scholarly journals Frizzled3 inhibits Vangl2-Prickle3 association to establish planar cell polarity in the vertebrate neural plate

2021 ◽  
Author(s):  
Ilya Chuykin ◽  
Keiji Itoh ◽  
Kyeongmi Kim ◽  
Sergei Y. Sokol
Keyword(s):  
Epithelial Cells ◽  
Complex Formation ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Protein Complexes ◽  
Neural Plate ◽  
Van Gogh

The orientation of epithelial cells in the plane of the tissue, known as planar cell polarity (PCP), is regulated by interactions of asymmetrically localized PCP protein complexes. In the Xenopus neural plate, Van Gogh-like2 (Vangl2) and Prickle3 (Pk3) proteins form a complex at the anterior cell boundaries, but how this complex is regulated in vivo remains largely unknown. Here we use proximity biotinylation and crosslinking approaches to show that Vangl2-Pk3 association is inhibited by Frizzled3 (Fz3), a core PCP protein that is specifically expressed in the neuroectoderm and is essential for the establishment of PCP in this tissue. This inhibition required Fz3-dependent Vangl2 phosphorylaton. Consistent with our observations, the complex of Pk3 with nonphosphorylatable Vangl2 did not polarize in the neural plate. These findings provide evidence for in vivo regulation of Vangl2-Pk3 complex formation and localization by a Frizzled receptor.

scholarly journals Frizzled3 inhibits Vangl2-Prickle3 association to establish planar cell polarity in the vertebrate neural plate

2021 ◽  
Author(s):  
Ilya Chuykin ◽  
Kyeongmi Kim ◽  
Sergei Sokol
Keyword(s):  
Epithelial Cells ◽  
Complex Formation ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Protein Complexes ◽  
Neural Plate ◽  
Van Gogh

The orientation of epithelial cells in the plane of the tissue, known as planar cell polarity (PCP), is regulated by interactions of asymmetrically localized PCP protein complexes. In the Xenopus neural plate, Van Gogh-like2 (Vangl2) and Prickle3 (Pk3) proteins form a complex at the anterior cell boundaries, but how this complex is regulated in vivo remains largely unknown. Here we show that Vangl2-Pk3 association is inhibited by Frizzled3 (Fz3), a core PCP protein that is specifically expressed in the neuroectoderm and is essential for the establishment of PCP in this tissue. Proximity biotinylation and crosslinking studies revealed that the Vangl2-Pk3 interaction is suppressed by overexpressed Fz3, but enhanced in Fz3 morphants. In addition, Fz3 induced Vangl2 phosphorylation on T76 and T78, and this phosphorylation was required for Fz3-mediated inhibition of Vangl2-Pk3 complex formation. Consistent with this observation, the complex of Pk3 with nonphosphorylatable Vangl2 was not polarized in the neural plate. These findings provide evidence for in vivo regulation of Vangl2-Pk3 complex formation and localization by a Frizzled receptor.

scholarly journals The core planar cell polarity gene, Vangl2 , directs adult corneal epithelial cell alignment and migration

2016 ◽  
Vol 3 (10) ◽  
pp. 160658 ◽  
Author(s):  
Amy S. Findlay ◽  
D. Alessio Panzica ◽  
Petr Walczysko ◽  
Amy B. Holt ◽  
Deborah J. Henderson ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Cell Polarity ◽  
Corneal Epithelium ◽  
Planar Cell Polarity ◽  
Corneal Epithelial Cell ◽  
Corneal Epithelial Cells ◽  
Corneal Epithelial ◽  
The Core

This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro . Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed. It was shown that signalling through PCP mediators, dishevelled, dishevelled-associated activator of morphogenesis and Rho-associated protein kinase directs the alignment of HCE cells by affecting cytoskeletal reorganization. Cells in which VANGL2 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which Vangl2 had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of Vangl2 in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration in vivo from the periphery (limbus) to the centre of the cornea. Corneal opacity owing to chronic wounding is a major cause of degenerative blindness across the world, and this study shows that Vangl2 activity is required for directional corneal epithelial migration.

scholarly journals New mouse models for high resolution and live imaging of planar cell polarity proteins in vivo

Development ◽  
2021 ◽  
Author(s):  
Lena P. Basta ◽  
Michael Hill-Oliva ◽  
Sarah V. Paramore ◽  
Rishabh Sharan ◽  
Audrey Goh ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Mouse Models ◽  
Planar Cell Polarity ◽  
Protein Complexes ◽  
Protein Localization ◽  
Super Resolution ◽  
Live Imaging ◽  
Cell Junctions ◽  
And Function

The collective polarization of cellular structures and behaviors across a tissue plane is a near universal feature of epithelia known as planar cell polarity (PCP). This property is controlled by the core PCP pathway, which is comprised of highly conserved membrane-associated protein complexes that localize asymmetrically at cell junctions. Here we introduce three new mouse models for investigating the localization and dynamics of transmembrane PCP proteins Celsr1, Fz6, and Vangl2. Using the skin epidermis as a model, we characterize and verify the expression, localization and function of endogenously-tagged Celsr1-3xGFP, Fz6-3xGFP and tdTomato-Vangl2 fusion proteins. Live imaging of Fz6-3xGFP in basal epidermal progenitors reveals that the polarity of the tissue is not fixed through time. Rather asymmetry dynamically shifts during cell rearrangements and divisions, while global, average polarity of the tissue is preserved. We show using super-resolution STED imaging that Fz6-3xGFP and tdTomato-Vangl2 can be resolved, enabling us to observe their complex localization along junctions. We further explore PCP fusion protein localization in the trachea and neural tube, and discover new patterns of PCP expression and localization throughout the mouse embryo.

