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Article Dans Une Revue eLife Année : 2020

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

Valerie Pi Vidal
  • Fonction : Auteur
Fariba Jian-Motamedi
  • Fonction : Auteur
Samah Rekima
  • Fonction : Auteur
Elodie P Gregoire
  • Fonction : Auteur
Emmanuelle Szenker-Ravi
  • Fonction : Auteur
Marc Leushacke
  • Fonction : Auteur
Bruno Reversade
Andreas Schedl

Résumé

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.
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Dates et versions

hal-02992461 , version 1 (06-11-2020)

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Valerie Pi Vidal, Fariba Jian-Motamedi, Samah Rekima, Elodie P Gregoire, Emmanuelle Szenker-Ravi, et al.. R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors. eLife, 2020, 9, ⟨10.7554/elife.53895⟩. ⟨hal-02992461⟩
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