanne's impact on ongoing and future PCP studies is fundamental, long-lasting and transformative.

scholarly journals Planar Cell Polarity Defects and Hearing Loss in Sperm-Associated Antigen 6 (Spag6)-Deficient Mice

2020 ◽  
Author(s):  
Xiaofei Li ◽  
Daogong Zhang ◽  
Lei Xu ◽  
Yuechen Han ◽  
Wenwen Liu ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Structural Features ◽  
Sensory Cells ◽  
Basal Bodies ◽  
Cellular Polarity ◽  
Central Apparatus ◽  
Deficient Mice

Spag6 encodes an axoneme central apparatus protein that is required for normal flagellar and cilia motility. Recent findings suggest that Spag6 also plays a role in ciliogenesis, orientation of cilia basal feet, and planar polarity. Sensory cells of the inner ear display unique structural features that underlie their mechanosensitivity. They represent a distinctive form of cellular polarity, known as planar cell polarity (PCP). However, a role for Spag6 in the inner ear has not yet been explored. In the present study, the function of Spag6 in the inner ear was examined using Spag6-deficient mice. Our results demonstrate hearing loss in the Spag6 mutants, associated with abnormalities in cellular patterning, cell shape, stereocilia bundles and basal bodies, as well as abnormally distributed Frizzled class receptor 6 (FZD6), suggesting that Spag6 participates in PCP regulation. Moreover, we found that the sub-apical microtubule meshwork was disrupted. Our observations suggest new functions for Spag6 in hearing and PCP in the inner ear.

scholarly journals Ancestral roles of atypical cadherins in planar cell polarity

2020 ◽  
Vol 117 (32) ◽  
pp. 19310-19320
Author(s):  
Maria Brooun ◽  
Alexander Klimovich ◽  
Mikhail Bashkurov ◽  
Bret J. Pearson ◽  
Robert E. Steele ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Sister Group ◽  
The Body ◽  
Cell Alignment ◽  
Actin Organization ◽  
Tissue Organization ◽  
Ancestral Function ◽  
Local Cell

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins inHydra, a member of phylum Cnidaria a sister group of bilaterian. We foundHydradoes not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral–aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell–cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization.

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 P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

2016 ◽  
Vol 212 (2) ◽  
pp. 199-217 ◽  
Author(s):  
Cédric Plutoni ◽  
Elsa Bazellieres ◽  
Maïlys Le Borgne-Rochet ◽  
Franck Comunale ◽  
Agusti Brugues ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Cell Biology ◽  
Cell Polarization ◽  
Collective Cell Migration ◽  
Mechanical Forces ◽  
Tumor Aggressiveness ◽  
And Migration ◽  
Cell Cell

Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.

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 Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear

2019 ◽  
Vol 30 (18) ◽  
pp. 2422-2434 ◽  
Author(s):  
Cristy Tower-Gilchrist ◽  
Stephanie A. Zlatic ◽  
Dehong Yu ◽  
Qing Chang ◽  
Hao Wu ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Adaptor Protein ◽  
Rab Proteins ◽  
Convergent Extension ◽  
Cellular Polarity ◽  
Profound Hearing Loss ◽  
Recycling Endosomes ◽  
Axis Parallel ◽  
Rna Knockdown

Planar cell polarity (PCP) regulates coordinated cellular polarity among neighboring cells to establish a polarity axis parallel to the plane of the tissue. Disruption in PCP results in a range of developmental anomalies and diseases. A key feature of PCP is the polarized and asymmetric localization of several membrane PCP proteins, which is essential to establish the polarity axis to orient cells coordinately. However, the machinery that regulates the asymmetric partition of PCP proteins remains largely unknown. In the present study, we show Van gogh-like 2 (Vangl2) in early and recycling endosomes as made evident by colocalization with diverse endosomal Rab proteins. Vangl2 biochemically interacts with adaptor protein-3 complex (AP-3). Using short hairpin RNA knockdown, we found that Vangl2 subcellular localization was modified in AP-3–depleted cells. Moreover, Vangl2 membrane localization within the cochlea is greatly reduced in AP-3–deficient mocha mice, which exhibit profound hearing loss. In inner ears from AP-3–deficient mocha mice, we observed PCP-dependent phenotypes, such as misorientation and deformation of hair cell stereociliary bundles and disorganization of hair cells characteristic of defects in convergent extension that is driven by PCP. These findings demonstrate a novel role of AP-3–mediated sorting mechanisms in regulating PCP proteins.

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