Dll1 (Delta-like 1) is a type I transmembrane DSL-family ligand of Notch receptors, with an N-terminal MNNL domain, a DSL domain and eight EGF-like repeats in its ectodomain and a cytoplasmic tail ending in a PDZ-binding motif. Presented at the plasma membrane of signal-sending cells, Dll1 binds Notch1 and Notch2 in trans on neighbouring cells; its ubiquitination by the E3 ligases Mind bomb 1 and Neuralized drives ligand endocytosis and recycling and generates the pulling force that exposes Notch to S2 cleavage, thereby activating canonical Notch-RBP-J signalling. Fringe glycosylation of Notch enhances Dll1 binding. Dll1 itself undergoes ADAM10 shedding and gamma-secretase cleavage, and is recruited to adherens junctions by the PDZ scaffold MAGI1. As the principal activating Delta ligand in many mouse tissues, Dll1 mediates lateral inhibition in neurogenesis, inner-ear hair cell patterning and intestinal secretory lineage selection, and is required for somitogenesis and somite polarity, left-right asymmetry, arterial endothelial identity, marginal zone B cell development and adult neural and muscle stem cell maintenance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001701 in utero embryonic development | NAS PMID:10473134 Expression of the mouse Delta1 gene during organogenesis and... | KEEP AS NON CORE | Summary: NAS from expression studies of Dll1 during organogenesis and in the inner ear. Reason: Broadly consistent with functional data (Dll1 null embryos die mid-gestation; conditional loss affects neurogenesis and hair cell patterning), but these are pleiotropic consequences of Notch activation rather than distinct Dll1 functions. |
| GO:0001756 somitogenesis | IGI PMID:15902259 The Mesp2 transcription factor establishes segmental borders... | KEEP AS NON CORE | Summary: Dll1 is required for somite formation, segmentation clock synchrony and somite polarity. Reason: Well-supported in vivo requirement as the PSM Notch ligand, but a tissue-specific outcome of its ligand function. Supporting Evidence: PMID:12001066 distinct segmentation defects are displayed in embryos mutant for the Notch pathway genes Notch1, Lunatic fringe (Lfng), Delta-like 1 (Dll1), and Delta-like 3 (Dll3). |
| GO:0001756 somitogenesis | IMP PMID:23072809 Lfng regulates the synchronized oscillation of the mouse seg... | KEEP AS NON CORE | Summary: Dll1 is required for somite formation, segmentation clock synchrony and somite polarity. Reason: Well-supported in vivo requirement as the PSM Notch ligand, but a tissue-specific outcome of its ligand function. Supporting Evidence: PMID:12001066 distinct segmentation defects are displayed in embryos mutant for the Notch pathway genes Notch1, Lunatic fringe (Lfng), Delta-like 1 (Dll1), and Delta-like 3 (Dll3). |
| GO:0001757 somite specification | IMP PMID:14960495 Specification of vertebral identity is coupled to Notch sign... | KEEP AS NON CORE | Summary: Dll1 is required for somite formation, segmentation clock synchrony and somite polarity. Reason: Well-supported in vivo requirement as the PSM Notch ligand, but a tissue-specific outcome of its ligand function. Supporting Evidence: PMID:12001066 distinct segmentation defects are displayed in embryos mutant for the Notch pathway genes Notch1, Lunatic fringe (Lfng), Delta-like 1 (Dll1), and Delta-like 3 (Dll3). |
| GO:0001944 vasculature development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0001947 heart looping | IMP PMID:12730124 Notch signaling regulates left-right asymmetry determination... | KEEP AS NON CORE | Summary: Dll1 mutants have left-right asymmetry defects owing to loss of Notch-induced Nodal at the node. Reason: Specific developmental outcome of Dll1-Notch signalling. Supporting Evidence: PMID:12730124 Embryos mutant for the Notch ligand Dll1 or doubly mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry. |
| GO:0002064 epithelial cell development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0002315 marginal zone B cell differentiation | IMP PMID:15146182 Delta-like 1 is necessary for the generation of marginal zon... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0002315 marginal zone B cell differentiation | IMP PMID:19217325 Lunatic and manic fringe cooperatively enhance marginal zone... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0003002 regionalization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0003158 endothelium development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0003323 type B pancreatic cell development | IMP PMID:22529374 Mind bomb 1 is required for pancreatic Ξ²-cell formation. | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0005112 Notch binding | IBA GO_REF:0000033 | ACCEPT | Summary: Dll1 binds Notch1 and Notch2 receptors (trans binding on adjacent cells). Reason: Notch binding is the defining molecular activity of a DSL ligand; core. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells PMID:15574878 increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells |
