Affinage

DLL4

Delta-like protein 4 · UniProt Q9NR61

Length
685 aa
Mass
74.6 kDa
Annotated
2026-06-09
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DLL4 is a transmembrane Notch ligand that operates as the central rheostat of sprouting angiogenesis, signaling in trans through Notch1 to enforce lateral inhibition that fixes the ratio of tip to stalk cells during VEGF-driven vascular outgrowth (PMID:17259973, PMID:17183323). Within this circuit DLL4 expression fluctuates in individual endothelial cells, and the synchronization versus asynchrony of these oscillations toggles vessels between expansion and branching (PMID:27074663); the integrated level of Notch activity, more than direct cell-cell contact, determines outcome and channels tip-derived cells into arteries (PMID:28714968). DLL4 selectively activates NOTCH1 over NOTCH2 through its N-terminal ectodomain and, unlike DLL1, acts as an efficient cis-inhibitor, properties that account for its distinct functional output (PMID:30289388, PMID:26114479). Its signaling strength is set by a competitive balance with Jagged1 that is tuned by Fringe glycosyltransferases (PMID:19524514, PMID:31789590). DLL4 transcription is driven by a convergent set of inputs—VEGF/HIF-1alpha-arterial programs (PMID:17045587), Wnt/beta-catenin (PMID:20627076), integrin-laminin adhesion acting through FOXC2 (PMID:21474814, PMID:29380370), and LDB2/LMO2/TAL1/GATA2 complexes (PMID:28946938)—and is repressed by Slug and by YAP/TAZ (PMID:33106502, PMID:31335323); protein levels are further controlled post-transcriptionally by IRES-mediated translation under hypoxia/ER stress (PMID:30691003), by deubiquitination via USP5 (PMID:30586693), and by junctional stabilization through the PDZ proteins SYNJ2BP and MPDZ that link DLL4 to Nectin-2 at adherens junctions (PMID:24025447, PMID:29620522). Through these mechanisms DLL4-Notch controls arterio-venous and coronary vascular morphogenesis (PMID:34497373, PMID:31789590), lymphatic sprouting and lacteal maintenance via EphrinB2 and VEGFR3 (PMID:21700774, PMID:26529256), endothelial quiescence in cooperation with BMP9/ALK1 and P27KIP1 (PMID:26471266), and vascular barrier function through a Sox17-Dll4-SREBP1 axis that limits transcytosis (PMID:32078435). Beyond the vasculature DLL4 governs T-cell lineage commitment and thymic Treg generation (PMID:20548034, PMID:22547652), hematoendothelial fate decisions (PMID:25778099, PMID:32149421), and an endothelial-to-myofiber Dll4-Notch2 axis controlling skeletal muscle mass (PMID:35228746); it is also exploited in tumor angiogenesis and metastasis and in macrophage-driven atherosclerosis (PMID:17183323, PMID:21803743, PMID:38346959).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Establishing whether DLL4 is required for endothelial differentiation versus proliferation defined its core role as a brake on uncontrolled vascular growth.

    Evidence DLL4-selective neutralizing antibody with in vitro endothelial assays and tumor xenografts

    PMID:17183323

    Open questions at the time
    • Did not resolve which Notch receptor mediates the effect
    • Mechanism of fate specification downstream of Notch not defined
  2. 2007 High

    Resolving how endothelial sprouts select tip versus stalk identity showed DLL4-Notch1 lateral inhibition sets the tip:stalk ratio in response to VEGF.

    Evidence Dll4 haploinsufficiency, endothelial Notch1 deletion, gamma-secretase inhibitors and retinal imaging in mice

    PMID:17259973

    Open questions at the time
    • Did not explain how DLL4 levels are dynamically encoded across the sprout
    • Transcriptional control of DLL4 by VEGF left unaddressed
  3. 2009 High

    Defining why two Notch ligands have opposing angiogenic roles revealed that Fringe glycosylation tilts a DLL4-versus-Jagged1 competitive equilibrium.

    Evidence Genetic Jagged1/Dll4 manipulation and Fringe glycosyltransferase studies in mouse retinal angiogenesis

    PMID:19524514

    Open questions at the time
    • Quantitative thresholds of ligand balance not defined
    • Structural basis of Fringe-dependent discrimination unresolved
  4. 2010 Medium

    Identifying upstream transcriptional drivers connected angiogenic signaling and Wnt to DLL4, and quantified DLL4's distinct potency in lineage commitment.

    Evidence Endothelial beta-catenin stabilization in mice plus DLL4 promoter analysis; OP9 dose-titration cocultures comparing DLL1 and DLL4

    PMID:20548034 PMID:20627076

    Open questions at the time
    • Direct beta-catenin promoter occupancy not fully resolved
    • Molecular basis of DLL4's greater potency versus DLL1 not yet mapped
  5. 2011 Medium

    Mapping additional inducers and downstream effectors extended DLL4 control to integrin-laminin adhesion, lymphatic development, and vessel regression.

    Evidence Integrin siRNA with laminin adhesion and 3D sprouting assays; anti-Dll4/Notch1 antibodies in lymphatic and oxygen-induced retinopathy models

    PMID:21474814 PMID:21498671 PMID:21700774

    Open questions at the time
    • FOXC2 shown necessary but not sufficient for DLL4 induction
    • Link between EphrinB2 regulation and VEGFR3 signaling mechanistically incomplete
  6. 2013 Medium

    Discovering DLL4 PDZ-motif binding partners explained how DLL4 protein is stabilized and positioned at adherens junctions to sustain Notch output.

    Evidence Co-IP, protein stability assays and siRNA in endothelial cells (SYNJ2BP); later MPDZ Co-IP plus in vivo hindbrain and tumor angiogenesis

    PMID:24025447 PMID:29620522

    Open questions at the time
    • Single-lab Co-IP without independent reciprocal validation for each partner
    • How junctional localization tunes trans-signaling strength not quantified
  7. 2015 Medium

    A series of studies expanded DLL4 into adult homeostasis—lacteal maintenance, endothelial quiescence, pericyte regulation, and hematoendothelial fate.

