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

التفاصيل البيبلوغرافية
العنوان: R-spondin signalling is essential for the maintenance and differentiation of mouse nephron progenitors
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
الوصف
تدمد:2050084X
DOI:10.7554/eLife.53895