ArticleProceedings of the National Academy of Sciences of the United States of America2015
Jagged-Delta asymmetry in Notch signaling can give rise to a Sender/Receiver hybrid phenotype.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Functional Gene Expression Differentiation of the Notch Signaling Pathway in Female Reproductive Tract Tissues-A Comprehensive Review With Analysis.Frontiers in cell and developmental biology · 2020Pooled it
- Spatial modelling of NOTCH signalling predicts tuneable dynamic heterogeneity in endothelia.NPJ systems biology and applications · 2026Article
- Angiocrine factors in tumor microenvironment: bidirectional crosstalk, mechanistic insights, and therapeutic strategies.Journal of translational medicine · 2026Review
- Targeting stiffness-dependent YAP/TAZ restores angiogenesis dynamics impaired by ALK1 knockout in silico.PLoS computational biology · 2026Article
- Bmp9 regulates Notch signaling and the temporal dynamics of angiogenesis via Lunatic Fringe.Developmental cell · 2026Article
- Bayesian Decision-Making Shapes Phenotypic Landscapes from Differentiation to Cancer.Entropy (Basel, Switzerland) · 2026Article
- Predicted Effects of Patient Variability and Notch Signaling on In Situ Vascular Tissue Engineering.Annals of biomedical engineering · 2026Article
- Developmental regulation of intestinalbioRxiv : the preprint server for biology · 2025Article
- Molecular Landscape of Prostate Cancer Across Age Groups: Impact on Prognosis and Treatment Outcomes.International journal of molecular sciences · 2025Review
- Temporal dynamics of angiogenesis: the emerging role of mechanoregulated pathways.Biochemical Society transactions · 2025Review
- A model of Notch signalling control of angiogenesis: Evidence of a role for Notch ligand heterodimerization.PLoS computational biology · 2025Article
- YAP/TAZ drives Notch and angiogenesis mechanoregulation in silico.NPJ systems biology and applications · 2024Article
- Emergent order in epithelial sheets by interplay of cell divisions and cell fate regulation.PLoS computational biology · 2024Article
- Microenvironmental entropy dynamics analysis reveals novel insights into Notch-Delta-Jagged decision-making mechanism.iScience · 2024Article
- A mathematical framework for understanding the spontaneous emergence of complexity applicable to growing multicellular systems.PLoS computational biology · 2024Article
- Spatial-temporal order-disorder transition in angiogenic NOTCH signaling controls cell fate specification.eLife · 2024Article
- Review
- Tumour follower cells: A novel driver of leader cells in collective invasion (Review).International journal of oncology · 2023Review
- Theoretical and computational tools to model multistable gene regulatory networks.Reports on progress in physics. Physical Society (Great Britain) · 2023Review
- Jag1-Notch cis-interaction determines cell fate segregation in pancreatic development.Nature communications · 2023Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling pathway mediates cell-fate determination during embryonic development, wound healing, and tumorigenesis. This pathway is activated when the ligand Delta or the ligand Jagged of one cell interacts with the Notch receptor of its neighboring cell, releasing the Notch Intracellular Domain (NICD) that activates many downstream target genes. NICD affects ligand production asymmetrically--it represses Delta, but activates Jagged. Although the dynamical role of Notch-Jagged signaling remains elusive, it is widely recognized that Notch-Delta signaling behaves as an intercellular toggle switch, giving rise to two distinct fates that neighboring cells adopt--Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Here, we devise a specific theoretical framework that incorporates both Delta and Jagged in Notch signaling circuit to explore the functional role of Jagged in cell-fate determination. We find that the asymmetric effect of NICD renders the circuit to behave as a three-way switch, giving rise to an additional state--a hybrid Sender/Receiver (medium ligand, medium receptor). This phenotype allows neighboring cells to both send and receive signals, thereby attaining similar fates. We also show that due to the asymmetric effect of the glycosyltransferase Fringe, different outcomes are generated depending on which ligand is dominant: Delta-mediated signaling drives neighboring cells to have an opposite fate; Jagged-mediated signaling drives the cell to maintain a similar fate to that of its neighbor. We elucidate the role of Jagged in cell-fate determination and discuss its possible implications in understanding tumor-stroma cross-talk, which frequently entails Notch-Jagged communication.
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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.