ArticleeLife2018
The ectodomains determine ligand function in vivo and selectivity of DLL1 and DLL4 toward NOTCH1 and NOTCH2 in vitro.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Notch Signaling in Spinal Cord Injury: Mechanistic Insights and Therapeutic Perspectives.Molecular neurobiology · 2026Review
- The Blockade of Delta-Like Ligand 1 Inhibits Atherosclerotic Lesion Formation and Attenuates Plaque Vulnerability.Journal of atherosclerosis and thrombosis · 2026Article
- Dimerization-dependent NOTCH receptor transactivation unveils a class of highly selective NOTCH signalling inhibitors.The FEBS journal · 2026Article
- Splenic fibroblasts control marginal zone B cell movement and function via two distinct Notch2-dependent regulatory programs.Immunity · 2025Article
- Article
- Astrogliosis in multiple sclerosis and neuro-inflammation: what role for the notch pathway?Frontiers in immunology · 2023Review
- Dll1 Can Function as a Ligand of Notch1 and Notch2 in the Thymic Epithelium.Frontiers in immunology · 2022Article
- O-Fucose and Fringe-modified NOTCH1 extracellular domain fragments as decoys to release niche-lodged hematopoietic progenitor cells.Glycobiology · 2021Article
- Biophysics of Notch Signaling.Annual review of biophysics · 2021Review
- Review
- Oscillations of Delta-like1 regulate the balance between differentiation and maintenance of muscle stem cells.Nature communications · 2021Article
- Current Views on the Roles ofBiomolecules · 2021Review
- Review
- Canonical Notch ligands and Fringes have distinct effects on NOTCH1 and NOTCH2.The Journal of biological chemistry · 2020Article
- Reciprocal communication between astrocytes and endothelial cells is required for astrocytic glutamate transporter 1 (GLT-1) expression.Neurochemistry international · 2020Article
- Article
- Vascular Notch Signaling in Stress Hematopoiesis.Frontiers in cell and developmental biology · 2020Review
- Notch in the niche: new insights into the role of Notch signaling in the bone marrow.Haematologica · 2019Article
- NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells.The Journal of biological chemistry · 2019Article
- Notch and Wnt Dysregulation and Its Relevance for Breast Cancer and Tumor Initiation.Biomedicines · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
DLL1 and DLL4 are Notch ligands with high structural similarity but context-dependent functional differences. Here, we analyze their functional divergence using cellular co-culture assays, biochemical studies, and in vivo experiments. DLL1 and DLL4 activate NOTCH1 and NOTCH2 differently in cell-based assays and this discriminating potential lies in the region between the N-terminus and EGF repeat three. Mice expressing chimeric ligands indicate that the ectodomains dictate ligand function during somitogenesis, and that during myogenesis even regions C-terminal to EGF3 are interchangeable. Substitution of NOTCH1-interface residues in the MNNL and DSL domains of DLL1 with the corresponding amino acids of DLL4, however, does not disrupt DLL1 function in vivo. Collectively, our data show that DLL4 preferentially activates NOTCH1 over NOTCH2, whereas DLL1 is equally effective in activating NOTCH1 and NOTCH2, establishing that the ectodomains dictate selective ligand function in vivo, and that features outside the known binding interface contribute to their differences.
Indexed as
Identifiers
What OpenQuestion holds
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.