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Auswahl der wissenschaftlichen Literatur zum Thema „Planar Cellular Polarity (PCP)“
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Zeitschriftenartikel zum Thema "Planar Cellular Polarity (PCP)"
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Devenport, Danelle. „The cell biology of planar cell polarity“. Journal of Cell Biology 207, Nr. 2 (27.10.2014): 171–79. http://dx.doi.org/10.1083/jcb.201408039.
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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.
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Axelrod, Jeffrey D., und Helen McNeill. „Coupling Planar Cell Polarity Signaling to Morphogenesis“. Scientific World JOURNAL 2 (2002): 434–54. http://dx.doi.org/10.1100/tsw.2002.105.
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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.
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Mlodzik, Marek. „Planar cell polarity: moving from single cells to tissue-scale biology“. Development 147, Nr. 24 (15.12.2020): dev186346. http://dx.doi.org/10.1242/dev.186346.
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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.
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Tower-Gilchrist, Cristy, Stephanie A. Zlatic, Dehong Yu, Qing Chang, Hao Wu, Xi Lin, Victor Faundez und Ping Chen. „Adaptor protein-3 complex is required for Vangl2 trafficking and planar cell polarity of the inner ear“. Molecular Biology of the Cell 30, Nr. 18 (15.08.2019): 2422–34. http://dx.doi.org/10.1091/mbc.e16-08-0592.
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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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Padmanabhan, Krishnanand, Hanna Grobe, Jonathan Cohen, Arad Soffer, Adnan Mahly, Orit Adir, Ronen Zaidel-Bar und Chen Luxenburg. „Thymosin β4 is essential for adherens junction stability and epidermal planar cell polarity“. Development 147, Nr. 23 (01.12.2020): dev193425. http://dx.doi.org/10.1242/dev.193425.
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ABSTRACTPlanar cell polarity (PCP) is essential for tissue morphogenesis and homeostasis; however, the mechanisms that orchestrate the cell shape and packing dynamics required to establish PCP are poorly understood. Here, we identified a major role for the globular (G)-actin-binding protein thymosin-β4 (TMSB4X) in PCP establishment and cell adhesion in the developing epidermis. Depletion of Tmsb4x in mouse embryos hindered eyelid closure and hair-follicle angling owing to PCP defects. Tmsb4x depletion did not preclude epidermal cell adhesion in vivo or in vitro; however, it resulted in abnormal structural organization and stability of adherens junction (AJ) due to defects in filamentous (F)-actin and G-actin distribution. In cultured keratinocytes, TMSB4X depletion increased the perijunctional G/F-actin ratio and decreased G-actin incorporation into junctional actin networks, but it did not change the overall actin expression level or cellular F-actin content. A pharmacological treatment that increased the G/F-actin ratio and decreased actin polymerization mimicked the effects of Tmsb4x depletion on both AJs and PCP. Our results provide insights into the regulation of the actin pool and its involvement in AJ function and PCP establishment.
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Kim, Su Kyoung, Asako Shindo, Tae Joo Park, Edwin C. Oh, Srimoyee Ghosh, Ryan S. Gray, Richard A. Lewis et al. „Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis“. Science 329, Nr. 5997 (29.07.2010): 1337–40. http://dx.doi.org/10.1126/science.1191184.
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The planar cell polarity (PCP) signaling pathway governs collective cell movements during vertebrate embryogenesis, and certain PCP proteins are also implicated in the assembly of cilia. The septins are cytoskeletal proteins controlling behaviors such as cell division and migration. Here, we identified control of septin localization by the PCP protein Fritz as a crucial control point for both collective cell movement and ciliogenesis in Xenopus embryos. We also linked mutations in human Fritz to Bardet-Biedl and Meckel-Gruber syndromes, a notable link given that other genes mutated in these syndromes also influence collective cell movement and ciliogenesis. These findings shed light on the mechanisms by which fundamental cellular machinery, such as the cytoskeleton, is regulated during embryonic development and human disease.
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Babayeva, Sima, Yulia Zilber und Elena Torban. „Planar cell polarity pathway regulates actin rearrangement, cell shape, motility, and nephrin distribution in podocytes“. American Journal of Physiology-Renal Physiology 300, Nr. 2 (Februar 2011): F549—F560. http://dx.doi.org/10.1152/ajprenal.00566.2009.
