The Wnt Coreceptor Ryk Regulates Wnt/Planar Cell Polarity by Modulating the Degradation of the Core Planar Cell Polarity Component Vangl2

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.

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The Drosophila RNA binding protein Nab2 patterns dendritic arbors and axons via the planar cell polarity pathway

10.1101/2021.11.10.468151 ◽

2021 ◽

Author(s):

Kenneth H. Moberg ◽

Edwin B. Corgiat ◽

Sara List ◽

J. Christopher Rounds ◽

Dehong Yu ◽

...

Keyword(s):

Cell Polarity ◽

Planar Cell Polarity ◽

Rna Binding ◽

Rna Binding Proteins ◽

Axon Growth ◽

Planar Cell Polarity Pathway ◽

Translational Repressor ◽

The Core ◽

Dendritic Arbors ◽

Axon Projection

RNA binding proteins support neurodevelopment by modulating numerous steps in post-transcriptional regulation, including splicing, export, translation, and turnover of mRNAs that can traffic into axons and dendrites. One such RBP is ZC3H14, which is lost in an inherited intellectual disability. The Drosophila melanogaster ZC3H14 ortholog, Nab2, localizes to neuronal nuclei and cytoplasmic ribonucleoprotein granules, and is required for olfactory memory and proper axon projection into brain mushroom bodies. Nab2 can act as a translational repressor in conjunction with the Fragile-X mental retardation protein homolog Fmr1 and shares target RNAs with the Fmr1-interacting RBP Ataxin-2. However, neuronal signaling pathways regulated by Nab2 and their potential roles outside of mushroom body axons remain undefined. Here, we demonstrate that Nab2 restricts branching and projection of larval sensory dendrites via the planar cell polarity pathway, and that this link may provide a conserved mechanism through which Nab2/ZC3H14 modulates projection of both axons and dendrites. Planar cell polarity proteins are enriched in a Nab2-regulated brain proteomic dataset. Complementary genetic data indicate that Nab2 guides dendrite and axon growth through the planar-cell-polarity pathway. Analysis of the core planar cell polarity protein Vang, which is depleted in the Nab2 mutant whole-brain proteome, uncovers selective and dramatic loss of Vang within axon/dendrite-enriched brain neuropil relative to brain regions containing cell bodies. Collectively, these data demonstrate that Nab2 regulates dendritic arbors and axon projection by a planar-cell-polarity-linked mechanism and identify Nab2 as required for accumulation of the core planar cell polarity factor Vang in distal neuronal projections.

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Planar cell polarity: the prickle gene acts independently on both the Ds/Ft and the Stan Systems

10.1101/212167 ◽

2017 ◽

Author(s):

José Casal ◽

Beatriz Ibáñez-Jiménez ◽

Peter A. Lawrence

Keyword(s):

Cell Polarity ◽

Planar Cell Polarity ◽

The Body ◽

Functional Link ◽

Molecular Systems ◽

The Core ◽

Core Proteins ◽

Principal Axes ◽

Essential Components ◽

Two Systems

ABSTRACTEpithelial cells are polarised within the plane of the epithelium, forming oriented structures whose coordinated and consistent polarity (planar cell polarity, PCP) relates to the principal axes of the body or organ. In Drosophila at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the “core” or Stan system. Here we study the prickle gene and its protein products Prickle and Spiny leg. Much research on PCP has focused on the asymmetric localisation of core proteins in the cell and as a result prickle was placed in the heart of the Stan system. Here we ask if this view is correct and how the prickle gene relates to the two systems. We find that prickle can affect, separately, both systems — however, neither Pk nor Sple are essential components of the Ds/Ft or the Stan system, nor do they act as a functional link between the two systems.

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Meru couples planar cell polarity with apical-basal polarity during asymmetric cell division

eLife ◽

10.7554/elife.25014 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 7

Author(s):

Jennifer J Banerjee ◽

Birgit L Aerne ◽

Maxine V Holder ◽

Simon Hauri ◽

Matthias Gstaiger ◽

...

