ArticleCell2018
Dynamic Ligand Discrimination in the Notch Signaling Pathway.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 1 of them a synthesis that pooled it.
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Who cites it
174 citing papers in PubMed, 1 synthesis or guideline pooled it, 345 citations in OpenAlex.
- Roles of the Notch Signaling Pathway in Ovarian Functioning.Reproductive sciences (Thousand Oaks, Calif.) · 2021Pooled it
- Pan-cancer analysis of Notch pathway-linked gene expression identifies tumour-specific and sex-stratified prognostic associations.Clinical and translational radiation oncology · 2026Article
- Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for high-grade glioma.Oncogene · 2026Article
- Article
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- A multiscale, Bayesian inference approach to augment mechanistic models of cell signaling with machine-learning predictions of binding affinity.PLoS computational biology · 2026Article
- The Blockade of Delta-Like Ligand 1 Inhibits Atherosclerotic Lesion Formation and Attenuates Plaque Vulnerability.Journal of atherosclerosis and thrombosis · 2026Article
- Resolving thyroid lineage cell trajectories merging into a dual endocrine gland in mammals.Nature communications · 2026Article
- Hepatic glutathione depletion ameliorates MASLD through selective protein oxidation and inhibition of lipogenesis.The Journal of clinical investigation · 2026Article
- Insights Into Macrophage Polarization and M1/M2 Balance in Diabetic Foot Ulcers.Journal of diabetes · 2026Review
- Oncogenic Alterations in PI3K Signaling Emulated Optogenetically Recapitulate Some Phenotypic Changes in Mammary Epithelia.ACS synthetic biology · 2026Article
- Tumor-associated macrophages promote chemoresistance to Paclitaxel via activating NOTCH2-JAG1 juxtacrine signaling.Molecular cancer · 2026Article
- Role of Notch signaling pathway in joint homeostasis and osteoarthritis.Frontiers in bioengineering and biotechnology · 2026Review
- Receptor dimerization enables ligand discrimination through tunable response heterogeneity.PLoS computational biology · 2025Article
- E-Cadherin Regulates HIF1-α In Vitro in Induced 3D Spheroid Models of Human Breast Cancer Through Both mTOR and Notch1 Signaling.Biomedicines · 2025Article
- Ligand discrimination in immune cells: Signal processing insights into immune dysfunction in ER+ breast cancer.PLoS computational biology · 2025Article
- The Notch pathway: A guardian of cell fate during neurogenesis.Current opinion in cell biology · 2025Review
- Functional Divergence ofInternational journal of molecular sciences · 2025Article
- Crosstalk between GLTSCR1-deficient endothelial cells and tumour cells promotes colorectal cancer development by activating the Notch pathway.Cell death and differentiation · 2025Article
- Modes of Notch signalling in development and disease.Nature reviews. Molecular cell biology · 2025Review
114 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The Notch signaling pathway comprises multiple ligands that are used in distinct biological contexts. In principle, different ligands could activate distinct target programs in signal-receiving cells, but it is unclear how such ligand discrimination could occur. Here, we show that cells use dynamics to discriminate signaling by the ligands Dll1 and Dll4 through the Notch1 receptor. Quantitative single-cell imaging revealed that Dll1 activates Notch1 in discrete, frequency-modulated pulses that specifically upregulate the Notch target gene Hes1. By contrast, Dll4 activates Notch1 in a sustained, amplitude-modulated manner that predominantly upregulates Hey1 and HeyL. Ectopic expression of Dll1 or Dll4 in chick neural crest produced opposite effects on myogenic differentiation, showing that ligand discrimination can occur in vivo. Finally, analysis of chimeric ligands suggests that ligand-receptor clustering underlies dynamic encoding of ligand identity. The ability of the pathway to utilize ligands as distinct communication channels has implications for diverse Notch-dependent processes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.