scholarly journals The Biological Significance and Implications of Planar Cell Polarity for Nephrology

2021 ◽  
Vol 12 ◽  
Author(s):  
Eugenia Papakrivopoulou ◽  
Daniyal J. Jafree ◽  
Charlotte H. Dean ◽  
David A. Long
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Kidney Development ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Biological Significance ◽  
Renal Diseases ◽  
Glomerular Diseases ◽  
Treatment Paradigm ◽  
New Treatment

The orientation of cells in two-dimensional and three-dimensional space underpins how the kidney develops and responds to disease. The process by which cells orientate themselves within the plane of a tissue is termed planar cell polarity. In this Review, we discuss how planar cell polarity and the proteins that underpin it govern kidney organogenesis and pathology. The importance of planar cell polarity and its constituent proteins in multiple facets of kidney development is emphasised, including ureteric bud branching, tubular morphogenesis and nephron maturation. An overview is given of the relevance of planar cell polarity and its proteins for inherited human renal diseases, including congenital malformations with unknown aetiology and polycystic kidney disease. Finally, recent work is described outlining the influence of planar cell polarity proteins on glomerular diseases and highlight how this fundamental pathway could yield a new treatment paradigm for nephrology.

scholarly journals Planar cell polarity in kidney development and disease

Organogenesis ◽  
2011 ◽  
Vol 7 (3) ◽  
pp. 180-190 ◽  
Author(s):  
Thomas J. Carroll ◽  
Amrita Das
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Kidney Development

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 Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity–signaling pathway

2016 ◽  
Vol 27 (6) ◽  
pp. 941-953 ◽  
Author(s):  
Aude Guillabert-Gourgues ◽  
Beatrice Jaspard-Vinassa ◽  
Marie-Lise Bats ◽  
Raj N. Sewduth ◽  
Nathalie Franzl ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Cell Structure ◽  
Ectopic Expression ◽  
Three Dimensional ◽  
Cell Polarization ◽  
Directional Migration ◽  
Angiogenesis Assay

Angiogenesis involves the coordinated growth and migration of endothelial cells (ECs) toward a proangiogenic signal. The Wnt planar cell polarity (PCP) pathway, through the recruitment of Dishevelled (Dvl) and Dvl-associated activator of morphogenesis (Daam1), has been proposed to regulate cell actin cytoskeleton and microtubule (MT) reorganization for oriented cell migration. Here we report that Kif26b—a kinesin—and Daam1 cooperatively regulate initiation of EC sprouting and directional migration via MT reorganization. First, we find that Kif26b is recruited within the Dvl3/Daam1 complex. Using a three-dimensional in vitro angiogenesis assay, we show that Kif26b and Daam1 depletion impairs tip cell polarization and destabilizes extended vascular processes. Kif26b depletion specifically alters EC directional migration and mislocalized MT organizing center (MTOC)/Golgi and myosin IIB cell rear enrichment. Therefore the cell fails to establish a proper front–rear polarity. Of interest, Kif26b ectopic expression rescues the siDaam1 polarization defect phenotype. Finally, we show that Kif26b functions in MT stabilization, which is indispensable for asymmetrical cell structure reorganization. These data demonstrate that Kif26b, together with Dvl3/Daam1, initiates cell polarity through the control of PCP signaling pathway–dependent activation.

scholarly journals WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging

2019 ◽  
Vol 44 (2) ◽  
pp. 200-210 ◽  
Author(s):  
Jolanta Kiewisz ◽  
Agnieszka Skowronska ◽  
Agata Winiarska ◽  
Anna Pawlowska ◽  
Jacek Kiezun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Focal Segmental Glomerulosclerosis ◽  
Kidney Development ◽  
Renal Diseases ◽  
Plasma Sodium ◽  
Mrna Levels ◽  
Glomerular Diseases ◽  
Segmental Glomerulosclerosis ◽  
Renal Biopsies ◽  
Wnt4 Gene

Background/Aims: WNT4 protein is important for kidney development. Its expression was found to be altered in experimental models of chronic kidney disease (CKD). However, the expression of the WNT4 gene has yet not been studied in human renal biopsy samples from patients with broad spectrum of glomerular disease and at different stages of CKD. Thus, the aim of the study was to assess the WNT4 gene expression in renal biopsies of 98 patients using the real-time PCR technique. Materials: In order to assess the relative amounts of mRNA, in samples of patients with manifestation of different renal diseases and separately at different stages of CKD, by QPCR, total RNA was isolated from human kidney tissues collected during renal biopsies. Results of blood and urine samples assessment were used to calculate the correlations of biochemical parameters with WNT4 gene expression in both studied groups. Results: After pathomorphological evaluation, 49 patients were selected as presenting the most common cases in the studied group. Among the patients who developed focal segmental glomerulosclerosis (FSGS; n = 13), IgA nephropathy (IgAN; n = 10), IgAN with morphological presentation of focal segmental glomerulosclerosis (IgAN/FSGS; n = 8), membranous nephropathy (MN; n = 12), and lupus nephritis (LN; n = 6) were included in the analysis. We found that the level of WNT4 mRNA was higher in kidney specimens obtained from patients with MN as compared to those diagnosed with LN or IgAN. A correlation between WNT4 gene expression and serum albumin and cholesterol levels was observed in patients with FSGS, while WNT4 mRNA levels correlated with plasma sodium in patients diagnosed with LN. After consideration of 98 patients, based on the KDIGO classification of CKD, 20 patients were classified as CKD1 stage, 23 as stage 2, 13 as stage 3a, 11 as stage 3b, 13 as stage 4, and 18 as stage 5. WNT4 gene expression was lower in the CKD patients in stage 2 as compared to CKD 3a. Correlations of WNT4 mRNA level at different stages of CKD with indices of kidney function and lipid metabolism such as serum levels of HDL and LDL cholesterol, TG, urea, creatinine, sodium, and potassium were also found. Conclusions: Our results suggest that altered WNT4 gene expression in patients with different types of glomerular diseases and patients at different stages of CKD may play a role in kidney tissue disorganization as well as disease development and progression.