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Glomerular podocytes are highly polarized cells characterized by dynamic actin-based foot processes (FPs). Neighboring FPs form specialized junctions, slit diaphragms (SDs), which prevent passage of proteins into the ultrafiltrate. The SD protein complex is linked to cytoskeletal actin filaments and mutations in SD proteins lead to a dramatic change in cell morphology; proteinuria is accompanied by FP retraction and loss of SD structure. Thus, organization of the podocyte cytoskeleton is tightly linked to filtration barrier function. In a variety of cell systems, cytoskeleton arrangement is regulated by the planar cell polarity (PCP) pathway. PCP signals lead to the appearance of highly organized cellular structures that support directional cell movement and oriented cell division. Derangement of the PCP pathway causes neural tube defects and cystic kidney disease in mice. Here, we establish that the PCP pathway regulates the cytoskeleton of podocytes. We identify expression of core PCP proteins in mouse kidney sections and of PCP transcripts in murine and human cultured podocytes. The pathway is functional since Wnt5a causes redistribution of PCP proteins Dishevelled and Daam1. We also show that Wnt5a treatment changes podocyte morphology, alters nephrin distribution, increases the number of stress fibers, and increases cell motility. In reciprocal experiments, siRNA depletion of the core PCP gene Vangl2 reduced the number of cell projections and decreased stress fibers and cell motility. Finally, we demonstrate direct interactions between Vangl2 and the SD protein, MAGI-2. This suggests that the PCP pathway may be directly linked to organization of the SD as well as to regulation of podocyte cytoskeleton. Our observations indicate that PCP signaling may play an important role both in podocyte development and FP cytoskeleton dynamics.
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Zilber, Yulia, Sima Babayeva, Jung Hwa Seo, Jia Jia Liu, Steven Mootin und Elena Torban. „The PCP effector Fuzzy controls cilial assembly and signaling by recruiting Rab8 and Dishevelled to the primary cilium“. Molecular Biology of the Cell 24, Nr. 5 (März 2013): 555–65. http://dx.doi.org/10.1091/mbc.e12-06-0437.
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The planar cell polarity (PCP) pathway controls multiple cellular processes during vertebrate development. Recently the PCP pathway was implicated in ciliogenesis and in ciliary function. The primary cilium is an apically projecting solitary organelle that is generated via polarized intracellular trafficking. Because it acts as a signaling nexus, defects in ciliogenesis or cilial function cause multiple congenital anomalies in vertebrates. Loss of the PCP effector Fuzzy affects PCP signaling and formation of primary cilia; however, the mechanisms underlying these processes are largely unknown. Here we report that Fuzzy localizes to the basal body and ciliary axoneme and is essential for ciliogenesis by delivering Rab8 to the basal body and primary cilium. Fuzzy appears to control subcellular localization of the core PCP protein Dishevelled, recruiting it to Rab8-positive vesicles and to the basal body and cilium. We show that loss of Fuzzy results in inhibition of PCP signaling and hyperactivation of the canonical WNT pathway. We propose a mechanism by which Fuzzy participates in ciliogenesis and affects both canonical WNT and PCP signaling.
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Gault, William J., Patricio Olguin, Ursula Weber und Marek Mlodzik. „Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking“. Journal of Cell Biology 196, Nr. 5 (05.03.2012): 605–21. http://dx.doi.org/10.1083/jcb.201107137.
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Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes.
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Gajos-Michniewicz, Anna, und Malgorzata Czyz. „WNT Signaling in Melanoma“. International Journal of Molecular Sciences 21, Nr. 14 (09.07.2020): 4852. http://dx.doi.org/10.3390/ijms21144852.
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WNT-signaling controls important cellular processes throughout embryonic development and adult life, so any deregulation of this signaling can result in a wide range of pathologies, including cancer. WNT-signaling is classified into two categories: β-catenin-dependent signaling (canonical pathway) and β-catenin-independent signaling (non-canonical pathway), the latter can be further divided into WNT/planar cell polarity (PCP) and calcium pathways. WNT ligands are considered as unique directional growth factors that contribute to both cell proliferation and polarity. Origin of cancer can be diverse and therefore tissue-specific differences can be found in WNT-signaling between cancers, including specific mutations contributing to cancer development. This review focuses on the role of the WNT-signaling pathway in melanoma. The current view on the role of WNT-signaling in cancer immunity as well as a short summary of WNT pathway-related drugs under investigation are also provided.
