Progenitor translatome changes coordinated by Tsc1 increase perception of Wnt signals to end nephrogenesis.

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

SUBMITTER: Jarmas AE 

PROVIDER: S-EPMC8566581 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature