| First Author | Lamontagne JO | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 2226 |
| PubMed ID | 35468900 | Mgi Jnum | J:351393 |
| Mgi Id | MGI:7265920 | Doi | 10.1038/s41467-022-29644-3 |
| Citation | Lamontagne JO, et al. (2022) Transcription factors AP-2alpha and AP-2beta regulate distinct segments of the distal nephron in the mammalian kidney. Nat Commun 13(1):2226 |
| abstractText | Transcription factors AP-2alpha and AP-2beta have been suggested to regulate the differentiation of nephron precursor populations towards distal nephron segments. Here, we show that in the adult mammalian kidney AP-2alpha is found in medullary collecting ducts, whereas AP-2beta is found in distal nephron segments except for medullary collecting ducts. Inactivation of AP-2alpha in nephron progenitor cells does not affect mammalian nephrogenesis, whereas its inactivation in collecting ducts leads to defects in medullary collecting ducts in the adult. Heterozygosity for AP-2beta in nephron progenitor cells leads to progressive distal convoluted tubule abnormalities and beta-catenin/mTOR hyperactivation that is associated with renal fibrosis and cysts. Complete loss of AP-2beta in nephron progenitor cells caused an absence of distal convoluted tubules, renal cysts, and fibrosis with beta-catenin/mTOR hyperactivation, and early postnatal death. Thus, AP-2alpha and AP-2beta have non-redundant distinct spatiotemporal functions in separate segments of the distal nephron in the mammalian kidney. |
