The planar cell polarity Vangl2 protein: From genetics to cellular and molecular functions

Bailly, Éric; Walton, Alexandra; Borg, Jean-Paul

doi:10.1016/j.semcdb.2017.10.030

Cited by 46 publications

(38 citation statements)

References 89 publications

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“…Though the importance of asymmetric expression of PCP proteins in the plane is well established in both Drosophila 22 and vertebrates 23 , little is known regarding their apical restriction. To test the significance of VANGL2 expression and localization, we generated transgenic mouse lines in which Cre-mediated recombination inactivates β-actin promoter-driven GFP expression and induces expression of a Cherry-VANGL2 fusion protein (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…VANGL physically interacts with the majority of the other PCP components 23 and, depending on the context, manipulation of VANGL expression can affect the level and/or the localization of these proteins. Hence, we systematically examined the expression pattern of VANGL2 partners possibly involved in the downregulation of actomyosin contractility.…”

Section: Resultsmentioning

confidence: 99%

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

Flasse

Yennek

Cortijo

et al. 2019

Preprint

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15Cell polarity is essential for the architecture and function of numerous epithelial tissues. Here we show 16 how planar cell polarity (PCP), so far studied principally in flat epithelia, is deployed during the 17 morphogenesis of a tubular organ. Using the mammalian pancreas as a model, we report that 18 components of the core PCP pathway such as the transmembrane protein Van Gogh-like (VANGL), are 19 progressively apically-restricted. VANGL expression becomes asymmetrically localized at the apical 20 surface of ductal cells, revealing a planar polarization of the pancreatic duct. We further show that 21 restricting VANGL to these discrete sites of expression is crucial for epithelial integrity. Expansion of 22 expression on basolateral membranes of the progenitors leads to their death and extrusion from the 23 epithelium, as previously observed for perturbations of apico-basal polarity. Using organoids and in vivo 24 analyses, we show that cell elimination is induced by a decrease of Rock activity via Dishevelled. 25 2 group of six families of proteins is required to coordinate planar polarization between neighboring cells: 38 the transmembrane proteins Frizzled (vertebrate: FZD; fly: FZ), CELSR (CELSR; FMI) and Van Gogh-like 39 (VANGL; STBM/VANG) and the cytosolic-submembrane proteins Dishevelled (DVL; DSH), 40Inversin/Diversin (INV/ANKRD6; DGO), and Prickle (PK). The PCP signaling system employs intra-and inter-41 cellular feedback interactions between its core components to establish their characteristic asymmetric 42 cellular distributions. In the most comprehensively-characterized system, the Drosophila wing blade, the 43 FZ-DSH-DGO complex localizes to intercellular junctions facing the VANG-PK complex in the adjacent 44 cell. FMI, an atypical cadherin, localizes to both sides of the apical junction and bridges the FZ and VANG 45 complexes between neighboring cells. These intercellular interactions are counterbalanced 46 intracellularly by reciprocal inhibitory interactions between the two complexes 1,2 . 47While traditionally depicted in flat epithelia that require directional motion or an oriented structure, it is less 48 clear how these proteins are organized or function in complex epithelia forming tubular structures 3 . The 49 developing pancreas consists of a network of tubes lined by polarized progenitors, the apical membranes of 50 which line the duct lumen 4,5 . This network is dynamic and remodeled throughout development while the 51 pancreatic epithelium grows and progenitors commit to various specialized fates 6 . At embryonic day 52 E10.5, multipotent progenitors are organized around discrete micro-lumens 7,8 . By E12.5, these micro-53 lumens have fused to form a mesh of interconnected ducts. Distal "Tip" progenitors committed to an 54 exocrine fate are restricted to the periphery while the core of this plexus contains bipotent "Trunk" 55 progenitors that subsequently either remain in the epithelium to form mature duct cells or delaminate 56 to give rise to endocrine cells. By birth, the duc...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Flasse

