scholarly journals Planar Cell Polarity Pathway in Kidney Development and Function

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Brittany Rocque ◽  
Elena Torban
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Kidney Development ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Oriented Cell Division ◽  
Cell Structures ◽  
Pcp Signaling ◽  
And Function ◽  
Duct Development

The evolutionarily conserved planar cell polarity (PCP) signaling pathway controls tissue polarity within the plane orthogonal to the apical-basal axis. PCP was originally discovered in Drosophila melanogaster where it is required for the establishment of a uniform pattern of cell structures and appendages. In vertebrates, including mammals, the PCP pathway has been adapted to control various morphogenetic processes that are critical for tissue and organ development. These include convergent extension (crucial for neural tube closure and cochlear duct development) and oriented cell division (needed for tubular elongation), ciliary tilting that enables directional fluid flow, and other processes. Recently, strong evidence has emerged to implicate the PCP pathway in vertebrate kidney development. In this review, we will describe the experimental data revealing the role of PCP signaling in nephrogenesis and kidney disease.

scholarly journals Update on the Role of the Non-Canonical Wnt/Planar Cell Polarity Pathway in Neural Tube Defects

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1198 ◽  
Author(s):  
Wang ◽  
Marco ◽  
Capra ◽  
Kibar
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Complex Genetics ◽  
Pcp Signaling ◽  
Canonical Wnt

Neural tube defects (NTDs), including spina bifida and anencephaly, represent the most severe and common malformations of the central nervous system affecting 0.7–3 per 1000 live births. They result from the failure of neural tube closure during the first few weeks of pregnancy. They have a complex etiology that implicate a large number of genetic and environmental factors that remain largely undetermined. Extensive studies in vertebrate models have strongly implicated the non-canonical Wnt/planar cell polarity (PCP) signaling pathway in the pathogenesis of NTDs. The defects in this pathway lead to a defective convergent extension that is a major morphogenetic process essential for neural tube elongation and subsequent closure. A large number of genetic studies in human NTDs have demonstrated an important role of PCP signaling in their etiology. However, the relative contribution of this pathway to this complex etiology awaits a better picture of the complete genetic architecture of these defects. The emergence of new genome technologies and bioinformatics pipelines, complemented with the powerful tool of animal models for variant interpretation as well as significant collaborative efforts, will help to dissect the complex genetics of NTDs. The ultimate goal is to develop better preventive and counseling strategies for families affected by these devastating conditions.

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 Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure

Development ◽  
2007 ◽  
Vol 134 (4) ◽  
pp. 789-799 ◽  
Author(s):  
P. Ybot-Gonzalez ◽  
D. Savery ◽  
D. Gerrelli ◽  
M. Signore ◽  
C. E. Mitchell ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Planar Cell Polarity ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Tube Closure ◽  
Planar Cell Polarity Signalling

Cardiac growth II: Cardiomyocyte polarization

2018 ◽  
Author(s):  
Stéphane Zaffran
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Heart Diseases ◽  
Neural Crest Cell ◽  
Early Embryo ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Heart Tube ◽  
Heart Morphogenesis ◽  
Cardiac Progenitors

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.

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 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.

Sign in / Sign up

Export Citation Format

Share Document