TY - JOUR
T1 - R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors
AU - Vidal, Valerie P.I.
AU - Motamedi, Fariba Jian
AU - Rekima, Samah
AU - Gregoire, Elodie P.
AU - Szenker-Ravi, Emmanuelle
AU - Leushacke, Marc
AU - Reversade, Bruno
AU - Chaboissier, Marie Christine
AU - Schedl, Andreas
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
UR - https://elifesciences.org/articles/53895
UR - http://www.scopus.com/inward/record.url?scp=85085037592&partnerID=8YFLogxK
U2 - 10.7554/eLife.53895
DO - 10.7554/eLife.53895
M3 - Article
SN - 2050-084X
VL - 9
JO - eLife
JF - eLife
ER -