Yennek

Cortijo

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…It works in concert with prickle to modulate PCP polarity in flies, rodents and humans. Vangl2 exerts its regulatory effects by modulating effects on the actin-based cytoskeleton, particularly involved in the embryo implantation and embryogenesis during development, and also PCP orientation of different tissues and/or organs in adult animals such as stereociliary bundles in the cochlea of the inner ear in rodents and humans [36–38]. Indeed, Vangl2 (and also Vangl1) are expressed by Sertoli and germ cells in the testis [10].…”

Section: The Vangl2 (Van Gogh-like 2) Modelmentioning

confidence: 99%

Regulation of spermatid polarity by the actin- and microtubule (MT)-based cytoskeletons

Li¹,

Mao²,

Wu³

et al. 2018

Seminars in Cell & Developmental Biology

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It is conceivable that spermatid apico-basal polarity and spermatid planar cell polarity (PCP) are utmost important to support spermatogenesis. The orderly arrangement of developing germ cells in particular spermatids during spermiogenesis are essential to obtain structural and nutrient supports from the fixed number of Sertoli cells across the limited space of seminiferous epithelium in the tubules following Sertoli cell differentiation by ∼17 day postpartum (dpp) in rodents and ∼12 years of age at puberty in humans. Yet few studies are found in the literature to investigate the role of these proteins to support spermatogenesis. Herein, we briefly summarize recent findings in the field, in particular emerging evidence that supports the concept that apico-basal polarity and PCP are conferred by the corresponding polarity proteins through their effects on the actin- and microtubule (MT)-based cytoskeletons. While much research is needed to bridge our gaps of understanding cell polarity, cytoskeletal function, and signaling proteins, a critical evaluation of some latest findings as summarized herein provides some important and also thought-provoking concepts to design better functional experiments to address this important, yet largely expored, research topic.

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“…The aforementioned findings reveal an important, cellautonomous function of Vangl2 in promoting Wnt signaling, in contrast to its complex non-autonomous requirement in Drosophila embryonic epithelia that involves interaction with Frizzled proteins in the neighboring cells (Bailly et al, 2017;Devenport, 2014). To explore how Vangl2 tunes Wnt signaling to regulate neuronal development, and whether Vangl2-dependent Frizzled internalization occurs in broader, more diverse cellular contexts, we systemically analyze the functions of C. elegans vang-1 gene in multiple classes of migrating C. elegans neurons.…”

Section: Introductionmentioning

confidence: 99%

The polarity protein VANG-1 antagonizes Wnt signaling by facilitating Frizzled endocytosis

Liao

Chen

et al. 2018

Development

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Signaling that instructs the migration of neurons needs to be tightly regulated to ensure precise positioning of neurons and subsequent wiring of the neuronal circuits. Wnt-Frizzled signaling controls neuronal migration in metazoans, in addition to many other aspects of neural development. We show that Caenorhabditis elegans VANG-1, a membrane protein that acts in the planar cell polarity (PCP) pathway, antagonizes Wnt signaling by facilitating endocytosis of the Frizzled receptors. Mutations of vang-1 suppress migration defects of multiple classes of neurons in the Frizzled mutants, and overexpression of vang-1 causes neuronal migration defects similar to those of the Frizzled mutants. Our genetic experiments suggest that VANG-1 facilitates Frizzled endocytosis through β-arrestin2. Co-immunoprecipitation experiments indicate that Frizzled proteins and VANG-1 form a complex, and this physical interaction requires the Frizzled cysteine-rich domain. Our work reveals a novel mechanism mediated by the PCP protein VANG-1 that downregulates Wnt signaling through Frizzled endocytosis.

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The planar cell polarity Vangl2 protein: From genetics to cellular and molecular functions

Cited by 46 publications

References 89 publications

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

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

Regulation of spermatid polarity by the actin- and microtubule (MT)-based cytoskeletons

The polarity protein VANG-1 antagonizes Wnt signaling by facilitating Frizzled endocytosis

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