    Evidence Lymphatic-specific Dll4 deletion with fat-absorption assays; BMP9/ALK1 reciprocal inhibition with proteomics; Notch3 pericyte cocultures; hESC clonal differentiation

    PMID:25778099 PMID:25791711 PMID:26471266 PMID:26529256

    Open questions at the time
    • Interdependence of DLL4 and BMP9/ALK1 mechanistically partial
    • Context-specificity of which Notch receptor DLL4 engages not uniformly resolved
  8. 2016 Medium

    Live imaging of DLL4 dynamics reframed angiogenic patterning as an oscillatory system in which synchronization switches branching to expansion.

    Evidence In vivo retinal live imaging and ES-cell sprouting assays with DLL4 overexpression and Notch inhibition

    PMID:27074663

    Open questions at the time
    • Molecular clock generating DLL4 oscillations not identified
    • Single-lab observation
  9. 2017 High

    Testing whether direct DLL4 contact or net Notch level dominates showed integrated Notch activity directs tip-derived cells into arteries.

    Evidence Mosaic Dll4 deletion and tip-cell genetic targeting in postnatal mouse retina

    PMID:28714968

    Open questions at the time
    • How tip cells retain function without Dll4 not fully explained
    • Compensating ligand sources not defined
  10. 2018 High

    Biochemical and genetic dissection of the ectodomain established the molecular basis of DLL4 receptor selectivity and additional transcriptional regulators.

    Evidence Chimeric ligand knock-in mice and binding studies (NOTCH1 vs NOTCH2 selectivity); LDB2 promoter complexes; LPS-FOXC2-ERK promoter axis

    PMID:28946938 PMID:29380370 PMID:30289388

    Open questions at the time
    • Structural detail of the discriminating N-terminal region not solved
    • Combinatorial logic among transcriptional inputs unresolved
  11. 2020 High

    Identifying the Sox17-Dll4-SREBP1 axis revealed a transcytosis-based, junction-independent mechanism by which DLL4 maintains the vascular barrier.

    Evidence Antibody and genetic Dll4/Notch1 inactivation, Sox17 deletion, transcriptomics and SREBP1 inhibition in retinal models

    PMID:32078435

    Open questions at the time
    • Direct molecular link from NICD to SREBP1 activation not fully traced
    • Caveolae-formation step mechanistically incomplete
  12. 2022 High

    Demonstrating an endothelial-to-myofiber Dll4-Notch2 axis and engineering high-affinity DLL4 variants extended DLL4 biology beyond the vasculature and into reagent design.

    Evidence Myofiber Notch2 conditional knockout with atrophy/overload models; affinity-matured DeltaMAX variant with quantitative binding and functional assays

    PMID:35228746 PMID:36050494

    Open questions at the time
    • How released DLL4 acts without cell-cell contact mechanistically open
    • In vivo therapeutic translation of engineered variants not established
  13. 2024 Medium

    Disease-context studies positioned DLL4 in macrophage-driven atherosclerosis and exosome-mediated intercellular Notch signaling.

    Evidence Macrophage-specific DLL4 knockout in atherosclerotic mice; Epsin1-dependent DLL4 exosome sorting with macrophage activation assays

    PMID:37016580 PMID:38346959

    Open questions at the time
    • Mechanism by which DLL4 triggers VSMC senescence partial
    • Single-lab disease-context findings

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis and quantitative thresholds that convert DLL4 oscillation, cis-inhibition, and ligand competition into specific cell-fate outputs across tissues remain unresolved.
  • No unified model linking DLL4 expression dynamics to receptor selection in vivo
  • Mechanism of contact-independent (soluble/exosomal) DLL4 signaling incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
JAG1MPDZNOTCH1NOTCH2NOTCH3NOTCH4SYNJ2BP

