ArticlePloS one2016
Wnt5a Deficiency Leads to Anomalies in Ureteric Tree Development, Tubular Epithelial Cell Organization and Basement Membrane Integrity Pointing to a Role in Kidney Collecting Duct Patterning.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 34 citations in OpenAlex.
- Integration of spatial and single-nucleus transcriptomics to map gene expression in the developing mouse kidney.Development (Cambridge, England) · 2025Article
- The life cycle of type IV collagen.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- A homozygous human WNT11 variant is associated with laterality, heart and renal defects.Disease models & mechanisms · 2025Article
- Wnt/β-Catenin Signaling and Congenital Abnormalities of Kidney and Urinary Tract.Kidney diseases (Basel, Switzerland) · 2024Review
- Overexpression of long noncoding RNAFrontiers in cell and developmental biology · 2023Article
- 3D Mapping Reveals a Complex and Transient Interstitial Matrix During Murine Kidney Development.Journal of the American Society of Nephrology : JASN · 2021Article
- Planar cell polarity pathway in kidney development, function and disease.Nature reviews. Nephrology · 2021Review
- MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus.Development (Cambridge, England) · 2021Article
- Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.Journal of the American Society of Nephrology : JASN · 2021Article
- The Biological Significance and Implications of Planar Cell Polarity for Nephrology.Frontiers in physiology · 2021Review
- Wnt signaling in kidney: the initiator or terminator?Journal of molecular medicine (Berlin, Germany) · 2020Review
- Mutational analysis of genes with ureteric progenitor cell-specific expression in branching morphogenesis of the mouse kidney.Developmental dynamics : an official publication of the American Association of Anatomists · 2020Article
- Morphogenesis of the kidney and lung requires branch-tip directed activity of the Adamts18 metalloprotease.Developmental biology · 2019Article
- COL4A1 mutations as a potential novel cause of autosomal dominant CAKUT in humans.Human genetics · 2019Article
- Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney.Development (Cambridge, England) · 2018Article
- Reduced Abd-B Hox function during kidney development results in lineage infidelity.Developmental biology · 2018Article
- Wnt Signaling in Kidney Development and Disease.Progress in molecular biology and translational science · 2018Review
- Wnt Signaling in Renal Cell Carcinoma.Cancers · 2016Review
- Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.Differentiation; research in biological diversityArticle
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Authors and funding
15 authors at 3 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
The Wnts can be considered as candidates for the Congenital Anomaly of Kidney and Urinary Tract, CAKUT diseases since they take part in the control of kidney organogenesis. Of them Wnt5a is expressed in ureteric bud (UB) and its deficiency leads to duplex collecting system (13/90) uni- or bilateral kidney agenesis (10/90), hypoplasia with altered pattern of ureteric tree organization (42/90) and lobularization defects with partly fused ureter trunks (25/90) unlike in controls. The UB had also notably less tips due to Wnt5a deficiency being at E15.5 306 and at E16.5 765 corresponding to 428 and 1022 in control (p<0.02; p<0.03) respectively. These changes due to Wnt5a knock out associated with anomalies in the ultrastructure of the UB daughter epithelial cells. The basement membrane (BM) was malformed so that the BM thickness increased from 46.3 nm to 71.2 nm (p<0.01) at E16.5 in the Wnt5a knock out when compared to control. Expression of a panel of BM components such as laminin and of type IV collagen was also reduced due to the Wnt5a knock out. The P4ha1 gene that encodes a catalytic subunit of collagen prolyl 4-hydroxylase I (C-P4H-I) in collagen synthesis expression and the overall C-P4H enzyme activity were elevated by around 26% due to impairment in Wnt5a function from control. The compound Wnt5a+/-;P4ha1+/- embryos demonstrated Wnt5a-/- related defects, for example local hyperplasia in the UB tree. A R260H WNT5A variant was identified from renal human disease cohort. Functional studies of the consequence of the corresponding mouse variant in comparison to normal ligand reduced Wnt5a-signalling in vitro. Together Wnt5a has a novel function in kidney organogenesis by contributing to patterning of UB derived collecting duct development contributing putatively to congenital disease.
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