Dissertationen zum Thema "Planar Cellular Polarity (PCP)"
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Barrott, Jared James. „Wnt5a Signaling Independently of the Planar Cell Polarity Pathway Resulting in Convergent Extension and Neural Tube Closure During Vertebrate Development“. Diss., CLICK HERE for online access, 2008. http://contentdm.lib.byu.edu/ETD/image/etd2612.pdf.
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Boëx, Myriam. „Implication d’une nouvelle voie de signalisation médiée par le complexe MuSK/Vangl2 dans la connectivité neuromusculaire“. Electronic Thesis or Diss., Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2020SORUS258.pdf.
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Le contact anatomique et fonctionnel qui s’établit entre la terminaison axonale d’un motoneurone et une région spécialisée de la fibre musculaire striée squelettique est appelé jonction neuromusculaire (JNM). Le développement de la synapse neuromusculaire périphérique implique une communication dynamique via divers processus de signalisation réciproques entre les motoneurones et leurs cibles musculaires. Parmi les facteurs sécrétés qui orchestrent cette coordination trans-synaptique, les morphogènes Wnt constituent des signaux critiques pour la différenciation synaptique, cependant les mécanismes moléculaires qui sous-tendent l’action des Wnt à la JNM des mammifères restent encore largement inconnus et controversés. Mon travail de thèse a porté sur 1) la validation du rôle critique des signalisations Wnt médiées par le récepteur muscle spécifique MuSK in vivo et 2) l’étude de la voie de signalisation Wnt de polarité cellulaire planaire (PCP) dans la mise en place et la maintenance de la JNM des mammifères. Notre équipe a récemment montré qu’un effecteur principal de cette voie PCP, nommé Van Gogh-like protein 2 (Vangl2) est enrichi à la JNM, à la fois dans les compartiments pré- et postsynaptique et que Vangl2 est capable de lier certains ligands Wnt. J’ai montré que la protéine Vangl2 musculaire joue un rôle critique dans le développement et le maintien de l’intégrité de la synapse neuromusculaire en contrôlant le niveau d’activité de la signalisation MuSK. L’ensemble de mes résultats a révélé l’existence d’une nouvelle voie de signalisation Wnt PCP dans le muscle, reposant sur l'interaction Vangl2/MuSK, impliquée dans l’assemblage et l’intégrité postsynaptiqueThe neuromuscular junction (JNM) is a peripheral synapse formed by the anatomic and functional contact between a motor neuron and a striated skeletal muscle fiber. NMJ development requires a dynamic communication between motor axons and their muscle targets through several reciprocal signaling. Among the limited number of secreted factors that orchestrate this trans-synaptic coordination, the Wnts diffusible cues have emerged as critical signals for synaptic differentiation, yet how Wnt signaling drives NMJ formation and maintenance remain poorly understood and controversial in mammals. In this context, the aims of my PhD project were 1) to validate the functional role of Wnt-MuSK interaction in vivo and 2) to study the Wnt Planar Cell Polarity (PCP) pathway during NMJ assembly and maintenance in mammals. Interestingly, our team showed that Van Gogh-like protein 2 (Vangl2), a core PCP component, is accumulated at developing NMJ, at both pre- and postsynaptic sites. Moreover, Vangl2 interacts with a subset of Wnt morphogens that are secreted at the NMJ suggesting that a Wnt/Vangl2-PCP signaling is involved in NMJ development. By using a set of mutant mice along with a large panel of cell biological and biochemical assays, I found that muscle Vangl2 is critical for NMJ assembly and maintenance, by controlling the level of MuSK signaling activity. Collectively, my results uncover a new Wnt/PCP signaling in the muscle, relying on Vangl2/MuSK interaction that shapes neuromuscular connectivity by regulating postsynaptic assembly and integrity
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Watson, Julia Alice. „Investigating the role of Wnt/Planar cell polarity (PCP) in Neuromesodermal Progenitors (NMPs)“. Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31193.