Keyword(s):

Cell Polarity ◽

Planar Cell Polarity ◽

Asymmetric Cell Division ◽

Building Blocks ◽

Posterior Cortex ◽

Daughter Cells ◽

The Core ◽

Cell Tissue ◽

Specific Factors ◽

Polarity Factor

Polarity is a shared feature of most cells. In epithelia, apical-basal polarity often coexists, and sometimes intersects with planar cell polarity (PCP), which orients cells in the epithelial plane. From a limited set of core building blocks (e.g. the Par complexes for apical-basal polarity and the Frizzled/Dishevelled complex for PCP), a diverse array of polarized cells and tissues are generated. This suggests the existence of little-studied tissue-specific factors that rewire the core polarity modules to the appropriate conformation. In Drosophila sensory organ precursors (SOPs), the core PCP components initiate the planar polarization of apical-basal determinants, ensuring asymmetric division into daughter cells of different fates. We show that Meru, a RASSF9/RASSF10 homologue, is expressed specifically in SOPs, recruited to the posterior cortex by Frizzled/Dishevelled, and in turn polarizes the apical-basal polarity factor Bazooka (Par3). Thus, Meru belongs to a class of proteins that act cell/tissue-specifically to remodel the core polarity machinery.

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Shaping the nervous system: role of the core planar cell polarity genes

Nature Reviews Neuroscience ◽

10.1038/nrn3525 ◽

2013 ◽

Vol 14 (8) ◽

pp. 525-535 ◽

Cited By ~ 80

Author(s):

Fadel Tissir ◽

André M. Goffinet

Keyword(s):

Nervous System ◽

Cell Polarity ◽

Planar Cell Polarity ◽

The Core

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Microtubules provide directional information for core PCP function

eLife ◽

10.7554/elife.02893 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 72

Author(s):

Maja Matis ◽

David A Russler-Germain ◽

Qie Hu ◽

Claire J Tomlin ◽

Jeffrey D Axelrod

Keyword(s):

Mathematical Simulation ◽

Cell Polarity ◽

Planar Cell Polarity ◽

Global Alignment ◽

Directional Information ◽

The Core ◽

Initial Polarization ◽

Core Module ◽

Pcp Signaling ◽

Apical Junctions

Planar cell polarity (PCP) signaling controls the polarization of cells within the plane of an epithelium. Two molecular modules composed of Fat(Ft)/Dachsous(Ds)/Four-jointed(Fj) and a ‘PCP-core’ including Frizzled(Fz) and Dishevelled(Dsh) contribute to polarization of individual cells. How polarity is globally coordinated with tissue axes is unresolved. Consistent with previous results, we find that the Ft/Ds/Fj-module has an effect on a MT-cytoskeleton. Here, we provide evidence for the model that the Ft/Ds/Fj-module provides directional information to the core-module through this MT organizing function. We show Ft/Ds/Fj-dependent initial polarization of the apical MT-cytoskeleton prior to global alignment of the core-module, reveal that the anchoring of apical non-centrosomal MTs at apical junctions is polarized, observe that directional trafficking of vesicles containing Dsh depends on Ft, and demonstrate the feasibility of this model by mathematical simulation. Together, these results support the hypothesis that Ft/Ds/Fj provides a signal to orient core PCP function via MT polarization.

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Wnt ligands are not required for planar cell polarity in the Drosophila wing or notum

10.1101/2020.06.05.137182 ◽

2020 ◽

Author(s):

Ben Ewen-Campen ◽

Typhaine Comyn ◽

Eric Vogt ◽

Norbert Perrimon

Keyword(s):

