R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors
- University of Nice, France
- CNRS, France
- A*STAR, Singapore
Abstract
During kidney development, WNT/b-catenin signalling has to be tightly controlled to ensure proliferation and differentiation of nephron progenitor cells. Here we show in mice that the signalling molecules RSPO1 and RSPO3 act in a functionally redundant manner to permit WNT/b-catenin signalling and their genetic deletion leads to a rapid decline of nephron progenitors. By contrast, tissue specific deletion in cap mesenchymal cells abolishes mesenchyme to epithelial transition (MET) that is linked to a loss of Bmp7 expression, absence of SMAD1/5 phosphorylation and a concomitant failure to activate Lef1, Fgf8 and Wnt4, thus explaining the observed phenotype on a molecular level. Surprisingly, the full knockout of LGR4/5/6, the cognate receptors of R-spondins, only mildly affects progenitor numbers, but does not interfere with MET. Taken together our data demonstrate key roles for R-spondins in permitting stem cell maintenance and differentiation and reveal Lgr-dependent and independent functions for these ligands during kidney formation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.Source data files have been provided for Figures 2B, 2C, 2F, 3C, 3D, 4E, 5D, 5F 6C, Suppl. Figure 1A
Article and author information
Author details
Marie-Christine Chaboissier
Funding
European Commission (305608)
- Andreas Schedl
Ligue Contre le Cancer (Equipe labelisee)
- Andreas Schedl
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Roel Nusse, Stanford University, United States
Ethics
Animal experimentation: The experiments described in this paper were carried out in compliance with the French and international animal welfare laws, guidelines and policies and were approved by the local ethics committee (PEA No NCE-2014-207 and PEA No: 2018060516474844 (V2)).
Version history
- Received: November 23, 2019
- Accepted: April 23, 2020
- Accepted Manuscript published: April 23, 2020 (version 1)
- Accepted Manuscript updated: May 1, 2020 (version 2)
- Version of Record published: May 15, 2020 (version 3)
Copyright
© 2020, Vidal et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors
eLife 9:e53895.
https://doi.org/10.7554/eLife.53895
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