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.

Planar cell polarity pathway regulates actin rearrangement, cell shape, motility, and nephrin distribution in podocytes

2011 ◽  
Vol 300 (2) ◽  
pp. F549-F560 ◽  
Author(s):  
Sima Babayeva ◽  
Yulia Zilber ◽  
Elena Torban
Keyword(s):  
Cell Motility ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Cell Movement ◽  
Stress Fibers ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Filtration Barrier ◽  
Pcp Signaling ◽  
Cytoskeleton Dynamics

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.

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 A mesoderm-independent role for Nodal signaling in convergence & extension gastrulation movements

2019 ◽  
Author(s):  
Margot L.K. Williams ◽  
Lilianna Solnica-Krezel
Keyword(s):  
Cell Fate ◽  
Planar Cell Polarity ◽  
Cell Polarization ◽  
Nodal Signaling ◽  
Embryonic Patterning ◽  
Embryonic Axes ◽  
Pcp Signaling ◽  
A Cell ◽  
Cellular Machinery ◽  
Axis Extension

ABSTRACTDuring embryogenesis, the distinct morphogenetic cell behavior programs that shape tissues are influenced both by the fate of cells and their position with respect to the embryonic axes, making embryonic patterning a prerequisite for morphogenesis. These two essential processes must therefore be coordinated in space and time to ensure proper development, but mechanisms by which patterning information is translated to the cellular machinery that drives morphogenesis remain poorly understood. Here, we address the role of Nodal morphogen signaling at the intersection of cell fate specification, patterning, and anteroposterior (AP) axis extension in zebrafish gastrulae and embryonic explants. AP axis extension is impaired in Nodal-deficient embryos, but it is unclear whether this defect is strictly secondary to their severe mesendoderm deficiencies or also results from loss of Nodal signaling per se. We find that convergence & extension (C&E) gastrulation movements and underlying mediolateral (ML) cell polarization are reduced in the neuroectoderm of Nodal-deficient mutants and exacerbated by simultaneous disruption of Planar Cell Polarity (PCP) signaling, demonstrating at least partially parallel functions of Nodal and PCP. ML polarity of mutant neuroectoderm cells is not fully restored upon transplantation into wild-type gastrulae, demonstrating a cell autonomous, mesoderm-independent role for Nodal in neural cell polarization. This is further demonstrated by the ability of Nodal ligands to promote neuroectoderm-driven C&E of naïve blastoderm explants in a tissue-autonomous fashion. Finally, temporal manipulation of signaling reveals that Nodal contributes to neural C&E in explants after mesoderm is specified and promotes C&E even in the absence of mesoderm. Together these results reveal a mesoderm-independent, cell-autonomous role for Nodal signaling in neural C&E that may cooperate with previously-described mesoderm-dependent mechanisms to drive AP embryonic axis extension.

scholarly journals Integrins are required for synchronous ommatidial rotation in the Drosophila eye linking planar cell polarity signalling to the extracellular matrix

Open Biology ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 190148 ◽  
Author(s):  
Maria Thuveson ◽  
Konstantin Gaengel ◽  
Giovanna M. Collu ◽  
Mei-ling Chin ◽  
Jaskirat Singh ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Rho Kinase ◽  
Cell Movement ◽  
Interaction Network ◽  
Loss Of Function ◽  
Ommatidial Rotation ◽  
Cytoskeletal Elements ◽  
Function Activity

Integrins mediate the anchorage between cells and their environment, the extracellular matrix (ECM), and form transmembrane links between the ECM and the cytoskeleton, a conserved feature throughout development and morphogenesis of epithelial organs. Here, we demonstrate that integrins and components of the ECM are required during the planar cell polarity (PCP) signalling-regulated cell movement of ommatidial rotation in the Drosophila eye. The loss-of-function mutations of integrins or ECM components cause defects in rotation, with mutant clusters rotating asynchronously compared to wild-type clusters. Initially, mutant clusters tend to rotate faster, and at later stages they fail to be synchronous with their neighbours, leading to aberrant rotation angles and resulting in a disorganized ommatidial arrangement in adult eyes. We further demonstrate that integrin localization changes dynamically during the rotation process. Our data suggest that core Frizzled/PCP factors, acting through RhoA and Rho kinase, regulate the function/activity of integrins and that integrins thus contribute to the complex interaction network of PCP signalling, cell adhesion and cytoskeletal elements required for a precise and synchronous 90° rotation movement.

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 Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination

Oncogene ◽  
2017 ◽  
Vol 36 (36) ◽  
pp. 5158-5167 ◽  
Author(s):  
J H Wald ◽  
J Hatakeyama ◽  
I Printsev ◽  
A Cuevas ◽  
W H D Fry ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
And Migration
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