Cell Polarity ◽

Planar Cell Polarity ◽

Wnt Signaling Pathway ◽

Loss Of Function ◽

Knock Out ◽

The Core ◽

Drosophila Wing ◽

Wnt Ligands ◽

Pcp Signaling ◽

Dual Functions

AbstractThe frizzled (fz) and disheveled (dsh) genes are highly conserved members of the core planar cell polarity (PCP) pathway and of the Wnt signaling pathway. Given these dual functions, a number of studies have examined whether Wnt ligands may provide a global, tissue-scale orientation cue for PCP establishment during development, and these studies have reached differing conclusions. In this study, we re-examine this issue in the Drosophila melanogaster wing and notum using split-Gal4 co-expression analysis, systematic pairwise and triple somatic CRISPR-based knock-outs and double RNAi experiments. Pairwise loss-of-function experiments targeting wg together with other Wnt genes does not produce PCP defects, neither via somatic CRISPR nor RNAi. In addition, somatic knock-out of evi (aka wntless), which is required for the secretion of all Wnt ligands expressed in these tissues, did not produce detectable PCP phenotypes. Altogether, we were unable to find support for the hypothesis that Wnt ligands contribute to PCP signaling in the Drosophila wing or notum.

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Dishevelled stabilization by the ciliopathy protein Rpgrip1l is essential for planar cell polarity

The Journal of Cell Biology ◽

10.1083/jcb.201111009 ◽

2012 ◽

Vol 198 (5) ◽

pp. 927-940 ◽

Cited By ~ 48

Author(s):

Alexia Mahuzier ◽

Helori-Mael Gaudé ◽

Valentina Grampa ◽

Isabelle Anselme ◽

Flora Silbermann ◽

...

Keyword(s):

Cell Polarity ◽

Planar Cell Polarity ◽

Molecular Mechanisms ◽

Cultured Cells ◽

Floor Plate ◽

Renal Cells ◽

Polarization Process ◽

Planar Polarity ◽

The Core ◽

Cellular Events

Cilia are at the core of planar polarity cellular events in many systems. However, the molecular mechanisms by which they influence the polarization process are unclear. Here, we identify the function of the ciliopathy protein Rpgrip1l in planar polarity. In the mouse cochlea and in the zebrafish floor plate, Rpgrip1l was required for positioning the basal body along the planar polarity axis. Rpgrip1l was also essential for stabilizing dishevelled at the cilium base in the zebrafish floor plate and in mammalian renal cells. In rescue experiments, we showed that in the zebrafish floor plate the function of Rpgrip1l in planar polarity was mediated by dishevelled stabilization. In cultured cells, Rpgrip1l participated in a complex with inversin and nephrocystin-4, two ciliopathy proteins known to target dishevelled to the proteasome, and, in this complex, Rpgrip1l prevented dishevelled degradation. We thus uncover a ciliopathy protein complex that finely tunes dishevelled levels, thereby modulating planar cell polarity processes.

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Multi-scale coordination of planar cell polarity in planarians

10.1101/324822 ◽

2018 ◽

Cited By ~ 1

Author(s):

Hanh Thi-Kim Vu ◽

Sarah Mansour ◽

Michael Kücken ◽

Corinna Blasse ◽

Cyril Basquin ◽

...

Keyword(s):

Cell Polarity ◽

Planar Cell Polarity ◽

Design Principle ◽

Cellular Level ◽

The Body ◽

Planar Polarity ◽

Multi Scale ◽

The Core ◽

Evolutionarily Conserved ◽

Polarity Field

SummaryPolarity is a universal design principle of biological systems that manifests at all organizational scales. Although well understood at the cellular level, the mechanisms that coordinate polarity at the tissue or organismal scale remain poorly understood. Here, we make use of the extreme body plan plasticity of planarian flatworms to probe the multi-scale coordination of polarity. Quantitative analysis of ciliary rootlet orientation in the epidermis reveals a global polarization field with head and tail as independent mediators of anteroposterior (A/P) polarization and the body margin influencing mediolateral (M/L) polarization. Mathematical modeling demonstrates that superposition of separate A/P- and M/L-fields can explain the global polarity field and we identify the core planar cell polarity (PCP) and Ft/Ds pathways as their specific mediators. Overall, our study establishes a mechanistic framework for the multi-scale coordination of planar polarity in planarians and establishes the core PCP and Ft/Ds pathways as evolutionarily conserved 2D-polarization module.

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