Related Experiment Video
Updated: Oct 14, 2025
The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions
Published on: February 16, 2017
Progenitor translatome changes coordinated by Tsc1 increase perception of Wnt signals to end nephrogenesis
Alison E Jarmas1,2, Eric W Brunskill1,2, Praneet Chaturvedi1,2
1Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Abstract:
Mammalian nephron endowment is determined by the coordinated cessation of nephrogenesis in independent niches. Here we report that translatome analysis in Tsc1+/- nephron progenitor cells from mice with elevated nephron numbers reveals how differential translation of Wnt antagonists over agonists tips the balance between self-renewal and differentiation. Wnt agonists are poorly translated in young niches, resulting in an environment with low R-spondin and high Fgf20 promoting self-renewal. In older niches we find increased translation of Wnt agonists, including R-spondin and the signalosome-promoting Tmem59, and low Fgf20, promoting differentiation. This suggests that the tipping point for nephron progenitor exit from the niche is controlled by the gradual increase in stability and possibly clustering of Wnt/Fzd complexes in individual cells, enhancing the response to ureteric bud-derived Wnt9b inputs and driving synchronized differentiation. As predicted by these findings, removing one Rspo3 allele in nephron progenitors delays cessation and increases nephron numbers in vivo.
Insights
Nephron endowment relies on coordinated nephrogenesis cessation. Differential translation of Wnt signaling molecules in progenitor cells controls self-renewal versus differentiation, impacting kidney development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Nephrology
Background:
- Mammalian nephron number is established during development through precise regulation of nephrogenesis.
- Nephron progenitor cells reside in distinct niches where their self-renewal and differentiation are tightly controlled.
Purpose of the Study:
- To investigate the role of differential translation in regulating nephron progenitor cell fate.
- To understand how Wnt signaling dynamics influence nephron endowment.
Main Methods:
- Translatome analysis of Tsc1+/- mouse nephron progenitor cells.
- In vivo genetic manipulation to assess the impact of Rspo3 on nephron number.
Main Results:
- Differential translation of Wnt antagonists versus agonists was observed in nephron progenitor niches.
- Younger niches showed poor Wnt agonist translation, favoring self-renewal (low R-spondin, high Fgf20).
- Older niches exhibited increased Wnt agonist translation, promoting differentiation (high R-spondin, low Fgf20).
Conclusions:
- The balance between nephron progenitor self-renewal and differentiation is regulated by translational control of Wnt signaling components.
- Increased stability and clustering of Wnt/Fzd complexes enhance responsiveness to Wnt9b, driving synchronized differentiation.
- Modulating Rspo3 levels in progenitors affects nephron cessation and final nephron count in vivo.
Related Concept Videos
02:54Canonical Wnt Signaling Pathway
01:41Non-Canonical Wnt Signaling Pathways
01:16TGF - β Signaling Pathway
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:51Determination
01:24Regulation of Angiogenesis and Blood Supply