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 DLL4-Notch1 signaling between endothelial cells restricts tip-cell formation in response to VEGF, establishing the ratio between tip and stalk cells required for correct sprouting and branching. Genetic inactivation of one Dll4 allele or endothelial-specific Notch1 deletion increases tip cell numbers, while Notch activation reduces them, demonstrating lateral inhibition within angiogenic sprouts. Genetic mouse models (Dll4 haploinsufficiency, endothelial-specific Notch1 deletion), gamma-secretase inhibitors, soluble Jagged1 peptide treatment, retinal vascular imaging Nature High 17259973
2009 Jagged1 antagonizes DLL4-Notch signaling in cells expressing Fringe family glycosyltransferases: upon Notch glycosylation by Fringe, DLL4-Notch signaling is enhanced while Jagged1 has weak signaling capacity and competes with DLL4, establishing that the equilibrium between two Notch ligands with opposing roles regulates angiogenesis. Genetic mouse models of Jagged1 and Dll4 manipulation, Fringe glycosyltransferase functional studies, in vivo retinal angiogenesis assays Cell High 19524514
2006 Neutralizing DLL4 with a selective antibody renders endothelial cells hyperproliferative and causes defective cell fate specification/differentiation both in vitro and in vivo, demonstrating that DLL4-mediated Notch signaling regulates endothelial cell proliferation and differentiation during active vascularization. DLL4-selective neutralizing antibody, in vitro endothelial cell assays, in vivo tumor xenograft models, histological analysis Nature High 17183323
2017 Genetic experiments in postnatal mice reveal that the level of active Notch signaling is more important than direct DLL4-mediated cell-cell communication. Endothelial tip cells retain their function without Dll4 and are not replaced by adjacent Dll4-positive cells. Instead, Dll4-Notch signaling directs tip-derived endothelial cells into developing arteries, coupling sprouting angiogenesis and artery formation. Conditional genetic targeting of endothelial tip cells in vivo, mosaic Dll4 deletion, postnatal retinal angiogenesis analysis Nature cell biology High 28714968
2006 Hypoxia via HIF-1alpha induces DLL4 expression and downstream Notch target genes Hey1 and Hey2. The activated Dll4-Notch-Hey2 signaling cascade leads to repression of COUP-TFII in endothelial progenitor cells, promoting arterial cell fate decision. Hey factors provide negative feedback by repressing HIF-1alpha-induced gene expression. Promoter analysis, HIF-1alpha induction in cell lines, endothelial progenitor cell culture, gene expression analysis Experimental cell research Medium 17045587
2010 Beta-catenin (Wnt signaling) upregulates Dll4 transcription and strongly increases Notch signaling in endothelium, leading to functional and morphological vascular alterations including lack of vascular remodeling and loss of venous identity. Both in vivo and in vitro data establish a mechanistic link between Wnt and Notch signaling via DLL4. Endothelial-specific stabilization of beta-catenin in mice, in vitro endothelial cell assays, DLL4 promoter transcriptional analysis Developmental cell Medium 20627076
2011 DLL4-mediated Notch signaling in tumor endothelium increases large vessel formation, reduces VEGFR2 expression in large blood vessels, decreases VEGFR3 overall, and decreases hypoxia-induced VEGF while increasing VEGFR1 in tumor stroma — multiple mechanisms by which DLL4-Notch confers resistance to bevacizumab (anti-VEGF) therapy. Retroviral DLL4 transduction of glioblastoma cells, tumor xenografts, bevacizumab treatment, gamma-secretase inhibitor treatment, molecular analysis of resistance mechanisms Cancer research Medium 21803743
2009 DLL4 on dendritic cells is induced by pathogen-associated signals through TLR activation (but not by early inflammatory cytokines IL-1 and IL-18), and DLL4 signaling upregulates Rorc expression in T cells and directly targets Rorc and Il17 gene promoters to promote Th17 differentiation. DLL4 also inhibits Th2 cytokine production. In vitro T cell differentiation co-culture assays, siRNA knockdown, Notch signaling inhibition, gene promoter analysis Journal of immunology Medium 19494260
2011 DLL4-Notch1 signaling blockade disrupts postnatal lymphatic development by downregulating EphrinB2 expression (required for VEGFR3/VEGFC signaling), resulting in reduced lymphangiogenic sprouting, dilation of collecting lymphatic vessels with reduced mural cell coverage, and impaired wound healing/lymphangiogenesis. Function-blocking antibodies against Notch1 and Dll4 in mice, lymphatic development analysis, EphrinB2 expression analysis, wound healing model Blood Medium 21700774
2011 DLL4/Notch pathway regulates vessel regression by modulating vasoconstriction and blood flow: Dll4/Notch inhibition upregulates vasodilators (adrenomedullin) and suppresses vasoconstrictors (angiotensinogen), maintaining blood flow and preventing capillary regression. Angiotensin II induces rapid nonperfusion and regression of developing retinal capillaries. Genetic and pharmacologic Dll4/Notch inhibition in retinal oxygen-induced retinopathy model, Notch-regulated ankyrin repeat protein deletion, vasoactive molecule expression analysis Blood Medium 21498671
2015 DLL4 expression in intestinal lacteals requires activation of VEGFR3 and VEGFR2, and genetic inactivation of Dll4 in lymphatic endothelial cells leads to lacteal regression and impaired dietary fat uptake, demonstrating a role for continuous DLL4 signaling in adult lymphatic vessel maintenance and function. Lymphatic endothelial cell-specific genetic inactivation of Dll4, VEGFR2/3 blocking experiments, dietary fat absorption assays, high-resolution intestinal stroma analysis The Journal of clinical investigation High 26529256
2011 Adhesion of endothelial cells to laminin-111 via alpha2beta1 and alpha6beta1 integrins triggers DLL4 expression, leading to subsequent Notch pathway activation. Foxc2 transcription is required but not sufficient for DLL4 induction. VEGF stimulates laminin gamma1 deposition, which leads to integrin signaling and DLL4 induction. Loss of integrins alpha2 or alpha6 mimics DLL4 silencing effects. siRNA knockdown of integrins, endothelial cell adhesion assays on laminin-111, 3D matrigel sprouting assay, VEGF stimulation experiments Circulation research Medium 21474814
