scholarly journals Planar Cell Polarity: The Frizzled Homophobic Signal

2019 ◽  
Author(s):  
José-Eduardo Gomes
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Spatial Information ◽  
Transmembrane Protein ◽  
Adjacent Cell ◽  
Signaling Mechanism ◽  
Insect Wing ◽  
Crucial Feature ◽  
Pcp Signaling ◽  
Core Genes

The cell’s capacity to integrate and respond to spatial information is a crucial feature of morphogenesis and development. The Planar Cell Polarity (PCP) pathway is a signaling mechanism, widely conserved across metazoans, providing spatial orientation along the plane of an epithelium in morphogenic processes ranging from insect wing patterning to mammalian cochleae. Although the core genes involved in the PCP pathway have been molecularly identified in the 1990s, the PCP signaling mechanism remains controversial. In this article I discuss the main players and previous models of PCP signaling reported in the literature, and propose a new model. According to it PCP is established through an homophobic signal by transmembrane protein Frizzled (Fz): 1) a Fz signal in one cell repeals Fz itself in the adjacent cell, thereby generating symmetry breaking; 2) the instructive PCP signal is conveyed through Fz interaction with atypical cadherin Flamingo (Fmi). More broadly, homophobic signaling may represent a novel mechanism for cell-cell signaling of spatial information through modulation of cell adhesion rather than canonical ligand-receptor binding.

scholarly journals Insect Wing Membrane Topography Is Determined by the Dorsal Wing Epithelium

2013 ◽  
Vol 3 (1) ◽  
pp. 5-8 ◽  
Author(s):  
Andrea D Belalcazar ◽  
Kristy Doyle ◽  
Justin Hogan ◽  
David Neff ◽  
Simon Collier
Keyword(s):  
Planar Cell Polarity ◽  
Parasitic Wasp ◽  
Ventral Surface ◽  
Wing Membrane ◽  
Genetic Studies ◽  
Insect Wing ◽  
Membrane Topography ◽  
Wing Hair ◽  
Pcp Signaling ◽  
Multiple Cells

Abstract The Drosophila wing consists of a transparent wing membrane supported by a network of wing veins. Previously, we have shown that the wing membrane cuticle is not flat but is organized into ridges that are the equivalent of one wing epithelial cell in width and multiple cells in length. These cuticle ridges have an anteroposterior orientation in the anterior wing and a proximodistal orientation in the posterior wing. The precise topography of the wing membrane is remarkable because it is a fusion of two independent cuticle contributions from the dorsal and ventral wing epithelia. Here, through morphological and genetic studies, we show that it is the dorsal wing epithelium that determines wing membrane topography. Specifically, we find that wing hair location and membrane topography are coordinated on the dorsal, but not ventral, surface of the wing. In addition, we find that altering Frizzled Planar Cell Polarity (i.e., Fz PCP) signaling in the dorsal wing epithelium alone changes the membrane topography of both dorsal and ventral wing surfaces. We also examined the wing morphology of two model Hymenopterans, the honeybee Apis mellifera and the parasitic wasp Nasonia vitripennis. In both cases, wing hair location and wing membrane topography are coordinated on the dorsal, but not ventral, wing surface, suggesting that the dorsal wing epithelium also controls wing topography in these species. Because phylogenomic studies have identified the Hymenotera as basal within the Endopterygota family tree, these findings suggest that this is a primitive insect character.

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 SHROOM3 is a novel component of the planar cell polarity pathway whose disruption causes congenital heart disease

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Alison Schmidt ◽  
Matthew Durbin, MS MD ◽  
James O’Kane, MS ◽  
Stephanie M. Ware, MD PHD
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Signaling Pathway ◽  
Cell Polarity ◽  
Congenital Heart ◽  
Planar Cell Polarity ◽  
Cardiac Development ◽  
Genetic Interaction ◽  
Compound Heterozygous ◽  
Pcp Signaling

