R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors

Valerie P.I. Vidal, Fariba Jian Motamedi, Samah Rekima, Elodie P. Gregoire, Emmanuelle Szenker-Ravi, Marc Leushacke, Bruno Reversade, Marie Christine Chaboissier, Andreas Schedl

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

During kidney development, WNT/β-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/β-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.
Original languageEnglish (US)
JournaleLife
Volume9
DOIs
StatePublished - Apr 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine
  • General Immunology and Microbiology
  • General Neuroscience

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