| First Author | Day K | Year | 2026 |
| Journal | Front Cell Dev Biol | Volume | 14 |
| Pages | 1820140 | PubMed ID | 42459831 |
| Mgi Jnum | J:389509 | Mgi Id | MGI:8387061 |
| Doi | 10.3389/fcell.2026.1820140 | Citation | Day K, et al. (2026) Transcription factors ETV4 and ETV5 are required for nephron progenitor cell maintenance, distal nephron development and connection to the collecting system. Front Cell Dev Biol 14:1820140 |
| abstractText | The functional unit of the kidney, the nephron, is composed of the renal corpuscle and the renal tubule that includes proximal tubule, loop of Henle, distal and connecting tubule. Each of these segments perform distinct and complementary roles to ensure body homeostasis and urine excretion into the renal collecting system. During nephrogenesis, nephron progenitor cells (NPCs) either self-renew to maintain the progenitor pool or condense and epithelialize into nascent nephrons. Two transcription factors, ETV4 and ETV5 are downstream targets of receptor tyrosine kinase signaling and are known to act redundantly to drive development of the renal collecting system, but their possible role in nephrogenesis has not been elucidated. Here, we show that Etv4 and Etv5 are expressed in NPCs and developing nephrons. Ablation of Etv5 from NPCs in an Etv4 null background results in hypoplastic kidneys, ectopic NPC differentiation, premature NPC depletion and a severely cystic phenotype. The majority of cysts in these mutants originate from the S3 proximal tubule segment; however, removing Etv4 and Etv5 from the proximal developing nephron was insufficient to recapitulate the cystic phenotype. Further analysis of the NPC double mutant kidneys revealed a significant decrease in distal nephron markers and failure to connect to the collecting duct system in mutant embryonic kidney explants. These findings reveal novel roles for ETV4 and ETV5 in nephrogenesis, from progenitor maintenance to nephron segmentation. |