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Neuromesodermal progenitors (NMPs) are bipotent progenitors, located at the caudal end of the embryo and are essential for axis formation. These stem cell-like progenitors possess the ability to self-renew and differentiate to both mesodermal and neural lineages, such as skeletal muscle and spinal cord derivatives. These progenitors arise at E8.5 and are localised in the caudal lateral epiblast (CLE), a posterior region of the embryo near the primitive streak. Later in development, they reside in the tail bud until cessation of axial elongation at E13.5. Throughout these stages NMPs are characteristically marked by co-expression of T(Bra) (Brachyury) and Sox2. This characteristic is also present in in vitro NMPs, which can be derived from Epiblast Stem Cells (EpiSCs) through treatment with Wnt/β-catenin signalling agonists and Fgf2, which simulates their in vivo environment. Protein and mRNA profiling of NMPs and mutant phenotypes in vivo supports the hypothesis that a non-canonical Wnt pathway, the Wnt/Planar Cell Polarity pathway (PCP) could be involved in NMP fate decision and/or maintenance. This thesis focuses on understanding more about the role of PCP by aiming to identify the spatio-temporal profile of Wnt/PCP pathway components in NMP regions during axial elongation, as well as determining its role in NMP behaviour through manipulation of this pathway via in vivo and in vitro assays Employing in situ hybridisation and immunohistochemistry techniques, key Wnt/PCP components, including Pk1, Vangl2 and Ptk7, were confirmed to be present in in vivo and in vitro NMPs, thus, providing strong evidence that Wnt/PCP may be involved regulating NMP behaviour. Disruption of Wnt/PCP signalling through overexpression of Wnt/PCP components was tested in refined in vivo and in vitro assays. Overexpression of Vangl2 and Ptk7, but not Pk1 in NMPs regions in vivo resulted in loss of contribution to neural lineages, as well as lower contribution to NMP regions themselves. Similarly, Wnt/PCP components were disrupted in vitro through generation of dox-inducible overexpression cells lines for Wnt/PCP components. These lines were used to generate NMPs from an optimised novel alternative source Epiblast-Like Cells (EpiLCs), however no clear affect to lineage was observed. Overall this work has successfully advanced our knowledge of Wnt/PCP mediated control of NMP differentiation and maintenance, and provided a finer grained description of the relationships between them.
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Giese, Arnaud. „Régulation de la protéine centrale de la polarité planaire cellulaire Vangl2 dans l’organe de Corti“. Thesis, Bordeaux 2, 2010. http://www.theses.fr/2010BOR21761/document.
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Outre leur polarité apico-basale, certaines cellules épithéliales développent une seconde polarité, appelée Polarité Planaire Cellulaire (PCP). L'axe de la PCP est orienté perpendiculairement à l'axe de polarité apico-basale et régit l'orientation uniforme de certaines structures, comme les poils ou cils, non seulement à l'échelle de la cellule mais également au sein du tissu. L'épithélium cochléaire est l'un des meilleurs modèles d'étude de PCP chez les mammifères. En effet, les cellules neuro-épitheliales qui le composent, soutenues par des cellules de soutien, présentent à leur apex, des touffes ciliaires dont l'orientation est parfaitement coordonnée par la voie de la polarité planaire. Les deux premiers gènes impliqués dans la PCP chez les mammifères, Vangl2 et Scrib1, ont été identifiés sur la base du phénotype de la cochlée chez les mutants. L'analyse de la localisation de Vangl2 dans l'organe de Corti a également révélé une localisation asymétrique proximo-distale et transitoire de la protéine, perpendiculaire à l'axe apico-basal classique. Cette asymétrie apparaît à la jonction entre deux types cellulaires : une cellule sensorielle ciliée et une cellule de soutien. J'ai pu montrer au cours de mes travaux de thèse que cette asymétrie était majoritairement due à une accumulation de Vangl2 du côté distal des cellules de soutien, et que dans une moindre mesure, Vangl2 pouvait ségréger du côté distal des cellules ciliées. Cette localisation subcellulaire très précise et limitée dans l'espace semble être indépendante de l'expression du gène Scrib1 dans les cellules ciliées. La délétion du gène Scrib1 dans les cellules ciliées m'a toutefois permis de mettre en évidence que ce gène avait un rôle autonome dans la régulation de la PCP, et que les cellules de soutien de l'organe de Corti pouvaient jouer un rôle prépondérant dans le contrôle de la PCP. Mes travaux ont également permis de mettre en évidence que GIPC1 avait un rôle dans la régulation de la PCP et le maintien de l'intégrité des touffes ciliaires des cellules sensorielles, et que le complexe GIPC1/Myosine VI pouvait réguler l'établissement de l'asymétrie de Vangl2 dans l'organe de CortiSeveral epithelia exhibit a second polarity perpendicular to the apico-basal axis, called planar polarity and that governs the orientation of structures such as stereocilia