ArticleDevelopmental cell2013
The extracellular domain of Notch2 increases its cell-surface abundance and ligand responsiveness during kidney development.
Article in Developmental cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 111 citations in OpenAlex.
- Developmental chronology of mouse embryo from 2-cell stage through birth.Nature cell biology · 2026Article
- Biliary atresia-related liver fibrosis.Frontiers in cell and developmental biology · 2026Review
- Controlling nephron precursor differentiation to generate proximal-biased kidney organoids with emerging maturity.Nature communications · 2025Article
- Axial nephron fate switching demonstrates a plastic system tunable on demand.Nature communications · 2025Article
- Notch2 Inhibition and Kidney Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2025Article
- Kidney and vascular involvement in Alagille syndrome.Pediatric nephrology (Berlin, Germany) · 2025Review
- Article
- Hedgehog signaling is required for the maintenance of mesenchymal nephron progenitors.bioRxiv : the preprint server for biology · 2024Article
- Unraveling paralog-specific Notch signaling through thermodynamics of ternary complex formation and transcriptional activation of chimeric receptors.Protein science : a publication of the Protein Society · 2024Article
- Analysis of Notch1 signaling in mammalian sperm development.BMC research notes · 2023Article
- A topographic atlas defines developmental origins of cell heterogeneity in the human embryonic lung.Nature cell biology · 2023Article
- Recent advances inFrontiers in cell and developmental biology · 2023Review
- Article
- Perivascular cells support folliculogenesis in the developing ovary.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Principles of human and mouse nephron development.Nature reviews. Nephrology · 2022Review
- Disruption of mitochondrial complex III in cap mesenchyme but not in ureteric progenitors results in defective nephrogenesis associated with amino acid deficiency.Kidney international · 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
- Spatial transcriptional mapping of the human nephrogenic program.Developmental cell · 2021Article
- Biophysics of Notch Signaling.Annual review of biophysics · 2021Review
- Current Views on the Roles ofBiomolecules · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Notch2, but not Notch1, plays indispensable roles in kidney organogenesis, and Notch2 haploinsufficiency is associated with Alagille syndrome. We proposed that proximal nephron fates are regulated by a threshold that requires nearly all available free Notch intracellular domains (NICDs) but could not identify the mechanism that explains why Notch2 (N2) is more important than Notch1 (N1). By generating mice that swap their ICDs, we establish that the overall protein concentration, expression domain, or ICD amino acid composition does not account for the differential requirement of these receptors. Instead, we find that the N2 extracellular domain (NECD) increases Notch protein localization to the cell surface during kidney development and is cleaved more efficiently upon ligand binding. This context-specific asymmetry in NICD release efficiency is further enhanced by Fringe. Our results indicate that an elevated N1 surface level could compensate for the loss of N2 signal in specific cell contexts.
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Registered trials
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