| GO:0005112 Notch binding | IEA GO_REF:0000120 | ACCEPT | Summary: Dll1 binds Notch1 and Notch2 receptors (trans binding on adjacent cells). Reason: Notch binding is the defining molecular activity of a DSL ligand; core. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells PMID:15574878 increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells |
| GO:0005112 Notch binding | IPI PMID:10958687 Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly in... | ACCEPT | Summary: Dll1 binds Notch1 and Notch2 receptors (trans binding on adjacent cells). Reason: Notch binding is the defining molecular activity of a DSL ligand; core. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells PMID:15574878 increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells |
| GO:0005112 Notch binding | IPI PMID:10958687 Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly in... | ACCEPT | Summary: Dll1 binds Notch1 and Notch2 receptors (trans binding on adjacent cells). Reason: Notch binding is the defining molecular activity of a DSL ligand; core. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells PMID:15574878 increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells |
| GO:0005112 Notch binding | IPI PMID:18676613 The intracellular region of Notch ligands Dll1 and Dll3 regu... | ACCEPT | Summary: Dll1 binds Notch1 and Notch2 receptors (trans binding on adjacent cells). Reason: Notch binding is the defining molecular activity of a DSL ligand; core. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells PMID:15574878 increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells |
| GO:0005112 Notch binding | IPI PMID:21985982 Delta-like 1-Lysine613 regulates notch signaling. | ACCEPT | Summary: Dll1 binds Notch1 and Notch2 receptors (trans binding on adjacent cells). Reason: Notch binding is the defining molecular activity of a DSL ligand; core. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells PMID:15574878 increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells |
| GO:0005112 Notch binding | ISO GO_REF:0000096 | ACCEPT | Summary: Dll1 binds Notch1 and Notch2 receptors (trans binding on adjacent cells). Reason: Notch binding is the defining molecular activity of a DSL ligand; core. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells PMID:15574878 increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells |
| GO:0005112 Notch binding | ISO GO_REF:0000119 | ACCEPT | Summary: Dll1 binds Notch1 and Notch2 receptors (trans binding on adjacent cells). Reason: Notch binding is the defining molecular activity of a DSL ligand; core. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells PMID:15574878 increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Calcium ion binding from InterPro EGF-like Ca-binding domain. Reason: Structural property of EGF repeats, not a characterised Dll1 function. |
| GO:0005515 protein binding | IPI PMID:10958687 Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly in... | MODIFY | Summary: IPI with Notch2 (O35516) / Notch1 (Q01705). Reason: Generic protein binding; the informative MF is Notch binding (also annotated). Proposed replacements: Notch binding Supporting Evidence: PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells |
| GO:0005515 protein binding | IPI PMID:12794186 The Notch ligand Delta1 is sequentially cleaved by an ADAM p... | REMOVE | Summary: IPI with Psen1 (P49769; Dll1 is a gamma-secretase substrate), MT1-MMP/Mmp14 (P50281; Dll1 is cleaved by it), MAGP-2/Mfap5 (Q9QZJ6) and ZO-1/Tjp1 (P39447). Reason: Generic protein binding is uninformative. For Psen1 and MT1-MMP Dll1 is the protease substrate; the other interactions do not define a specific Dll1 molecular function. Removal does not dispute the reported interactions. Supporting Evidence: PMID:12794186 We then show that Dll1 is part of a high-molecular-weight complex containing presenilin1 and undergoes further cleavage by a gamma-secretase-like activity |
| GO:0005515 protein binding | IPI PMID:14529612 Interaction of the MAGUK family member Acvrinp1 and the cyto... | MODIFY | Summary: IPI with the PDZ-domain MAGUK protein Magi2/Acvrinp1 (Q9WVQ1), via the Dll1 C-terminal PDZ-binding motif. Reason: Generic protein binding; the interaction is PDZ-mediated. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:14529612 We delimited the fourth PDZ domain of Acvrinp1 and the PDZ-binding domain of Dll1 as major interacting domains. |
