ArticleDevelopmental biology2010
The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage.
Article in Developmental biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 83 citations in OpenAlex.
- A knock inbioRxiv : the preprint server for biology · 2026Article
- Transcription factors ETV4 and ETV5 are required for nephron progenitor cell maintenance, distal nephron development and connection to the collecting system.Frontiers in cell and developmental biology · 2026Article
- Kidney and vascular involvement in Alagille syndrome.Pediatric nephrology (Berlin, Germany) · 2025Review
- Generation of proximal tubule-enhanced kidney organoids from human pluripotent stem cells.Nature protocols · 2023Review
- SPOC domain proteins in health and disease.Genes & development · 2023Review
- Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids.Nature communications · 2022Article
- Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids.bioRxiv : the preprint server for biology · 2022Article
- Revisiting the role of Notch in nephron segmentation confirms a role for proximal fate selection during mouse and human nephrogenesis.Development (Cambridge, England) · 2022Article
- Sirt3 promotes the autophagy of HK‑2 human proximal tubular epithelial cells via the inhibition of Notch‑1/Hes‑1 signaling.Molecular medicine reports · 2021Article
- ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling.The Journal of pathology · 2020Article
- Hnf4a Is Required for the Development of Cdh6-Expressing Progenitors into Proximal Tubules in the Mouse Kidney.Journal of the American Society of Nephrology : JASN · 2020Article
- Adaptive response of the murine collecting duct to alkali loading.Pflugers Archiv : European journal of physiology · 2020Article
- Notch signaling regulates Akap12 expression and primary cilia length during renal tubule morphogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Diabetic Nephropathy: Novel Molecular Mechanisms and Therapeutic Targets.Frontiers in pharmacology · 2020Review
- β-catenin regulates the formation of multiple nephron segments in the mouse kidney.Scientific reports · 2019Article
- Notch Signaling in Kidney Development, Maintenance, and Disease.Biomolecules · 2019Review
- Kidney organoids: accurate models or fortunate accidents.Genes & development · 2019Review
- Development of the renal vasculature.Seminars in cell & developmental biology · 2019Review
- A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.Nature communications · 2019Article
- Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney.Development (Cambridge, England) · 2018Article
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7 authors at 3 institutions in 1 country.
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Abstract
We previously determined that Notch2, and not Notch1, was required for forming proximal nephron segments. The dominance of Notch2 may be conserved in humans, since Notch2 mutations occur in Alagille syndrome (ALGS) 2 patients, which includes renal complications. To test whether mutations in Notch1 could increase the severity of renal complications in ALGS, we inactivated conditional Notch1 and Notch2 alleles in mice using a Six2-GFP::Cre. This BAC transgene is expressed mosaically in renal epithelial progenitors but uniformly in cells exiting the progenitor pool to undergo mesenchymal-to-epithelial transition. Although delaying Notch2 inactivation had a marginal effect on nephron numbers, it created a sensitized background in which the inactivation of Notch1 severely compromised nephron formation, function, and survival. These and additional observations indicate that Notch1 in concert with Notch2 contributes to the morphogenesis of renal vesicles into S-shaped bodies in a RBP-J-dependent manner. A significant implication is that elevating Notch1 activity could improve renal functions in ALGS2 patients. As proof of principle, we determined that conditional inactivation of Mint, an inhibitor of Notch-RBP-J interaction, resulted in a moderate rescue of Notch2 null kidneys, implying that temporal blockage of Notch signaling inhibitors downstream of receptor activation may have therapeutic benefits for ALGS patients.
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