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.

scholarly journals Coupling Planar Cell Polarity Signaling to Morphogenesis

2002 ◽  
Vol 2 ◽  
pp. 434-454 ◽  
Author(s):  
Jeffrey D. Axelrod ◽  
Helen McNeill
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Fruit Fly ◽  
Convergent Extension ◽  
Cytoskeletal Reorganization ◽  
Directional Information ◽  
Cochlear Hair Cell ◽  
Cellular Asymmetry ◽  
Pcp Signaling ◽  
Unknown Signal

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.

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 Distinct Apical and Basolateral Mechanisms Drive Planar Cell Polarity-Dependent Convergent Extension of the Mouse Neural Plate

2014 ◽  
Vol 29 (1) ◽  
pp. 34-46 ◽  
Author(s):  
Margot Williams ◽  
Weiwei Yen ◽  
Xiaowei Lu ◽  
Ann Sutherland
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Neural Plate ◽  
Convergent Extension

scholarly journals The Drosophila Neurogenin, Tap, controls axonal growth through the Wnt adaptor protein Dishevelled

2015 ◽  
Author(s):  
Liqun Yuan ◽  
Shu Hu ◽  
Zeynep Okray ◽  
Xi Ren ◽  
Natalie De Geest ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Cell Polarity ◽  
Mushroom Body ◽  
Planar Cell Polarity ◽  
Adaptor Protein ◽  
Axonal Growth ◽  
Neurite Growth ◽  
Fine Regulation ◽  
Early Neurogenesis

AbstractThe Neurogenin (Ngn) transcription factors control early neurogenesis and neurite outgrowth in mammalian cortex. In contrast to their proneural activity, their function in neurite growth is poorly understood. Drosophila has a single predicted Ngn homologue called Tap, whose function is completely unknown. Here we show that Tap is not a proneural protein in Drosophila but is required for proper axonal growth and guidance of neurons of the mushroom body (MB), a neuropile required for associative learning and memory. Genetic and expression analyses suggest that Tap inhibits excessive axonal growth by fine regulation of the levels of the Wnt signaling adaptor protein, Dishevelled.SummaryThe Drosophila Neurogenin homologue, Target of Pox neuro (Tap), prevents axonal overgrowth by regulating the Wnt Planar Cell Polarity pathway adaptor protein Dishevelled.

Van Gogh-like2 (Strabismus) and its role in planar cell polarity and convergent extension in vertebrates

2004 ◽  
Vol 20 (11) ◽  
pp. 570-577 ◽  
Author(s):  
Elena Torban ◽  
Christine Kor ◽  
Philippe Gros
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Convergent Extension ◽  
Van Gogh

scholarly journals Self-assembly, buckling and density-invariant growth of three-dimensional vascular networks

2019 ◽  
Vol 16 (159) ◽  
pp. 20190517 ◽  
Author(s):  
Julius B. Kirkegaard ◽  
Bjarke F. Nielsen ◽  
Ala Trusina ◽  
Kim Sneppen
Keyword(s):  
Cell Polarity ◽  
Self Assembly ◽  
Planar Cell Polarity ◽  
Vascular System ◽  
Initial Density ◽  
Three Dimensional ◽  
Three Dimensions ◽  
Emergent Properties ◽  
Vascular Density ◽  
Convergent Extension

The experimental actualization of organoids modelling organs from brains to pancreases has revealed that much of the diverse morphologies of organs are emergent properties of simple intercellular ‘rules’ and not the result of top-down orchestration. In contrast to other organs, the initial plexus of the vascular system is formed by aggregation of cells in the process known as vasculogenesis. Here we study this self-assembling process of blood vessels in three dimensions through a set of simple rules that align intercellular apical–basal and planar cell polarity. We demonstrate that a fully connected network of tubes emerges above a critical initial density of cells. Through planar cell polarity, our model demonstrates convergent extension, and this polarity furthermore allows for both morphology-maintaining growth and growth-induced buckling. We compare this buckling with the special vasculature of the islets of Langerhans in the pancreas and suggest that the mechanism behind the vascular density-maintaining growth of these islets could be the result of growth-induced buckling.

scholarly journals Wnt-11 and Fz7 reduce cell adhesion in convergent extension by sequestration of PAPC and C-cadherin

2012 ◽  
Vol 198 (4) ◽  
pp. 695-709 ◽  
Author(s):  
Bianca Kraft ◽  
Corinna D. Berger ◽  
Veronika Wallkamm ◽  
Herbert Steinbeisser ◽  
Doris Wedlich
Keyword(s):  
Cell Adhesion ◽  
Xenopus Laevis ◽  
Cell Polarity ◽  
Cell Sorting ◽  
Planar Cell Polarity ◽  
Convergent Extension ◽  
Membrane Stabilization ◽  
Dynamic Modulation ◽  
Interaction Domains ◽  
Shape Changes

Wnt-11/planar cell polarity signaling polarizes mesodermal cells undergoing convergent extension during Xenopus laevis gastrulation. These shape changes associated with lateral intercalation behavior require a dynamic modulation of cell adhesion. In this paper, we report that Wnt-11/frizzled-7 (Fz7) controls cell adhesion by forming separate adhesion-modulating complexes (AMCs) with the paraxial protocadherin (PAPC; denoted as AMCP) and C-cadherin (denoted as AMCC) via distinct Fz7 interaction domains. When PAPC was part of a Wnt-11–Fz7 complex, its Dynamin1- and clathrin-dependent internalization was blocked. This membrane stabilization of AMCP (Fz7/PAPC) by Wnt-11 prevented C-cadherin clustering, resulting in reduced cell adhesion and modified cell sorting activity. Importantly, Wnt-11 did not influence C-cadherin internalization; instead, it promoted the formation of AMCC (Fz7/Cadherin), which competed with cis-dimerization of C-cadherin. Because PAPC and C-cadherin did not directly interact and did not form a joint complex with Fz7, we suggest that Wnt-11 triggers the formation of two distinct complexes, AMCC and AMCP, that act in parallel to reduce cell adhesion by hampering lateral clustering of C-cadherin.

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