Congenital heart disease (CHD) is the most common cause of death due to birth defects. Despite CHD frequency, the etiology remains mostly unknown. Understanding CHD genetics and elucidating disease mechanism will help establish prognosis, identify comorbidity risks, and develop targeted therapies. CHD often results from disrupted cytoarchitecture and signaling pathways. We have identified a novel CHD candidate SHROOM3, a protein associated with the actin cytoskeleton and the Wnt/Planar Cell Polarity (PCP) signaling pathway. SHROOM3 induces actomyosin constriction within the apical side of cells and is implicated in neural tube defects and chronic renal failure in humans. A recent study demonstrated that SHROOM3 interacts with Dishevelled2 (DVL2), a component of the PCP signaling pathway, suggesting that SHROOM3 serves as an important link between acto-myosin constriction and PCP signaling. PCP signaling establishes cell polarity required for multiple developmental processes, and is required for cardiac development. In Preliminary data we utilized a Shroom3 gene-trap mouse (Shroom3gt/gt) to demonstrated that SHROOM3 disruption leads to cardiac defects phenocopy PCP disruption. We also demonstrate that patients with CHD phenotypes have rare and potentially damaging SHROOM3 variants within SHROOM3’s PCP-binding domain. We hypothesize SHROOM3 is a novel terminal effector of PCP signaling, and disruption is a novel contributor to CHD. To test this, we assessed genetic interaction between SHROOM3 and PCP during cardiac development and the ultimate effect on cell structure and movement. Heterozygous Shroom3+/gt mice and heterozygous Dvl2 +/- mice are phenotypically normal. We demonstrated genetic interaction between SHROOM3 and PCP signaling by generating compound heterozygous Shroom3+/gt ;Dvl2 +/- mice and identifying a Double Outlet Right Ventricle and Ventricular Septal Defect in one embryo. We also observed fewer compound heterozygous mice than anticipated by Mendelian rations (observed: 18.4%; expected: 25%; n=76), suggesting potential lethality in utero. Immunohistochemistry demonstrates disrupted actomyosin in the SHROOM3gt/gt mice, characteristic of PCP disruption. These data help strengthen SHROOM3 as a novel CHD candidate gene and a component of the PCP Signaling pathway. Further characterization of this gene is important for CHD diagnosis and therapeutic development.

scholarly journals Planar Cell Polarity Signaling Pathway in Congenital Heart Diseases

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Gang Wu ◽  
Jiao Ge ◽  
Xupei Huang ◽  
Yimin Hua ◽  
Dezhi Mu
Keyword(s):  
Signaling Pathway ◽  
Cell Polarity ◽  
Congenital Heart ◽  
Planar Cell Polarity ◽  
Heart Diseases ◽  
Multiple Roles ◽  
Cardiac Differentiation ◽  
Tissue Polarity ◽  
Cardiac Disorder ◽  
Pcp Signaling

Congenital heart disease (CHD) is a common cardiac disorder in humans. Despite many advances in the understanding of CHD and the identification of many associated genes, the fundamental etiology for the majority of cases remains unclear. The planar cell polarity (PCP) signaling pathway, responsible for tissue polarity inDrosophilaand gastrulation movements and cardiogenesis in vertebrates, has been shown to play multiple roles during cardiac differentiation and development. The disrupted function of PCP signaling is connected to some CHDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of CHD.

scholarly journals Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis

Science ◽  
2010 ◽  
Vol 329 (5997) ◽  
pp. 1337-1340 ◽  
Author(s):  
Su Kyoung Kim ◽  
Asako Shindo ◽  
Tae Joo Park ◽  
Edwin C. Oh ◽  
Srimoyee Ghosh ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Control Point ◽  
Cell Movement ◽  
Cytoskeletal Proteins ◽  
Pcp Signaling ◽  
Cellular Machinery ◽  
And Migration ◽  
Controlling Behaviors ◽  
Shed Light

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.