2015 Synaptojanin-2 binding protein (SYNJ2BP) physically interacts with the PDZ binding motif of DLL4 (and DLL1 but not Jagged-1), is preferentially expressed in stalk cells, enhances DLL4 protein stability, and promotes Notch signaling in endothelial cells. SYNJ2BP enables DLL4 interaction with Nectin-2 at adherens junctions. Co-immunoprecipitation, protein stability assays, siRNA knockdown, in vivo vascular density analysis in immunocompromised mice, in vitro endothelial cell assays Circulation research Medium 24025447
2014 DLL4-containing exosomes can travel through 3D collagen matrix, transfer DLL4 protein to distant endothelial tip cells, activate Notch signaling in recipient cells, cause tip cell filopodia retraction, suppress sprout formation, increase endothelial cell motility, and suppress endothelial cell proliferation. 3D microfluidic device, time-lapse confocal microscopy, exosome isolation and application, Notch signaling readouts Scientific reports Medium 24504253
2010 At limiting expression levels, DLL4 maintains the ability to inhibit B lineage choice and induce T lineage commitment at lower expression levels than DLL1. DLL4 expressed at physiological levels supports T lineage cells and is permissive for myeloid cells while still inhibiting B lymphopoiesis. These properties correlate with DLL4's more efficient induction of Notch target genes and inhibition of B/myeloid-specific transcription factors. OP9 stromal cell lines expressing incrementally discrete levels of Dll1 or Dll4, hematopoietic progenitor coculture, Notch target gene expression analysis, lineage output analysis Journal of immunology Medium 20548034
2015 DLL4/Notch1 and BMP9/ALK1 signaling pathways are interdependent: canonical BMP9 signaling via ALK1-Smad1/5/9 is disrupted by inhibition of Notch signaling, and DLL4 activity is suppressed when the ALK1-Smad1/5/9 pathway is inhibited. BMP9/DLL4 synergistically induces complete endothelial quiescence requiring P27KIP1 and upregulation of thrombospondin-1. Human endothelial cell stimulation with BMP9 and DLL4, Notch and ALK1 inhibitors, Dll4+/- mouse vascular analysis, proteomics Arteriosclerosis, thrombosis, and vascular biology Medium 26471266
2016 DLL4 expression fluctuates in individual endothelial cells within sprouting vessels. High VEGF or DLL4 overexpression leads to Notch-dependent synchronization of DLL4 fluctuations within clusters, switching vessels from branching to expansion. Normal asynchronous Dll4 oscillations drive heterogeneity and branching, while synchronization drives vessel expansion. Live imaging in mouse retina in vivo, mouse embryonic stem cell-derived sprouting assays, DLL4 overexpression, Notch inhibition eLife Medium 27074663
2015 Leader cell identity during collective cell migration is dynamically regulated by DLL4 signaling through Notch1 and cellular stress. DLL4 is induced in leader cells after creation of a cell-free region, and leader cells are regulated via Notch1-DLL4 lateral inhibition. Mechanical stress inhibits DLL4 expression and leader cell formation. Single-cell gene expression analysis, computational modeling, time-lapse microscopy, Notch1-DLL4 inhibition Nature communications Medium 25766473
2015 CCM1 silencing in endothelial cells causes decreased Notch3 activity in cocultured pericytes. Endothelial DLL4 stimulates Notch3 receptors on human brain pericytes; active Notch3 induces expression of PDGFRB2, N-Cadherin, HBEGF, TGFB1, NG2, and S1P genes, enhances pericyte adhesion to endothelial cells, limits pericyte migration/invasion, and enhances pericyte antiangiogenic function. Genetic manipulation of primary human endothelial cells and brain pericytes, Ccm1/Ccm2 endothelial-specific ablation in mouse models, Notch3 siRNA knockdown, pericyte-endothelial coculture Stroke Medium 25791711
2018 Multiple PDZ domain protein (MPDZ) physically interacts with the intracellular carboxyterminus of DLL4 (and DLL1) and enables their interaction with the adherens junction protein Nectin-2. MPDZ inactivation leads to impaired Notch signaling activity and increased blood vessel sprouting; tumor angiogenesis was enhanced upon endothelial-specific MPDZ inactivation. Co-immunoprecipitation, MPDZ gene inactivation in cellular models, embryonic mouse hindbrain vascular analysis, tumor angiogenesis models eLife Medium 29620522
2019 LPA4/LPA6-mediated Gα12/Gα13-Rho-ROCK signaling activates YAP/TAZ in endothelial cells; YAP/TAZ knockdown increases β-catenin- and NICD-mediated endothelial DLL4 expression. LPA4/LPA6 or YAP/TAZ knockdown blocks EC sprouting, rescued by Notch inhibitor, demonstrating that LPA-YAP/TAZ signaling promotes angiogenesis by repressing DLL4. Endothelial-specific Lpa4;Lpa6 double knockout mice, siRNA knockdown of YAP/TAZ, fibrin gel sprouting assay, retinal angiogenesis analysis, Notch inhibition rescue experiments The Journal of clinical investigation Medium 31335323
2020 Slug (SNAI2) transcription factor suppresses DLL4-Notch signaling in angiogenic endothelial cells, thereby promoting VEGFR2 expression. EC-specific Slug re-expression or reduced Notch signaling (gamma-secretase inhibition or Dll4 loss) rescues retinal angiogenesis in Slug knockout mice. Endothelial Slug is activated by SDF1alpha via CXCR4 and MAP kinase ERK5. Slug knockout mice, EC-specific re-expression, gamma-secretase inhibition, Dll4 loss-of-function, VEGF signaling inhibition, CXCR4/ERK5 pathway analysis Nature communications Medium 33106502
2019 Indoxyl sulfate induces DLL4 protein expression in macrophages via inhibition of the ubiquitin-proteasome pathway through the deubiquitinating enzyme USP5, triggering Notch signaling. Macrophage uptake of indoxyl sulfate is mediated by OATP2B1; DLL4 antibody and OATP2B1 siRNA inhibit proinflammatory macrophage activation and atherosclerotic lesion development in mice. In vitro macrophage treatment with indoxyl sulfate, global proteomics, siRNA knockdown (macrophage-targeted lipid nanoparticles), 5/6 nephrectomy mouse model, Dll4 antibody treatment, Ldlr-/- atherosclerosis model Circulation Medium 30586693