| GO:0005515 protein binding | IPI PMID:15574878 Fringe glycosyltransferases differentially modulate Notch1 p... | MODIFY | Summary: IPI with Notch2 (O35516) / Notch1 (Q01705). Reason: Generic protein binding; the informative MF is Notch binding (also annotated). Proposed replacements: Notch binding Supporting Evidence: PMID:10958687 All of the three DSL proteins bound to endogenous Notch2 on the surface of BaF3 cells |
| GO:0005515 protein binding | IPI PMID:15788413 The extracellular matrix protein MAGP-2 interacts with Jagge... | REMOVE | Summary: IPI with Psen1 (P49769; Dll1 is a gamma-secretase substrate), MT1-MMP/Mmp14 (P50281; Dll1 is cleaved by it), MAGP-2/Mfap5 (Q9QZJ6) and ZO-1/Tjp1 (P39447). Reason: Generic protein binding is uninformative. For Psen1 and MT1-MMP Dll1 is the protease substrate; the other interactions do not define a specific Dll1 molecular function. Removal does not dispute the reported interactions. Supporting Evidence: PMID:12794186 We then show that Dll1 is part of a high-molecular-weight complex containing presenilin1 and undergoes further cleavage by a gamma-secretase-like activity |
| GO:0005515 protein binding | IPI PMID:16000382 Mind bomb 1 is essential for generating functional Notch lig... | MODIFY | Summary: IPI with the E3 ubiquitin ligases Mib1 (Q80SY4), Neurl1 (Q923S6) and Neurl1b (Q0MW30/A8MQ27), which ubiquitinate the Dll1 cytoplasmic tail. Reason: Generic protein binding; these interactions are with E3 ligases for which Dll1 is the substrate, captured as ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:16000382 Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. PMID:17003037 Neuralized-2 (Neur2), which is a ubiquitin-protein isopeptide ligase (E3) that interacts with and ubiquitinates Delta. |
| GO:0005515 protein binding | IPI PMID:17003037 Neuralized-2 regulates a Notch ligand in cooperation with Mi... | MODIFY | Summary: IPI with the E3 ubiquitin ligases Mib1 (Q80SY4), Neurl1 (Q923S6) and Neurl1b (Q0MW30/A8MQ27), which ubiquitinate the Dll1 cytoplasmic tail. Reason: Generic protein binding; these interactions are with E3 ligases for which Dll1 is the substrate, captured as ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:16000382 Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. PMID:17003037 Neuralized-2 (Neur2), which is a ubiquitin-protein isopeptide ligase (E3) that interacts with and ubiquitinates Delta. |
| GO:0005515 protein binding | IPI PMID:19723503 Neuralized-2: expression in human and rodents and interactio... | MODIFY | Summary: IPI with the E3 ubiquitin ligases Mib1 (Q80SY4), Neurl1 (Q923S6) and Neurl1b (Q0MW30/A8MQ27), which ubiquitinate the Dll1 cytoplasmic tail. Reason: Generic protein binding; these interactions are with E3 ligases for which Dll1 is the substrate, captured as ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:16000382 Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. PMID:17003037 Neuralized-2 (Neur2), which is a ubiquitin-protein isopeptide ligase (E3) that interacts with and ubiquitinates Delta. |
| GO:0005515 protein binding | IPI PMID:19723503 Neuralized-2: expression in human and rodents and interactio... | MODIFY | Summary: IPI with the E3 ubiquitin ligases Mib1 (Q80SY4), Neurl1 (Q923S6) and Neurl1b (Q0MW30/A8MQ27), which ubiquitinate the Dll1 cytoplasmic tail. Reason: Generic protein binding; these interactions are with E3 ligases for which Dll1 is the substrate, captured as ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:16000382 Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. PMID:17003037 Neuralized-2 (Neur2), which is a ubiquitin-protein isopeptide ligase (E3) that interacts with and ubiquitinates Delta. |
| GO:0005515 protein binding | IPI PMID:21572390 MT1-MMP cleaves Dll1 to negatively regulate Notch signalling... | REMOVE | Summary: IPI with Psen1 (P49769; Dll1 is a gamma-secretase substrate), MT1-MMP/Mmp14 (P50281; Dll1 is cleaved by it), MAGP-2/Mfap5 (Q9QZJ6) and ZO-1/Tjp1 (P39447). Reason: Generic protein binding is uninformative. For Psen1 and MT1-MMP Dll1 is the protease substrate; the other interactions do not define a specific Dll1 molecular function. Removal does not dispute the reported interactions. Supporting Evidence: PMID:12794186 We then show that Dll1 is part of a high-molecular-weight complex containing presenilin1 and undergoes further cleavage by a gamma-secretase-like activity |
| GO:0005515 protein binding | IPI PMID:21985982 Delta-like 1-Lysine613 regulates notch signaling. | MODIFY | Summary: IPI with the E3 ubiquitin ligases Mib1 (Q80SY4), Neurl1 (Q923S6) and Neurl1b (Q0MW30/A8MQ27), which ubiquitinate the Dll1 cytoplasmic tail. Reason: Generic protein binding; these interactions are with E3 ligases for which Dll1 is the substrate, captured as ubiquitin protein ligase binding. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:16000382 Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. PMID:17003037 Neuralized-2 (Neur2), which is a ubiquitin-protein isopeptide ligase (E3) that interacts with and ubiquitinates Delta. |
