دورية أكاديمية
R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors
العنوان: | R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors |
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المؤلفون: | Valerie PI Vidal, Fariba Jian-Motamedi, Samah Rekima, Elodie P Gregoire, Emmanuelle Szenker-Ravi, Marc Leushacke, Bruno Reversade, Marie-Christine Chaboissier, Andreas Schedl |
المصدر: | eLife, Vol 9 (2020) |
بيانات النشر: | eLife Sciences Publications Ltd, 2020. |
سنة النشر: | 2020 |
المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
مصطلحات موضوعية: | kidney development, wnt signaling, mesenchyme to epithelial transition, Medicine, Science, Biology (General), QH301-705.5 |
الوصف: | 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2050-084X |
Relation: | https://elifesciences.org/articles/53895; https://doaj.org/toc/2050-084X |
DOI: | 10.7554/eLife.53895 |
URL الوصول: | https://doaj.org/article/f5c84534512c4f88a3f0580471dfb328 |
رقم الأكسشن: | edsdoj.f5c84534512c4f88a3f0580471dfb328 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 2050084X |
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DOI: | 10.7554/eLife.53895 |