2019 In the context of diabetic wounds, high glucose levels activate a positive Dll4-Notch1 feedback loop, and Notch1 inactivation specifically in keratinocytes cancels the repressive effects of this loop on wound healing in diabetes, demonstrating that the Dll4-Notch1 loop in keratinocytes impairs diabetic wound healing. Genetic loss-of-function in diabetic mouse models, keratinocyte-specific Notch1 inactivation, local Notch signaling inhibition, wound healing analysis Proceedings of the National Academy of Sciences of the United States of America Medium 30886104
2020 Both antibody-based and genetic inactivation of Dll4 or Notch1 induces hyperpermeability in arterial endothelial cells by increasing transcytosis without junctional destabilization. Endothelial Sox17 deletion represses Dll4 in retinal arteries, phenocopying Dll4 blockade. Dll4 blocking activates SREBP1-mediated lipogenic transcription and caveolae formation. Inhibition of SREBP1 or VEGF-VEGFR2 attenuates Dll4 blockade-driven retinal leakage, establishing a Sox17-Dll4-SREBP1 axis controlling transcytosis independently of tight junctions. Antibody-based and genetic Dll4/Notch1 inactivation, Sox17 endothelial deletion, transcriptomic profiling, SREBP1 inhibition, VEGFR2 inhibition, hypertension-induced retinal edema model Circulation research High 32078435
2022 In atrophic conditions, microvascular endothelium upregulates and releases the Notch ligand DLL4, which activates muscular Notch2 without direct cell-cell contact. Inhibition of the Dll4-Notch2 axis substantially prevents disuse- or diabetes-induced muscle atrophy and promotes overloading-induced muscle hypertrophy in mice, establishing an endothelial-to-muscle signaling axis controlling skeletal muscle mass. Myofiber Notch2 conditional knockout, Dll4 inhibition, disuse and diabetic atrophy mouse models, mechanical overload model, DLL4/Notch2 axis analysis Nature metabolism High 35228746
2015 DLL4 is expressed in a sub-population of bipotent hematoendothelial progenitors (HEPs) in hESCs and segregates their hematopoietic versus endothelial potential. DLL4-high HEPs are enriched for endothelial potential, while DLL4-low/-negative HEPs are committed to hematopoietic lineage. DLL4 stimulation enhances hematopoietic differentiation of HEPs and increases clonogenic hematopoietic progenitors. hESC differentiation, clonal analysis, transcriptome analysis, confocal microscopy of embryoid bodies, DLL4 stimulation of HEPs Leukemia Medium 25778099
2020 Dll4 acts as a negative regulator of intra-aortic hematopoietic cluster (IAHC) recruitment: blocking Dll4 promotes entrance of new hemogenic Gfi1+ cells into IAHC and increases the number of cells acquiring HSC activity. IACHs form through a two-step process where Dll4 inhibits the recruitment phase. Live imaging of organotypic slice cultures, clonal analysis, mathematical modeling, Dll4 blocking experiments in mouse embryos The EMBO journal Medium 32149421
2018 DLL4 preferentially activates NOTCH1 over NOTCH2, whereas DLL1 is equally effective in activating NOTCH1 and NOTCH2. The discriminating potential lies in the region between the N-terminus and EGF repeat three of the ligand ectodomain. The ectodomains dictate selective ligand function in vivo during somitogenesis. Cellular co-culture signaling assays, biochemical binding studies, chimeric ligand knock-in mouse models, somitogenesis and myogenesis analysis eLife High 30289388
2015 DLL4, but not DLL1, is an efficient cis-inhibitor of Notch signaling, causing reduced net activation of Notch in cells co-expressing ligand and receptor. This differential cis-inhibitory property contributes to context-dependent functional divergence between DLL1 and DLL4. Conditional overexpression from same genomic locus (Hprt), Dll1Dll4 knock-in mice, in vitro Notch signaling assays for cis-inhibition and trans-activation PLoS genetics Medium 26114479
2018 LPS/TLR4 signaling induces ERK phosphorylation, which causes FOXC2-ERK protein ligation and ERK-dependent FOXC2 serine/threonine phosphorylation, subsequently activating DLL4 gene expression. FOXC2 binds to the DLL4 promoter in vivo. ERK inhibition or FOXC2 siRNA attenuates LPS-induced DLL4 expression and angiogenic sprouting. TLR4/LPS stimulation in human lung endothelial cells, ERK inhibition, ERK-2 dominant negative transfection, FOXC2-siRNA, in vivo mouse lung analysis, FOXC2+/- mice The Journal of physiology Medium 29380370
2019 The DLL4 5'-UTR harbors an Internal Ribosomal Entry Site (IRES) that is efficiently utilized during hypoxia and ER stress (cap-independent translation). PERK kinase (activated by ER stress) drives DLL4 IRES-mediated translation, and hnRNP-A1 acts as an IRES-Trans-Acting Factor (ITAF) participating in IRES-dependent DLL4 translation during ER stress. IRES reporter assays, PERK inhibition/activation, hnRNP-A1 characterization, hypoxia and ER stress treatment of cells Cancers Medium 30691003
2012 KSHV vGPCR upregulates DLL4 through an ERK-dependent mechanism in lymphatic endothelial cells, while vFLIP induces JAG1 through NFkappaB-dependent signaling. Both ligands signal through NOTCH4 and suppress cell cycle genes in adjacent lymphatic endothelial cells to induce quiescence. KSHV gene expression in lymphatic endothelial cells, ERK and NFkappaB pathway inhibition, gene expression profiling, functional Notch signaling assays PLoS pathogens Medium 19816565
2019 TMZ treatment promotes nuclear translocation of MMP14 followed by extracellular release of DLL4. Released DLL4 stimulates cleavage of Notch3, its nuclear translocation, and induction of sphering capacity and stemness in glioblastoma cells. Multiple PDX GBM models and glioma cell lines, MMP14 expression/localization analysis, Kiloplex ELISA-based protein array, DLL4/Notch3 functional studies International journal of cancer Medium 31443114
2019 Soluble DLL4 activates Notch signaling in endothelial cells, increases VE-cadherin expression at intercellular junctions (but not ZO-1), and decreases vascular permeability. This permeability reduction acts through a cAMP/PKA pathway: PKA inhibition reverses the DLL4-mediated permeability reduction and reduces Hey1 expression. PKA knockdown reduces VE-cadherin junctional expression. Recombinant soluble DLL4 treatment of EC monolayers, gamma-secretase inhibitor, PKA inhibitors, hydraulic conductivity in rat mesenteric microvessels in vivo, FITC-albumin permeability assays American journal of physiology. Heart and circulatory physiology Medium 30681366