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.

scholarly journals Par3 is essential for the establishment of planar cell polarity of inner ear hair cells

2019 ◽  
Vol 116 (11) ◽  
pp. 4999-5008 ◽  
Author(s):  
Andre Landin Malt ◽  
Zachary Dailey ◽  
Julia Holbrook-Rasmussen ◽  
Yuqiong Zheng ◽  
Arielle Hogan ◽  
...  
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Cell Polarity ◽  
Hair Cells ◽  
Planar Cell Polarity ◽  
Tissue Level ◽  
Hair Bundle ◽  
Nucleotide Exchange ◽  
Genetic Mosaic ◽  
Pcp Signaling

In the inner ear sensory epithelia, stereociliary hair bundles atop sensory hair cells are mechanosensory apparatus with planar polarized structure and orientation. This is established during development by the concerted action of tissue-level, intercellular planar cell polarity (PCP) signaling and a hair cell-intrinsic, microtubule-mediated machinery. However, how various polarity signals are integrated during hair bundle morphogenesis is poorly understood. Here, we show that the conserved cell polarity protein Par3 is essential for planar polarization of hair cells. Par3 deletion in the inner ear disrupted cochlear outgrowth, hair bundle orientation, kinocilium positioning, and basal body planar polarity, accompanied by defects in the organization and cortical attachment of hair cell microtubules. Genetic mosaic analysis revealed that Par3 functions both cell-autonomously and cell-nonautonomously to regulate kinocilium positioning and hair bundle orientation. At the tissue level, intercellular PCP signaling regulates the asymmetric localization of Par3, which in turn maintains the asymmetric localization of the core PCP protein Vangl2. Mechanistically, Par3 interacts with and regulates the localization of Tiam1 and Trio, which are guanine nucleotide exchange factors (GEFs) for Rac, thereby stimulating Rac-Pak signaling. Finally, constitutively active Rac1 rescued the PCP defects in Par3-deficient cochleae. Thus, a Par3–GEF–Rac axis mediates both tissue-level and hair cell-intrinsic PCP signaling.

Nemo-like kinase 1 (Nlk1) and paraxial protocadherin (PAPC) cooperatively control Xenopus gastrulation through regulation of Wnt/planar cell polarity (PCP) signaling

2017 ◽  
Vol 93 ◽  
pp. 27-38 ◽  
Author(s):  
Rahul Kumar ◽  
Anja Ciprianidis ◽  
Susanne Theiß ◽  
Herbert Steinbeißer ◽  
Lilian T. Kaufmann
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Pcp Signaling

scholarly journals STAT3 noncell-autonomously controls planar cell polarity during zebrafish convergence and extension

2004 ◽  
Vol 166 (7) ◽  
pp. 975-981 ◽  
Author(s):  
Chiemi Miyagi ◽  
Susumu Yamashita ◽  
Yusuke Ohba ◽  
Hisayoshi Yoshizaki ◽  
Michiyuki Matsuda ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Cell Polarization ◽  
Rhoa Activity ◽  
Stat3 Signaling ◽  
Convergence And Extension ◽  
Pcp Signaling ◽  
Autonomous Activity ◽  
Rhoa Signaling ◽  
Transcription 3

Zebrafish signal transducer and activator of transcription 3 (STAT3) controls the cell movements during gastrulation. Here, we show that noncell-autonomous activity of STAT3 signaling in gastrula organizer cells controls the polarity of neighboring cells through Dishevelled-RhoA signaling in the Wnt-planar cell polarity (Wnt-PCP) pathway. In STAT3-depleted embryos, although all the known molecules in the Wnt-PCP pathway were expressed normally, the RhoA activity in lateral mesendodermal cells was down-regulated, resulting in severe cell polarization defects in convergence and extension movements identical to Strabismus-depleted embryos. Cell-autonomous activation of Wnt-PCP signaling by ΔN-dishevelled rescued the defect in cell elongation, but not the orientation of lateral mesendodermal cells in STAT3-depleted embryos. The defect in the orientation could be rescued by transplantation of shield cells having noncell-autonomous activity of STAT3 signaling. These results suggest that the cells undergoing convergence and extension movement may sense the gradient of signaling molecules, which are expressed in gastrula organizer by STAT3 and noncell-autonomously activate PCP signaling in neighboring cells during zebrafish gastrulation.

Sign in / Sign up

Export Citation Format

Share Document