scholarly journals Myosin Id is required for planar cell polarity in ciliated tracheal and ependymal epithelial cells

Cytoskeleton ◽  
2015 ◽  
Vol 72 (10) ◽  
pp. 503-516 ◽  
Author(s):  
Peter S. Hegan ◽  
Eric Ostertag ◽  
Aron M. Geurts ◽  
Mark S. Mooseker
Keyword(s):  
Epithelial Cells ◽  
Cell Polarity ◽  
Planar Cell Polarity

scholarly journals New genomic data and analyses challenge the traditional vision of animal epithelium evolution

2017 ◽  
Author(s):  
Hassiba Belahbib ◽  
Emmanuelle Renard ◽  
Sébastien Santini ◽  
Cyril Jourda ◽  
Jean-Michel Claverie ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Polarity ◽  
Protein Complexes ◽  
Genomic Data ◽  
Genes Encoding ◽  
Interaction Domains ◽  
Unexpected Findings ◽  
Crumbs Complex ◽  
Adhesive Type ◽  
E Cadherin

AbstractThe emergence of epithelia was the foundation of metazoan expansion. To investigate the early evolution of animal epithelia, we sequenced the genome and transcriptomes of two new sponge species to characterize epithelial markers such as the E-cadherin complex and the polarity complexes for all classes (Calcarea, Demospongiae, Hexactinellida, Homoscleromorpha) of sponges (phylum Porifera) and compare them with their homologs in Placozoa and in Ctenophora. We found that Placozoa and most sponges possess orthologs of all essential genes encoding proteins characteristic of bilaterian epithelial cells, as well as their conserved interaction domains. In stark contrast, we found that ctenophores lack several major polarity complex components such as the Crumbs complex and Scribble. Furthermore, the E-cadherin ctenophore ortholog exhibits a divergent cytoplasmic domain making it unlikely to interact with its canonical cytoplasmic partners. These unexpected findings challenge the current evolutionary paradigm on the emergence of epithelia.SIGNIFICANT STATEMENTEpithelial tissues are a hallmark of metazoans deeply linked to the evolution of the complex morphogenesis processes characterizing their development. However, studies on the epithelial features of non-bilaterians are still sparse and it remains unclear whether the last common metazoan ancestor possessed a fully functional epithelial toolkit or if it was acquired later during metazoan evolution. In this work, we demonstrate that if sponges have a well conserved and functionally predicted epithelial toolkit, Ctenophores have either divergent adhesion complexes or lack essential polarity complexes. Altogether, our results raise a doubt on the homology of protein complexes and structures involved in cell polarity and adhesive type junctions between Ctenophora and Bilateria epithelia.

scholarly journals Tissue fluidity mediated by adherens junction dynamics promotes planar cell polarity-driven ommatidial rotation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nabila Founounou ◽  
Reza Farhadifar ◽  
Giovanna M. Collu ◽  
Ursula Weber ◽  
Michael J. Shelley ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Adherens Junction ◽  
Live Imaging ◽  
Cellular Migration ◽  
Imaging Analysis ◽  
Ommatidial Rotation ◽  
Eye Morphogenesis

AbstractThe phenomenon of tissue fluidity—cells’ ability to rearrange relative to each other in confluent tissues—has been linked to several morphogenetic processes and diseases, yet few molecular regulators of tissue fluidity are known. Ommatidial rotation (OR), directed by planar cell polarity signaling, occurs during Drosophila eye morphogenesis and shares many features with polarized cellular migration in vertebrates. We utilize in vivo live imaging analysis tools to quantify dynamic cellular morphologies during OR, revealing that OR is driven autonomously by ommatidial cell clusters rotating in successive pulses within a permissive substrate. Through analysis of a rotation-specific nemo mutant, we demonstrate that precise regulation of junctional E-cadherin levels is critical for modulating the mechanical properties of the tissue to allow rotation to progress. Our study defines Nemo as a molecular tool to induce a transition from solid-like tissues to more viscoelastic tissues broadening our molecular understanding of tissue fluidity.

scholarly journals Apical restriction of the planar cell polarity component VANGL in pancreatic ducts is required to maintain epithelial integrity

2019 ◽  
Author(s):  
Lydie Flasse ◽  
Siham Yennek ◽  
Cédric Cortijo ◽  
Irene Seijo Barandiaran ◽  
Marine R-C Kraus ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Transmembrane Protein ◽  
Pancreatic Ducts ◽  
Apical Surface ◽  
Epithelial Integrity ◽  
Ductal Cells ◽  
And Function ◽  
Rock Activity

ABSTRACTCell polarity is essential for the architecture and function of numerous epithelial tissues. Here we show how planar cell polarity (PCP), so far studied principally in flat epithelia, is deployed during the morphogenesis of a tubular organ. Using the mammalian pancreas as a model, we report that components of the core PCP pathway such as the transmembrane protein Van Gogh-like (VANGL), are progressively apically-restricted. VANGL expression becomes asymmetrically localized at the apical surface of ductal cells, revealing a planar polarization of the pancreatic duct. We further show that restricting VANGL to these discrete sites of expression is crucial for epithelial integrity. Expansion of expression on basolateral membranes of the progenitors leads to their death and extrusion from the epithelium, as previously observed for perturbations of apico-basal polarity. Using organoids and in vivo analyses, we show that cell elimination is induced by a decrease of Rock activity via Dishevelled.

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