Developmental and Cell Fate Analyses Support a Postnatal Origin for the Cortical Collecting System in the Mouse Kidney

Key Points An adult-like corticomedullary organization underlying kidney function is established 10 days after birth in the mouse kidney. Genetic lineage tracing demonstrates the cortical collecting duct network is generated from progenitors after birth. Mature cell types of the nephron progenitor–derived connecting tubule and ureteric progenitor–derived collecting epithelium are established by P15. Background Structure and function in the mammalian kidney are organized along a radial axis highlighted by the corticomedullary organization and regional patterning of the collecting system. The arborized collecting epithelium arises through controlled growth, branching, and commitment of Wnt11 + ureteric progenitor cells within cortically localized branch tips until postnatal day 3. Methods We applied in situ hybridization and immunofluorescence to key markers of collecting duct cell types to examine their distribution in the embryonic and postnatal mouse kidneys. To address the contribution of ureteric progenitor cells at a given time to cell diversity and spatial organization in the adult mouse kidney, we performed genetic lineage tracing of Wnt11 + cells in the embryonic and early postnatal mouse kidney. Results Cell fate analyses showed much of the cortical collecting duct network was established postnatally. Furthermore, epithelial reorganization, regional differentiation, and functional maturation of key cell types to an adult-like collecting epithelium was not complete until around 2 weeks after birth in both ureteric progenitor cell–derived collecting system and structurally homologous nephron progenitor cell–derived connecting tubule. Conclusions These studies underline the importance of the relatively understudied early postnatal period to the development of a functional mammalian kidney.