| GO:0005515 protein binding | IPI PMID:24025447 Synaptojanin-2 binding protein stabilizes the Notch ligands ... | MODIFY | Summary: IPI with the PDZ-domain MAGUK protein Magi2/Acvrinp1 (Q9WVQ1), via the Dll1 C-terminal PDZ-binding motif. Reason: Generic protein binding; the interaction is PDZ-mediated. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:14529612 We delimited the fourth PDZ domain of Acvrinp1 and the PDZ-binding domain of Dll1 as major interacting domains. |
| GO:0005515 protein binding | IPI PMID:24715457 Cadherin-based adhesions in the apical endfoot are required ... | REMOVE | Summary: IPI with Psen1 (P49769; Dll1 is a gamma-secretase substrate), MT1-MMP/Mmp14 (P50281; Dll1 is cleaved by it), MAGP-2/Mfap5 (Q9QZJ6) and ZO-1/Tjp1 (P39447). Reason: Generic protein binding is uninformative. For Psen1 and MT1-MMP Dll1 is the protease substrate; the other interactions do not define a specific Dll1 molecular function. Removal does not dispute the reported interactions. Supporting Evidence: PMID:12794186 We then show that Dll1 is part of a high-molecular-weight complex containing presenilin1 and undergoes further cleavage by a gamma-secretase-like activity |
| GO:0005634 nucleus | EXP PMID:12794186 The Notch ligand Delta1 is sequentially cleaved by an ADAM p... | KEEP AS NON CORE | Summary: The Dll1 intracellular domain released by gamma-secretase localises in part to the nucleus. Reason: Supported for the cleaved ICD fragment, but the physiological nuclear function of the Dll1 ICD is not established; the ligand acts at the plasma membrane. Supporting Evidence: PMID:12794186 releasing the intracellular domain that localizes in part to the nucleus. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The Dll1 intracellular domain released by gamma-secretase localises in part to the nucleus. Reason: Supported for the cleaved ICD fragment, but the physiological nuclear function of the Dll1 ICD is not established; the ligand acts at the plasma membrane. Supporting Evidence: PMID:12794186 releasing the intracellular domain that localizes in part to the nucleus. |
| GO:0005886 plasma membrane | EXP PMID:12794186 The Notch ligand Delta1 is sequentially cleaved by an ADAM p... | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | IDA PMID:16000382 Mind bomb 1 is essential for generating functional Notch lig... | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2060798 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-2193065 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-9012873 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-9023350 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-9793915 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-9825286 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005886 plasma membrane | TAS Reactome:R-MMU-9832194 | ACCEPT | Summary: Dll1 is presented at the plasma membrane of signal-sending cells. Reason: Core location of ligand activity. Supporting Evidence: PMID:16000382 in the Mib1-/- mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types |
| GO:0005911 cell-cell junction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Dll1 localises at adherens junctions of apical endfeet/termini of neural progenitor processes, recruited by MAGI1. Reason: Supported specialised membrane subdomain; not required for ligand activity per se. Supporting Evidence: PMID:24715457 Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet PMID:15908431 Dll1 was recruited to these AJs through binding to MAGI1. |
| GO:0005912 adherens junction | IDA PMID:15908431 MAGI1 recruits Dll1 to cadherin-based adherens junctions and... | KEEP AS NON CORE | Summary: Dll1 localises at adherens junctions of apical endfeet/termini of neural progenitor processes, recruited by MAGI1. Reason: Supported specialised membrane subdomain; not required for ligand activity per se. Supporting Evidence: PMID:24715457 Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet PMID:15908431 Dll1 was recruited to these AJs through binding to MAGI1. |
| GO:0005912 adherens junction | IDA PMID:24715457 Cadherin-based adhesions in the apical endfoot are required ... | KEEP AS NON CORE | Summary: Dll1 localises at adherens junctions of apical endfeet/termini of neural progenitor processes, recruited by MAGI1. Reason: Supported specialised membrane subdomain; not required for ligand activity per se. Supporting Evidence: PMID:24715457 Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet PMID:15908431 Dll1 was recruited to these AJs through binding to MAGI1. |