and hear. Our laboratory studies planar polarity, using mammalian cochlear sensory epithelium and we focus our studies on Vangl2, that we identified as the first mammalian planar polarity gene. Vangl2 encodes a four-transmembrane protein that contains a PDZ binding domain in its C-terminus tail. Vangl2 is asymmetrically located at the junction between mechanosensory hair cells and supporting cells, and this asymmetry appears important for planar cell polarity. I have shown in my thesis, using STED microscopy, that Vangl2 asymmetry is mainly due to an accumulation of Vangl2 to the distal side of supporting cells. I sought to dissect the molecular role of Vangl2 by analysing its trafficking within the cochlear epithelium. Deletion analysis shows that the last 12 amino acids, unlike its N-terminus tail are essential for Vangl2 endoplasmic reticulum sorting, its plasma membrane targeting and its function. Conditional mutant mice analysis show that Scrib1, which we have previously shown, interacts with Vangl2 through the PDZ binding domain of its C-terminal tail, is not the protein mediating this asymmetry. My work also highlight that GIPC1 had a role in the regulation of PCP and maintaining the integrity of hair bundles of sensory cells, and that the complex GIPC1/Myosin VI could regulate Vangl2 asymmetry in the organ of Corti
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Martinez, Sébastien. „Rôle de la protéine tyrosine kinase 7 dans le cancer colorectal et la polarité planaire cellulaire“. Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4019.
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La voie de signalisation WNT/PCP, couramment associée à la polarité planaire cellulaire, joue un rôle fondamental dans la morphogenèse chez les vertébrés. Parmi les différents composants protéiques de la voie WNT/PCP, on retrouve la protéine tyrosine kinase 7 (PTK7), dont les fonctions restent encore très peu décrites. Au cours de ma thèse, j’ai montré que PTK7 interagissait avec le récepteur tyrosine kinase ROR2. Ce complexe, après fixation du ligand WNT5A, induit la migration de fibroblastes embryonnaires murins via l’activation de JNK. Au cours du développement embryonnaire du xénope, Ptk7 interagit de manière fonctionnelle avec Ror2, et contrôle l’expression de la protocadhérine Papc ainsi que la morphogénèse. De plus, en utilisant une approche de Tissue MicroArray, réalisée sur des patients atteints de cancers colorectaux, j’ai pu montrer que PTK7 était retrouvé surexprimé chez 34% des patients, et que cette surexpression était un facteur de mauvais pronostic. Dans des lignées cellulaires issues de cancers colorectaux, la suppression de PTK7 par shRNA entraine une diminution de la migration des cellules tumorales, mais n’impacte pas leur prolifération et leur résistance aux drogues anticancéreuses. Dans un modèle de xénogreffe murin, la suppression de PTK7 induit une diminution du développement tumoral et l’expression de ce dernier, dans des cellules négative pour PTK7, entraine une augmentation de l’apparition de métastases chez les animaux injectés. Ce travail apporte de nouveaux éclaircissements sur le du récepteur PTK7 dans la voie de signalisation WNT/PCP, et le définit comme potentiel biomarqueur et cible thérapeutique dans le cancer colorectalThe non-canonical WNT/planar cell polarity (WNT/PCP) pathway plays important roles in morphogenetic processes in vertebrates. Among WNT/PCP components, protein tyrosine kinase 7 (PTK7) is a tyrosine kinase receptor with poorly defined functions lacking catalytic activity. We show that PTK7 associates with receptor tyrosine kinase-like orphan receptor 2 (ROR2) to form a heterodimeric complex in mammalian cells and physically and functionally interact with the non-canonical WNT5A ligand, leading to JNK activation and cell movements. In the Xenopus embryo, Ptk7 functionally interacts with Ror2 to regulate protocadherin papc expression and morphogenesis. Furthermore, we show that Ptk7 is required for papc activation induced by Wnt5a and that Wnt5a stimulates the release of the Ptk7 intracellular domain, which can translocate into the nucleus and activate papc expression. Moreover, using a Tissue MicroArray produced from CRC patients we correlated PTK7 expression with pathological features and patient outcome. PTK7 was significantly up-regulated in CRC tissue, and its overexpression was found in 34% of patients. In CRC cell lines, shRNA PTK7 reduced migration, but did not affect cell proliferation and resistance to drugs. In a xenograft mouse model, downregulation of PTK7 led to reduced tumor growth, whereas its overexpression in PTK7-negative cancer cells led to increased metastatic events. This work reveals novel molecular mechanisms of action of PTK7 in non-canonical WNT/PCP signaling that may promote cell and tissue movements and define PTK7 expression as a potential prognostic biomarker and a novel therapeutic target in CRC
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Godfrey, Grayland W. II. „Characterizing the Role of Key Planar Cell Polarity Pathway Components in Axon Guidance“. VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4841.
