Hamartin regulates cessation of mouse nephrogenesis independently of Mtor

Oded Volovelsky, Thi Nguyen, Alison E. Jarmas, Alexander N. Combes, Sean B. Wilson, Melissa H. Little, David P. Witte, Eric W. Brunskill, Raphael Kopan
2018 Proceedings of the National Academy of Sciences of the United States of America  
Nephrogenesis concludes by the 36th week of gestation in humans and by the third day of postnatal life in mice. Extending the nephrogenic period may reduce the onset of adult renal and cardiovascular disease associated with low nephron numbers. We conditionally deleted either Mtor or Tsc1 (coding for hamartin, an inhibitor of Mtor) in renal progenitor cells. Loss of one Mtor allele caused a reduction in nephron numbers; complete deletion led to severe paucity of glomeruli in the kidney
more » ... in early death after birth. By contrast, loss of one Tsc1 allele from renal progenitors resulted in a 25% increase in nephron endowment with no adverse effects. Increased progenitor engraftment rates ex vivo relative to controls correlated with prolonged nephrogenesis through the fourth postnatal day. Complete loss of both Tsc1 alleles in renal progenitors led to a lethal tubular lesion. The hamartin phenotypes are not dependent on the inhibitory effect of TSC on the Mtor complex but are dependent on Raptor. kidney development | metanephric mesenchyme | Mtor | nephron progenitor cells | Tsc1
doi:10.1073/pnas.1712955115 pmid:29784808 fatcat:2z6ice4yjzbdldx24qouqga3hm