| GO:0005912 adherens junction | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Dll1 localises at adherens junctions of apical endfeet/termini of neural progenitor processes, recruited by MAGI1. Reason: Supported specialised membrane subdomain; not required for ligand activity per se. Supporting Evidence: PMID:24715457 Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet PMID:15908431 Dll1 was recruited to these AJs through binding to MAGI1. |
| GO:0007154 cell communication | IEA GO_REF:0000002 | ACCEPT | Summary: Dll1 mediates juxtacrine cell-cell signalling via Notch. Reason: Correct, general description of the ligand role. Supporting Evidence: PMID:16621992 The block in myelopoiesis is the direct result of Notch signaling within the hemopoietic progenitor |
| GO:0007219 Notch signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Dll1 is an activating ligand of canonical Notch signalling. Reason: Core process. Supporting Evidence: PMID:19144989 DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. PMID:12730124 Dll1-mediated Notch signaling is essential for generation of left-right asymmetry |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Dll1 is an activating ligand of canonical Notch signalling. Reason: Core process. Supporting Evidence: PMID:19144989 DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. PMID:12730124 Dll1-mediated Notch signaling is essential for generation of left-right asymmetry |
| GO:0007219 Notch signaling pathway | IEP PMID:23688253 Delta-like 1 regulates Bergmann glial monolayer formation du... | ACCEPT | Summary: Dll1 is an activating ligand of canonical Notch signalling. Reason: Core process. Supporting Evidence: PMID:19144989 DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. PMID:12730124 Dll1-mediated Notch signaling is essential for generation of left-right asymmetry |
| GO:0007219 Notch signaling pathway | IMP PMID:12730124 Notch signaling regulates left-right asymmetry determination... | ACCEPT | Summary: Dll1 is an activating ligand of canonical Notch signalling. Reason: Core process. Supporting Evidence: PMID:19144989 DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. PMID:12730124 Dll1-mediated Notch signaling is essential for generation of left-right asymmetry |
| GO:0007219 Notch signaling pathway | IMP PMID:19389377 Dll1 and Dll4 function sequentially in the retina and pV2 do... | ACCEPT | Summary: Dll1 is an activating ligand of canonical Notch signalling. Reason: Core process. Supporting Evidence: PMID:19144989 DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. PMID:12730124 Dll1-mediated Notch signaling is essential for generation of left-right asymmetry |
| GO:0007219 Notch signaling pathway | ISO GO_REF:0000119 | ACCEPT | Summary: Dll1 is an activating ligand of canonical Notch signalling. Reason: Core process. Supporting Evidence: PMID:19144989 DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. PMID:12730124 Dll1-mediated Notch signaling is essential for generation of left-right asymmetry |
| GO:0007219 Notch signaling pathway | TAS PMID:15821257 Segmental expression of Notch and Hairy genes in nephrogenes... | ACCEPT | Summary: Dll1 is an activating ligand of canonical Notch signalling. Reason: Core process. Supporting Evidence: PMID:19144989 DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. PMID:12730124 Dll1-mediated Notch signaling is essential for generation of left-right asymmetry |
| GO:0007267 cell-cell signaling | IDA PMID:16621992 Notch signaling requires GATA-2 to inhibit myelopoiesis from... | ACCEPT | Summary: Dll1 mediates juxtacrine cell-cell signalling via Notch. Reason: Correct, general description of the ligand role. Supporting Evidence: PMID:16621992 The block in myelopoiesis is the direct result of Notch signaling within the hemopoietic progenitor |
| GO:0007368 determination of left/right symmetry | IMP PMID:12730124 Notch signaling regulates left-right asymmetry determination... | KEEP AS NON CORE | Summary: Dll1 mutants have left-right asymmetry defects owing to loss of Notch-induced Nodal at the node. Reason: Specific developmental outcome of Dll1-Notch signalling. Supporting Evidence: PMID:12730124 Embryos mutant for the Notch ligand Dll1 or doubly mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry. |
| GO:0007386 compartment pattern specification | IMP PMID:12001066 Segmentation defects of Notch pathway mutants and absence of... | KEEP AS NON CORE | Summary: Dll1 is required for somite formation, segmentation clock synchrony and somite polarity. Reason: Well-supported in vivo requirement as the PSM Notch ligand, but a tissue-specific outcome of its ligand function. Supporting Evidence: PMID:12001066 distinct segmentation defects are displayed in embryos mutant for the Notch pathway genes Notch1, Lunatic fringe (Lfng), Delta-like 1 (Dll1), and Delta-like 3 (Dll3). |