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An essential process to the development of the neural network of the nervous system is axon guidance. The noncanonical Wnt/Planar Cell Polarity pathway has been identified as an integral component in controlling the projection of axons during axon guidance. Prickle, ROR1 and ROR2 are PCP related proteins that do not have clearly defined roles in the process. This study aims to use zebrafish CoPA neurons as a model to study the roles of Prickle, ROR1, and ROR2 in axon guidance. Using in situ hybridization, morpholino knockdown, and CRISPR/Cas9 loss of function experiments were able to identify ror1, ror2 and prickle as potential required components in CoPA neuron axon guidance. Elucidating the role of these protein in axon guidance not only will increase our knowledge of the PCP pathway but it will also increase our understanding of the development of the nervous system.
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Tanner, Raymond. „A Role for the Planar Cell Polarity Pathway in Neuronal Positioning Along the AP Axis of C. elegans“. Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31521.
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We sought to investigate the role of the Planar Cell Polarity (PCP) pathway in neuronal positioning along the Anterior-Posterior (AP) axis of C. elegans, and chose the worm’s DD-type motor neurons as a model. The six DD neurons (DD1-DD6) are evenly spaced in the ventral nerve cord of wild type animals. Here we showed that mutations in core PCP genes caused DD neuron spacing and positioning defects. prkl-1 double mutant combinations with vang-1 and fmi-1 showed a suppression of the more severe prkl-1 single mutant defects, which was evidence of genetic interactions between these PCP components. We also conducted a candidate screen of Frizzled, Dishevelled, Wnt, and ROCK genes, and found that dsh-1/Dishevelled, mom-2/Wnt and let-502/ROCK also played roles in DD neuronal positioning. Both vang-1 and prkl-1 were found to function within the nervous system to guide DD neuronal positioning, and prkl-1 was further identified as playing a cell autonomous role. The origins of observed DD neuron anterior positioning defects were investigated during embryogenesis, in which 1.5 fold stage prkl-1(ok3182) embryos displayed delayed intercalation of the DD neurons. This represents a novel role for the PCP pathway in mediating DD neuronal intercalation.
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Schäfer, Simon Thomas [Verfasser]. „ATP6AP2 is critically involved in adult hippocampal neurogenesis and reveals stage-specific functions for Wnt/ß-Catenin and Wnt/Planar Cell Polarity (PCP) signaling / Simon Thomas Schäfer“. Greifswald : Universitätsbibliothek Greifswald, 2015. http://d-nb.info/1069389331/34.
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Allen, John C. „FGF4 Induced Wnt5a Gradient in the Limb Bud Mediates Mesenchymal Cell Directed Migration and Division“. BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4309.
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The AER has a vital role in directing embryonic limb development. Several models have been developed that attempt to explain how the AER directs limb development, but none of them are fully supported by existing data. I provide evidence that FGFs secreted from the AER induce a gradient of Wnt5a. I also demonstrate that limb mesenchyme grows toward increasing concentrations of Wnt5a. We hypothesize that the changing shape of the AER is critical for patterning the limb along the proximal to distal axis. To better understand the pathway through which Wnt5a elicits its effects, we have performed various genetic studies. We demonstrate that Wnt5a does not signal via the Wnt/β-catenin pathway. However, we show that Wnt5a mutants share many common defects with Vangl2 mutants suggesting that Wnt5a signals through the Wnt/planar cell polarity (PCP) pathway.
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El-Hassan, Abdul-Rahman. „Caractérisation moléculaire et fonctionnelle d'un nouvel allèle du gène de la polarité cellulaire planaire (PCP) Vangl2“. Thèse, 2017. http://hdl.handle.net/1866/20536.
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Zaffran, Stéphane. Cardiac growth II: Cardiomyocyte polarization. Herausgegeben von José Maria Pérez-Pomares, Robert G. Kelly, Maurice van den Hoff, José Luis de la Pompa, David Sedmera, Cristina Basso und Deborah Henderson. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198757269.003.0010.