2021 In zebrafish valvulogenesis, blood flow activates Notch signaling, which drives lateral inhibition between endocardial cells mediated by DLL4. DLL4-positive endocardial cells ingress into the cardiac jelly to form an abluminal cell population in response to Wnt9a (produced via Erk5-Klf2-Wnt9a cascade). Mechanical stimulation activates parallel mechanosensitive signaling pathways (Notch and Klf2) that intersect to drive valve formation. Zebrafish genetic models, live imaging, DLL4-positive cell lineage tracking, Notch and Wnt9a pathway perturbation experiments Cell reports Medium 34610316
2021 Pre-existing embryonic coronary plexus expresses DLL4, and DLL4-NOTCH1 signaling mediates angiogenic expansion of this plexus to vascularize the expanding myocardium in neonates, and also revascularizes the regenerating neonatal heart. Ventricular endocardial cells do not contribute to new coronary vessels. Lineage-tracing, gain- and loss-of-function genetic experiments in mice, neonatal heart regeneration model Nature cell biology High 34497373
2019 Coronary arterial development requires a DLL4-Jag1-EphrinB2 signaling cascade: endocardial Jag1 removal blocks sinus venosus capillary sprouting, while Dll4 inactivation stimulates excessive capillary growth. Forced Dll4 expression or Mfng (glycosyltransferase) blocks coronary plexus remodeling and arterial differentiation. EphrinB2 is a critical effector of antagonistic Dll4 and Jag1 functions in arterial morphogenesis. Endocardial Jag1 conditional deletion, Dll4 inactivation, forced Dll4/Mfng expression, Efnb2 endocardial deletion, angiogenic rescue experiments in ventricular explants and human endothelial cells eLife High 31789590
2018 LDB2 (LIM-domain binding protein 2) regulates basal and VEGF-induced DLL4 expression in endothelial cells by binding to the DLL4 promoter region through oligomeric complexes with LMO2/TAL1/GATA2. LDB2 overexpression increases DLL4 expression; LDB2 knockdown decreases DLL4 expression and enhances endothelial sprouting. siRNA knockdown and overexpression of LDB2, DLL4 promoter binding assays, zebrafish ldb2-morpholino, in vitro sprouting/tubular network assays BMB reports Medium 28946938
2022 Affinity-matured DLL4 variant (DeltaMAX) binds human and murine Notch receptors with 500- to 1000-fold increased affinity compared to wild-type human DLL4. DeltaMAX potently activates Notch in plate-bound, bead-bound, and cellular formats. As a soluble decoy, DeltaMAX inhibits Notch in reporter and neuronal differentiation assays, demonstrating dual agonist/antagonist utility. Protein engineering/affinity maturation, in vitro Notch activation assays (plate-bound, bead-bound, cellular), reporter assays, neuronal differentiation assays, T cell stimulation assays Nature chemical biology High 36050494
2023 Epsin1 modulates the sorting of DLL4 into exosomes from tubular epithelial cells under high glucose conditions. Exosomes enriched with DLL4 are captured by macrophages and promote M1 macrophage activation via Notch1 (N1ICD) activation. Epsin1 knockdown reduces DLL4 in TEC-exosomes and inhibits macrophage N1ICD activation and iNOS expression. Mass spectrometry of urine exosomes, Epsin1 siRNA knockdown, in vitro THP-1 macrophage treatment with exosomes, in vivo C57BL/6 mouse model, western blot, db/db diabetic mice Molecular therapy Medium 37016580
2012 MEDI0639 (anti-DLL4 antibody) inhibits the binding of Notch1 to DLL4 via a novel epitope not previously described, reversing Notch1-mediated suppression of HUVEC growth in vitro. MEDI0639 promotes tubule formation in 3D endothelial outgrowth assay (disrupting Dll4-Notch axis), but inhibits tubule formation in 2D endothelial-fibroblast coculture. In vivo, MEDI0639 promotes human vessel formation and reduces mural cell coverage. Notch1-DLL4 binding inhibition assays, HUVEC growth assays, 3D and 2D angiogenesis assays, in vivo human endothelial cell angiogenesis assay in mice Molecular cancer therapeutics Medium 22679110
2024 Palmitic acid induces macrophage DLL4 signaling, which in turn triggers senescence in vascular smooth muscle cells, reducing collagen synthesis and deposition, thus promoting atherosclerotic plaque instability. Macrophage-specific DLL4 knockout in atherosclerotic mice leads to reduced plaque burden and improved stability. Human cohort studies, macrophage-specific DLL4 knockout in atherosclerotic mouse models, palmitic acid treatment of macrophages, vascular smooth muscle cell senescence assays Nature communications Medium 38346959
2012 Dll4-Notch signaling in DLL4-expressing cancer cells (SCLC) plays a critical role in liver metastasis by regulating NF-κB signaling. Dll4-Fc (soluble DLL4) acts as a blocker, and Dll4-Fc-expressing cancer cells show downregulated NF-κB activities (both classical and alternative pathways) by reducing Notch1 signaling, resulting in reduced liver metastasis. Soluble Dll4-Fc generation, SCLC cell line transduction, mouse liver metastasis model, PCR array analysis, electrophoretic mobility shift assay for NF-κB activity, Notch1 signaling analysis Molecular cancer therapeutics Medium 22989420
2012 Dll4 blockade (pharmacological or genetic) induces accumulation of thymic dendritic cells and CD4+CD25+FoxP3+ regulatory T cells in the thymic cortex. Dll4 blockade converts DN1 T cell progenitors to immature DCs that induce Treg differentiation through a Flt3-independent, DC-dependent mechanism requiring MHC II expression. This mechanism depends on transcriptional upregulation of PU.1, Irf-4, Irf-8, and CSF-1. Pharmacological Dll4 blockade, genetic inactivation models, thymectomy experiments, DC-T cell coculture, anti-Dll4 antibody treatment in type 1 diabetes model The Journal of experimental medicine Medium 22547652
2019 VEGF165 inhibits pro-fibrotic differentiation of endometrial stromal cells via the DLL4/Notch4/Smad7 pathway; inhibiting Smad7 or Notch4 blocks the anti-fibrotic effect of VEGF165, demonstrating that DLL4 and Notch4 are essential downstream molecules for VEGF165's anti-fibrotic function. VEGF165 treatment of human primary endometrial stromal cells, conditional VEGF reduction in mice, Smad7 and Notch4 inhibition, TGFbeta1-induced fibrosis model Cell death & disease Medium 31515487