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.

Three Dimensional structure and organization of diploid chromosomes by optical section microscopy

1987 ◽  
Vol 45 ◽  
pp. 633-635
Author(s):  
David A. Agard ◽  
Yasushi Hiraoka ◽  
John W. Sedat
Keyword(s):  
Dimensional Space ◽  
Three Dimensional ◽  
Developmental State ◽  
Mitotic Cell ◽  
Biological Properties ◽  
Dimensional Structure ◽  
Specific Gene ◽  
Three Dimensional Structure ◽  
Complementary Techniques ◽  
Dynamic Structures

In an effort to understand the complex relationship between structure and biological function within the nucleus, we have embarked on a program to examine the three-dimensional structure and organization of Drosophila melanogaster embryonic chromosomes. Our overall goal is to determine how DNA and proteins are organized into complex and highly dynamic structures (chromosomes) and how these chromosomes are arranged in three dimensional space within the cell nucleus. Futher, we hope to be able to correlate structual data with such fundamental biological properties as stage in the mitotic cell cycle, developmental state and transcription at specific gene loci.Towards this end, we have been developing methodologies for the three-dimensional analysis of non-crystalline biological specimens using optical and electron microscopy. We feel that the combination of these two complementary techniques allows an unprecedented look at the structural organization of cellular components ranging in size from 100A to 100 microns.

Diffraction contrast of dislocations in icosahedral quasicrystals

1990 ◽  
Vol 48 (4) ◽  
pp. 454-455
Author(s):  
K. Urban ◽  
Z. Zhang ◽  
M. Wollgarten ◽  
D. Gratias
Keyword(s):  
Dimensional Space ◽  
Three Dimensional ◽  
Complete Characterization ◽  
Extinction Condition ◽  
Burgers Vector ◽  
Diffraction Contrast ◽  
Lattice Geometry ◽  
Reference Space ◽  
Icosahedral Quasicrystals ◽  
The One

Recently dislocations have been observed by electron microscopy in the icosahedral quasicrystalline (IQ) phase of Al65Cu20Fe15. These dislocations exhibit diffraction contrast similar to that known for dislocations in conventional crystals. The contrast becomes extinct for certain diffraction vectors g. In the following the basis of electron diffraction contrast of dislocations in the IQ phase is described. Taking account of the six-dimensional nature of the Burgers vector a “strong” and a “weak” extinction condition are found.Dislocations in quasicrystals canot be described on the basis of simple shear or insertion of a lattice plane only. In order to achieve a complete characterization of these dislocations it is advantageous to make use of the one to one correspondence of the lattice geometry in our three-dimensional space (R3) and that in the six-dimensional reference space (R6) where full periodicity is recovered . Therefore the contrast extinction condition has to be written as gpbp + gobo = 0 (1). The diffraction vector g and the Burgers vector b decompose into two vectors gp, bp and go, bo in, respectively, the physical and the orthogonal three-dimensional sub-spaces of R6.

Flavin radicals, conformational sampling and robust design principles in interprotein electron transfer: the trimethylamine dehydrogenase-electron-transferring flavoprotein complex

2004 ◽  
Vol 71 ◽  
pp. 1-14
Author(s):  
David Leys ◽  
Jaswir Basran ◽  
François Talfournier ◽  
Kamaldeep K. Chohan ◽  
Andrew W. Munro ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Kinetic Studies ◽  
Molecular Assembly ◽  
Conformational Sampling ◽  
Trimethylamine Dehydrogenase ◽  
Key Residues ◽  
Electron Transferring Flavoprotein ◽  
Electron Transfer Complex

TMADH (trimethylamine dehydrogenase) is a complex iron-sulphur flavoprotein that forms a soluble electron-transfer complex with ETF (electron-transferring flavoprotein). The mechanism of electron transfer between TMADH and ETF has been studied using stopped-flow kinetic and mutagenesis methods, and more recently by X-ray crystallography. Potentiometric methods have also been used to identify key residues involved in the stabilization of the flavin radical semiquinone species in ETF. These studies have demonstrated a key role for 'conformational sampling' in the electron-transfer complex, facilitated by two-site contact of ETF with TMADH. Exploration of three-dimensional space in the complex allows the FAD of ETF to find conformations compatible with enhanced electronic coupling with the 4Fe-4S centre of TMADH. This mechanism of electron transfer provides for a more robust and accessible design principle for interprotein electron transfer compared with simpler models that invoke the collision of redox partners followed by electron transfer. The structure of the TMADH-ETF complex confirms the role of key residues in electron transfer and molecular assembly, originally suggested from detailed kinetic studies in wild-type and mutant complexes, and from molecular modelling.

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