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During vertebrate embryogenesis, the planar cell polarity (PCP) signalling pathway is responsible for cell movements essential for convergent extension during gastrulation, neural tube closure, neural crest cell migration, and heart morphogenesis. In the heart, the non-canonical Wnt/PCP pathway regulates cell polarity, cell shape, and cell dynamics during formation of the cardiac crescent and deployment of second heart field cardiac progenitors to the poles of the heart tube. PCP signalling is also essential for the establishment of left–right patterning in the early embryo. This chapter reviews our current understanding of PCP signalling in heart morphogenesis and how it affects the pathogenesis of congenital heart diseases.
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Kühn, Wolfgang, und Gerd Walz. The molecular basis of ciliopathies and cyst formation. Herausgegeben von Neil Turner. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0303.
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Abnormalities of the cilium, termed ‘ciliopathies’, are the prime suspect in the pathogenesis of renal cyst formation because the gene products of cystic disease-causing genes localize to them, or near them. However, we only partially understand how cilia maintain the geometry of kidney tubules, and how abnormal cilia lead to renal cysts, and the diverse range of diseases attributed to them. Some non-cystic diseases share pathology of the same structures. Although still incompletely understood, cilia appear to orient cells in response to extracellular cues to maintain the overall geometry of a tissue, thereby intersecting with the planar cell polarity (PCP) pathway and the actin cytoskeleton. The PCP pathway controls two morphogenetic programmes, oriented cell division (OCD) and convergent extension (CE) through cell intercalation that both seem to play a critical role in cyst formation. The two-hit theory of cystogenesis, by which loss of the second normal allele causes tubular epithelial cells to form kidney cysts, has been largely borne out. Additional hits and influences may better explain the rate of cyst formation and inter-individual differences in disease progression. Ciliary defects appear to converge on overlapping signalling modules, including mammalian target of rapamycin and cAMP pathways, which can be targeted to treat human cystic kidney disease irrespective of the underlying gene mutation.
Buchteile zum Thema "Planar Cellular Polarity (PCP)"
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Moreira, Sofia, Jaime A. Espina, Joana E. Saraiva und Elias H. Barriga. „A Toolbox to Study Tissue Mechanics In Vivo and Ex Vivo“. In Methods in Molecular Biology, 495–515. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2035-9_29.
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AbstractDuring vertebrate embryogenesis, tissues interact and influence each other’s development to shape an embryo. While communication by molecular components has been extensively explored, the role of mechanical interaction between tissues during embryogenesis is just starting to be revealed. Addressing mechanical involvement in morphogenesis has traditionally been challenging mainly due to the lack of proper tools to measure and modify mechanical environments of cells in vivo. We have recently used atomic force microscopy (AFM) to show that the migration of the Xenopus laevis cephalic neural crest cells is triggered by stiffening of the mesoderm, a tissue that neural crest cells use as a migratory substrate in vivo. Interestingly we showed that the activity of the planar cell polarity (PCP) pathway is required to mediate this novel mechanical interaction between two tissues. In this chapter, we share the toolbox that we developed to study the role of PCP signaling in mesoderm cell accumulation and stiffening (in vivo) as well as the impact of mesoderm stiffness in promoting neural crest cell polarity and migration (ex vivo). We believe that these tools can be of general use for investigators interested in addressing the role of mechanical inputs in vivo and ex vivo.
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„Planar Cell Polarity (PCP)“. In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 1502. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_12937.
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Gao, Bo. „Wnt Regulation of Planar Cell Polarity (PCP)“. In Planar Cell Polarity During Development, 263–95. Elsevier, 2012. http://dx.doi.org/10.1016/b978-0-12-394592-1.00008-9.
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Boutin, Camille, André M. Goffinet und Fadel Tissir. „Celsr1–3 Cadherins in PCP and Brain Development“. In Planar Cell Polarity During Development, 161–83. Elsevier, 2012. http://dx.doi.org/10.1016/b978-0-12-394592-1.00010-7.
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Asad, Mohammad, Meng Kang Wong, Tuan Zea Tan, David Virshup, Jean Paul Thiery und Ruby Yun-Ju Huang. „Abstract A30: Frizzled-7 (FZD7)-mediated non-canonical Wnt-Planar Cell Polarity (PCP) signalling pathway as a novel molecular driver for the C5/Proliferative/Stem-A molecular subtype of ovarian cancer.“ In Abstracts: AACR Special Conference: Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; October 17-20, 2015; Orlando, FL. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1557-3265.ovca15-a30.
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