Postembryonic Maintenance of Nephron Progenitor Cells with Low Translational Activity in the Chondrichthyan Scyliorhinus canicula

Background: While adult mammals are unable to grow new nephrons, cartilaginous fish kidneys display nephrogenesis throughout life. In this study, we investigated the molecular properties of nephron progenitor cells (NPCs) within the kidney of the catshark ( Scyliorhinus canicula ). Methods: We used branched DNA (bDNA) in situ hybridization to analyze markers expressed in catshark NPCs. BrdU pulse-chase labelling was also performed to test whether NPCs are slow-cycling cells. To question the mechanisms allowing NPC maintenance in the catshark post-embryonic kidney, we measured global protein synthesis rates using in vivo OP-puromycin incorporation. We also investigated the expression of two targets of the mTOR pathway, an important signaling pathway for translation initiation. Results: We found that NPCs express molecular markers previously identified in mice and teleost embryonic NPCs such as the transcription factors Six2, Pax2 and Wt1. At post-embryonic stages, these NPCs are integrated into a specific nephrogenic area of the kidney and contain slow-cycling cells. We also evidenced that NPCs have lower protein synthesis levels than the differentiated cells present in forming nephrons. Such transition from low to high translation rates has been previously observed in several populations of vertebrate stem cells as they undergo differentiation. Finally, we reported the phosphorylation of two targets of the mTOR pathway, p4E-BP1 and pS6K1, in catshark differentiated epithelial cells but not in the NPCs. Conclusions: This first molecular analysis of NPCs in a chondrichthyan species indicates that translation rate increases in NPCs as they differentiate into epithelial cells of the nephron.