University of Oulu

Pietilä I, Prunskaite-Hyyryläinen R, Kaisto S, Tika E, van Eerde AM, Salo AM, et al. (2016) 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. PLoS ONE 11(1): e0147171.

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

Saved in:
Author: Pietilä, Ilkka1; Prunskaite-Hyyryläinen, Renata1; Kaisto, Susanna1;
Organizations: 1Laboratory of Developmental Biology, Oulu Centre for Cell-Matrix Research, Biocenter Oulu and Infotech Oulu, and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
2Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
3Oulu Centre for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
4Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
5Biocenter Oulu, University of Oulu, Oulu, Finland
6Department of Urology, Radboudumc Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
7Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.3 MB)
Persistent link:
Language: English
Published: Public Library of Science, 2016
Publish Date: 2020-05-08


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.

see all

Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 11
Issue: 1
Article number: e0147171
DOI: 10.1371/journal.pone.0147171
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by the Academy of Finland (206038, 121647, 250900 and 260056), Centre of Excellence grant 2012–2017 of the Academy of Finland (251314), [] to SV; the Sigrid Jusélius Foundation, [] to SV; the European Community’s Seventh Framework Program FP7/2009 under grant agreement 305608 (EURenOmics: European Consortium for High-Throughput Research in Rare Kidney Diseases) [] to SV and NK; the Dutch Kidney Foundation (KSTP10.004, KSTP12.010, and CP11.18) [] to NK; and Fonds NutsOhra (1303-070) [] to NK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Academy of Finland Grant Number: 206038
Detailed Information: 206038 (Academy of Finland Funding decision)
121647 (Academy of Finland Funding decision)
250900 (Academy of Finland Funding decision)
260056 (Academy of Finland Funding decision)
251314 (Academy of Finland Funding decision)
Copyright information: © 2016 Pietilä et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.