| First Author | Wesselman HM | Year | 2023 |
| Journal | Development | Volume | 150 |
| Issue | 10 | PubMed ID | 37232416 |
| Mgi Jnum | J:336093 | Mgi Id | MGI:7486434 |
| Doi | 10.1242/dev.201411 | Citation | Wesselman HM, et al. (2023) Esrrgammaa regulates nephron and ciliary development by controlling prostaglandin synthesis. Development 150(10) |
| abstractText | Cilia are essential for the ontogeny and function of many tissues, including the kidney. Here, we report that transcription factor ERRgamma ortholog estrogen related receptor gamma a (Esrrgammaa) is essential for renal cell fate choice and ciliogenesis in zebrafish. esrrgammaa deficiency altered proximodistal nephron patterning, decreased the multiciliated cell populace and disrupted ciliogenesis in the nephron, Kupffer's vesicle and otic vesicle. These phenotypes were consistent with interruptions in prostaglandin signaling, and we found that ciliogenesis was rescued by PGE2 or the cyclooxygenase enzyme Ptgs1. Genetic interaction revealed that peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (Ppargc1a), which acts upstream of Ptgs1-mediated prostaglandin synthesis, has a synergistic relationship with Esrrgammaa in the ciliogenic pathway. These ciliopathic phenotypes were also observed in mice lacking renal epithelial cell (REC) ERRgamma, where significantly shorter cilia formed on proximal and distal tubule cells. Decreased cilia length preceded cyst formation in REC-ERRgamma knockout mice, suggesting that ciliary changes occur early during pathogenesis. These data position Esrrgammaa as a novel link between ciliogenesis and nephrogenesis through regulation of prostaglandin signaling and cooperation with Ppargc1a. |
