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Updated: Dec 23, 2025

Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
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Published on: April 22, 2011

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

Valerie Pi Vidal1, Fariba Jian-Motamedi1, Samah Rekima1

  • 1Université Côte d'Azur, Inserm, CNRS, Institut de Biologie Valrose, Nice, France.

Elife
|April 24, 2020
PubMed

Insights

R-spondins (RSPO1 and RSPO3) are crucial for kidney development, maintaining nephron progenitor cells. Their absence halts kidney formation by blocking essential molecular pathways and cell transitions.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Kidney development relies on precise WNT/β-catenin signaling for nephron progenitor cell proliferation and differentiation.
  • R-spondins (RSPO) are key regulators of WNT signaling pathways.

Purpose of the Study:

  • To investigate the roles of RSPO1 and RSPO3 in mouse kidney development.
  • To elucidate the molecular mechanisms underlying RSPO function in nephrogenesis.

Main Methods:

  • Genetic deletion of RSPO1/RSPO3 and LGR4/5/6 in mouse models.
  • Analysis of nephron progenitor cell populations.
  • Gene expression analysis (Bmp7, Lef1, Fgf8, Wnt4) and SMAD1/5 phosphorylation assessment.

Main Results:

  • RSPO1 and RSPO3 exhibit functional redundancy, essential for maintaining nephron progenitors.
  • Deletion of RSPO1/RSPO3 in cap mesenchyme blocks mesenchyme-to-epithelial transition (MET), downregulating Bmp7 and downstream targets.
  • Complete knockout of LGR4/5/6 receptors has minimal impact on progenitor numbers or MET, suggesting Lgr-independent functions for R-spondins.

Conclusions:

  • R-spondins play critical roles in maintaining stem cell populations and facilitating differentiation during kidney formation.
  • This study reveals both Lgr-dependent and Lgr-independent functions of R-spondins in nephrogenesis.
Keywords:
developmental biologykidney developmentmesenchyme to epithelial transitionmouseregenerative medicinestem cellswnt signaling

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