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 1375 17259973
2009 The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell 900 19524514
2006 Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 792 17183323
2011 Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells. Gastroenterology 352 21238454
2017 Dll4 and Notch signalling couples sprouting angiogenesis and artery formation. Nature cell biology 331 28714968
2009 DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell stem cell 322 19664991
2010 The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Developmental cell 265 20627076
2011 DLL4-Notch signaling mediates tumor resistance to anti-VEGF therapy in vivo. Cancer research 191 21803743
2006 Hypoxia-mediated activation of Dll4-Notch-Hey2 signaling in endothelial progenitor cells and adoption of arterial cell fate. Experimental cell research 179 17045587
2019 Uremic Toxin Indoxyl Sulfate Promotes Proinflammatory Macrophage Activation Via the Interplay of OATP2B1 and Dll4-Notch Signaling. Circulation 176 30586693
2009 Regulation of T cell activation by Notch ligand, DLL4, promotes IL-17 production and Rorc activation. Journal of immunology (Baltimore, Md. : 1950) 154 19494260
2015 DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport. The Journal of clinical investigation 145 26529256
2010 Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes. Journal of immunology (Baltimore, Md. : 1950) 132 20548034
2015 Endothelial Jagged1 antagonizes Dll4 regulation of endothelial branching and promotes vascular maturation downstream of Dll4/Notch1. Arteriosclerosis, thrombosis, and vascular biology 107 25767274
2015 Notch1-Dll4 signalling and mechanical force regulate leader cell formation during collective cell migration. Nature communications 104 25766473
2011 The Dll4/Notch pathway controls postangiogenic blood vessel remodeling and regression by modulating vasoconstriction and blood flow. Blood 99 21498671
2019 Lysophosphatidic acid-induced YAP/TAZ activation promotes developmental angiogenesis by repressing Notch ligand Dll4. The Journal of clinical investigation 97 31335323
2010 Anti-DLL4 inhibits growth and reduces tumor-initiating cell frequency in colorectal tumors with oncogenic KRAS mutations. Cancer research 96 21193546
2011 Laminin-binding integrins induce Dll4 expression and Notch signaling in endothelial cells. Circulation research 95 21474814
2009 Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer. British journal of cancer 95 19844231
2016 Synchronization of endothelial Dll4-Notch dynamics switch blood vessels from branching to expansion. eLife 93 27074663
2020 Slug regulates the Dll4-Notch-VEGFR2 axis to control endothelial cell activation and angiogenesis. Nature communications 87 33106502
2005 Expression of Dll4 during mouse embryogenesis suggests multiple developmental roles. Gene expression patterns : GEP 85 15923152
2014 Dll4-containing exosomes induce capillary sprout retraction in a 3D microenvironment. Scientific reports 84 24504253
2011 The Notch1-Dll4 signaling pathway regulates mouse postnatal lymphatic development. Blood 80 21700774
2019 Triggering of a Dll4-Notch1 loop impairs wound healing in diabetes. Proceedings of the National Academy of Sciences of the United States of America 76 30886104
2015 Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome. American journal of human genetics 76 26299364
2010 Combination of Dll4/Notch and Ephrin-B2/EphB4 targeted therapy is highly effective in disrupting tumor angiogenesis. BMC cancer 75 21092311
2013 Dll4-Notch signaling in regulation of tumor angiogenesis. Journal of cancer research and clinical oncology 71 24114288
2015 Cerebral Cavernous Malformation-1 Protein Controls DLL4-Notch3 Signaling Between the Endothelium and Pericytes. Stroke 65 25791711
2007 Anti-Dll4 therapy: can we block tumour growth by increasing angiogenesis? Trends in molecular medicine 61 17822956
2006 Expression of Dll4 and CCL25 in Foxn1-negative epithelial cells in the post-natal thymus. International immunology 59 17158094
2015 DLL4/Notch1 and BMP9 Interdependent Signaling Induces Human Endothelial Cell Quiescence via P27KIP1 and Thrombospondin-1. Arteriosclerosis, thrombosis, and vascular biology 55 26471266
2019 Delta-like ligand 4/DLL4 regulates the capillarization of liver sinusoidal endothelial cell and liver fibrogenesis. Biochimica et biophysica acta. Molecular cell research 54 31233801
2012 Anti-DLL4 has broad spectrum activity in pancreatic cancer dependent on targeting DLL4-Notch signaling in both tumor and vasculature cells. Clinical cancer research : an official journal of the American Association for Cancer Research 54 22952347
2020 Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis. Cell death and differentiation 53 32042099
2012 Cross-talk between leukemic and endothelial cells promotes angiogenesis by VEGF activation of the Notch/Dll4 pathway. Carcinogenesis 52 23239744
2013 Implications of Dll4-Notch signaling activation in primary glioblastoma multiforme. Neuro-oncology 51 23787764
2009 KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia. PLoS pathogens 51 19816565
2019 FKBPL and its peptide derivatives inhibit endocrine therapy resistant cancer stem cells and breast cancer metastasis by downregulating DLL4 and Notch4. BMC cancer 50 30975104
2018 The Role of Dll4/Notch Signaling in Normal and Pathological Ocular Angiogenesis: Dll4 Controls Blood Vessel Sprouting and Vessel Remodeling in Normal and Pathological Conditions. Journal of ophthalmology 50 30116629
2012 MEDI0639: a novel therapeutic antibody targeting Dll4 modulates endothelial cell function and angiogenesis in vivo. Molecular cancer therapeutics 48 22679110
2020 Dll4 Suppresses Transcytosis for Arterial Blood-Retinal Barrier Homeostasis. Circulation research 47 32078435
2015 The Notch ligand DLL4 specifically marks human hematoendothelial progenitors and regulates their hematopoietic fate. Leukemia 47 25778099
2012 Dll4-Fc, an inhibitor of Dll4-notch signaling, suppresses liver metastasis of small cell lung cancer cells through the downregulation of the NF-κB activity. Molecular cancer therapeutics 47 22989420
2020 Notch ligand Dll4 impairs cell recruitment to aortic clusters and limits blood stem cell generation. The EMBO journal 45 32149421
2008 Dll4 activation of Notch signaling reduces tumor vascularity and inhibits tumor growth. Blood 45 18577711
2016 Dll4 Inhibition plus Aflibercept Markedly Reduces Ovarian Tumor Growth. Molecular cancer therapeutics 42 27009216
2012 Dll4-Notch signaling in Flt3-independent dendritic cell development and autoimmunity in mice. The Journal of experimental medicine 42 22547652
2023 Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy. Molecular therapy : the journal of the American Society of Gene Therapy 40 37016580
2022 The endothelial Dll4-muscular Notch2 axis regulates skeletal muscle mass. Nature metabolism 40 35228746
2013 Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and DLL4 and inhibits sprouting angiogenesis. Circulation research 39 24025447
2013 Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of missed abortion. PloS one 38 23950980
2015 MMGZ01, an anti-DLL4 monoclonal antibody, promotes nonfunctional vessels and inhibits breast tumor growth. Cancer letters 37 26739060
2024 Palmitic acid in type 2 diabetes mellitus promotes atherosclerotic plaque vulnerability via macrophage Dll4 signaling. Nature communications 36 38346959
2022 DLL4 and VCAM1 enhance the emergence of T cell-competent hematopoietic progenitors from human pluripotent stem cells. Science advances 36 36001668
2021 Mechanosensitive Notch-Dll4 and Klf2-Wnt9 signaling pathways intersect in guiding valvulogenesis in zebrafish. Cell reports 35 34610316
2015 Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4 In Vivo. PLoS genetics 35 26114479
2014 The expression of VEGF and Dll4/Notch pathway molecules in ovarian cancer. Clinica chimica acta; international journal of clinical chemistry 35 24949865
2014 DLL4 regulates NOTCH signaling and growth of T acute lymphoblastic leukemia cells in NOD/SCID mice. Carcinogenesis 35 25355291
2018 MPDZ promotes DLL4-induced Notch signaling during angiogenesis. eLife 34 29620522
2021 Perinatal angiogenesis from pre-existing coronary vessels via DLL4-NOTCH1 signalling. Nature cell biology 31 34497373
2018 The ectodomains determine ligand function in vivo and selectivity of DLL1 and DLL4 toward NOTCH1 and NOTCH2 in vitro. eLife 31 30289388
2014 Endothelial Delta-like 4 (DLL4) promotes renal cell carcinoma hematogenous metastasis. Oncotarget 31 24931473
2019 Specific NOTCH1 antibody targets DLL4-induced proliferation, migration, and angiogenesis in NOTCH1-mutated CLL cells. Oncogene 30 31616059
2018 Endothelial immune activation programmes cell-fate decisions and angiogenesis by inducing angiogenesis regulator DLL4 through TLR4-ERK-FOXC2 signalling. The Journal of physiology 30 29380370
2016 Arterialization and anomalous vein wall remodeling in varicose veins is associated with upregulated FoxC2-Dll4 pathway. Laboratory investigation; a journal of technical methods and pathology 30 26808710
2019 Activation of Notch signaling by soluble Dll4 decreases vascular permeability via a cAMP/PKA-dependent pathway. American journal of physiology. Heart and circulatory physiology 29 30681366
2019 Coronary arterial development is regulated by a Dll4-Jag1-EphrinB2 signaling cascade. eLife 29 31789590
2014 Distinct expression patterns of Notch ligands, Dll1 and Dll4, in normal and inflamed mice intestine. PeerJ 29 24860699
2021 Substrate stiffness modulates endothelial cell function via the YAP-Dll4-Notch1 pathway. Experimental cell research 27 34543658
2020 DLL1- and DLL4-Mediated Notch Signaling Is Essential for Adult Pancreatic Islet Homeostasis. Diabetes 26 32029480
2020 Highly Expressed DLL4 and JAG1: Their Role in Incidence of Breast Cancer Metastasis. Archives of medical research 26 32111499
2016 A humanized anti-DLL4 antibody promotes dysfunctional angiogenesis and inhibits breast tumor growth. Scientific reports 26 27301650
2015 HDAC5 promotes colorectal cancer cell proliferation by up-regulating DLL4 expression. International journal of clinical and experimental medicine 25 26131280
2013 Clinical implications of DLL4 expression in gastric cancer. Journal of experimental & clinical cancer research : CR 25 23898884
2024 LRP1 induces anti-PD-1 resistance by modulating the DLL4-NOTCH2-CCL2 axis and redirecting M2-like macrophage polarisation in bladder cancer. Cancer letters 24 38462037
2016 DLL4+ dendritic cells: Key regulators of Notch Signaling in effector T cell responses. Pharmacological research 24 27639599
2015 Dengue virus up-regulates expression of notch ligands Dll1 and Dll4 through interferon-β signalling pathway. Immunology 24 25041739
2023 Lactate receptor GPR81 drives breast cancer growth and invasiveness through regulation of ECM properties and Notch ligand DLL4. BMC cancer 23 37993804
2018 Propranolol inhibits proliferation and invasion of hemangioma-derived endothelial cells by suppressing the DLL4/Notch1/Akt pathway. Chemico-biological interactions 23 30130526
2019 TMZ regulates GBM stemness via MMP14-DLL4-Notch3 pathway. International journal of cancer 22 31443114
2017 Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway. Scientific reports 22 28262821
2015 Balancing Efficacy and Safety of an Anti-DLL4 Antibody through Pharmacokinetic Modulation. Clinical cancer research : an official journal of the American Association for Cancer Research 22 26589434
2020 TRIM28 regulates sprouting angiogenesis through VEGFR-DLL4-Notch signaling circuit. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 32918765
2019 Vascular endothelial growth factor 165 inhibits pro-fibrotic differentiation of stromal cells via the DLL4/Notch4/smad7 pathway. Cell death & disease 21 31515487
2017 Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo. BMC cancer 21 28288569
2011 Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat. Biology of reproduction 21 21209419
2020 Amarogentin Inhibits Liver Cancer Cell Angiogenesis after Insufficient Radiofrequency Ablation via Affecting Stemness and the p53-Dependent VEGFA/Dll4/Notch1 Pathway. BioMed research international 20 33145353
2019 The PERK Branch of the Unfolded Protein Response Promotes DLL4 Expression by Activating an Alternative Translation Mechanism. Cancers 20 30691003
2022 Engineered patterns of Notch ligands Jag1 and Dll4 elicit differential spatial control of endothelial sprouting. iScience 19 35602952
2020 DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment. Advanced pharmaceutical bulletin 19 34888208
2019 The bispecific antibody HB-32, blockade of both VEGF and DLL4 shows potent anti-angiogenic activity in vitro and anti-tumor activity in breast cancer xenograft models. Experimental cell research 19 31034805
2012 Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues. Biochemical and biophysical research communications 19 22252294
2022 Dysregulation of the miR-30c/DLL4 axis by circHIPK3 is essential for KSHV lytic replication. EMBO reports 18 35239998
2021 EMS1/DLL4-Notch Signaling Axis Augments Cell Cycle-Mediated Tumorigenesis and Progress in Human Adrenocortical Carcinoma. Frontiers in oncology 18 34858850
2018 LDB2 regulates the expression of DLL4 through the formation of oligomeric complexes in endothelial cells. BMB reports 18 28946938
2022 Affinity-matured DLL4 ligands as broad-spectrum modulators of Notch signaling. Nature chemical biology 17 36050494
2021 Neuritin promotes angiogenesis through inhibition of DLL4/Notch signaling pathway. Acta biochimica et biophysica Sinica 17 33787845
2020 Endothelial Jagged1 Antagonizes Dll4/Notch Signaling in Decidual Angiogenesis during Early Mouse Pregnancy. International journal of molecular sciences 17 32899448

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