| GO:0007399 nervous system development | NAS PMID:10473134 Expression of the mouse Delta1 gene during organogenesis and... | KEEP AS NON CORE | Summary: NAS from expression studies of Dll1 during organogenesis and in the inner ear. Reason: Broadly consistent with functional data (Dll1 null embryos die mid-gestation; conditional loss affects neurogenesis and hair cell patterning), but these are pleiotropic consequences of Notch activation rather than distinct Dll1 functions. |
| GO:0008217 regulation of blood pressure | IMP PMID:19562077 Dll1 haploinsufficiency in adult mice leads to a complex phe... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:22096075 Ptf1a-mediated control of Dll1 reveals an alternative to the... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0008285 negative regulation of cell population proliferation | IMP PMID:17960184 Role of the Notch ligand Delta1 in embryonic and adult mouse... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0009792 embryo development ending in birth or egg hatching | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0009887 animal organ morphogenesis | NAS PMID:10473134 Expression of the mouse Delta1 gene during organogenesis and... | KEEP AS NON CORE | Summary: NAS from expression studies of Dll1 during organogenesis and in the inner ear. Reason: Broadly consistent with functional data (Dll1 null embryos die mid-gestation; conditional loss affects neurogenesis and hair cell patterning), but these are pleiotropic consequences of Notch activation rather than distinct Dll1 functions. |
| GO:0009912 auditory receptor cell fate commitment | NAS PMID:10473135 Expression of Delta1 and Serrate1 (Jagged1) in the mouse inn... | KEEP AS NON CORE | Summary: NAS from expression studies of Dll1 during organogenesis and in the inner ear. Reason: Broadly consistent with functional data (Dll1 null embryos die mid-gestation; conditional loss affects neurogenesis and hair cell patterning), but these are pleiotropic consequences of Notch activation rather than distinct Dll1 functions. |
| GO:0009912 auditory receptor cell fate commitment | NAS PMID:10704388 Notch signalling is required for cyclic expression of the ha... | KEEP AS NON CORE | Summary: NAS from expression studies of Dll1 during organogenesis and in the inner ear. Reason: Broadly consistent with functional data (Dll1 null embryos die mid-gestation; conditional loss affects neurogenesis and hair cell patterning), but these are pleiotropic consequences of Notch activation rather than distinct Dll1 functions. |
| GO:0009954 proximal/distal pattern formation | IMP PMID:22529374 Mind bomb 1 is required for pancreatic Ξ²-cell formation. | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0010628 positive regulation of gene expression | IMP PMID:11076679 Oscillating expression of c-Hey2 in the presomitic mesoderm ... | KEEP AS NON CORE | Summary: Loss of Dll1 reduces Notch target gene expression (e.g. Nodal, Hey2) in vivo. Reason: Indirect: Dll1 activates Notch at the membrane; transcriptional effects are mediated by NICD-RBP-J downstream. Supporting Evidence: PMID:12730124 the Notch pathway acts upstream of Nodal expression during left-right asymmetry determination in mice. |
| GO:0010628 positive regulation of gene expression | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Loss of Dll1 reduces Notch target gene expression (e.g. Nodal, Hey2) in vivo. Reason: Indirect: Dll1 activates Notch at the membrane; transcriptional effects are mediated by NICD-RBP-J downstream. Supporting Evidence: PMID:12730124 the Notch pathway acts upstream of Nodal expression during left-right asymmetry determination in mice. |
| GO:0014002 astrocyte development | IMP PMID:23688253 Delta-like 1 regulates Bergmann glial monolayer formation du... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0014807 regulation of somitogenesis | IMP PMID:26114479 Context-Dependent Functional Divergence of the Notch Ligands... | KEEP AS NON CORE | Summary: Dll1 is required for somite formation, segmentation clock synchrony and somite polarity. Reason: Well-supported in vivo requirement as the PSM Notch ligand, but a tissue-specific outcome of its ligand function. Supporting Evidence: PMID:12001066 distinct segmentation defects are displayed in embryos mutant for the Notch pathway genes Notch1, Lunatic fringe (Lfng), Delta-like 1 (Dll1), and Delta-like 3 (Dll3). |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane (single-pass type I). Reason: Correct. |
| GO:0016324 apical plasma membrane | IDA PMID:24715457 Cadherin-based adhesions in the apical endfoot are required ... | KEEP AS NON CORE | Summary: Dll1 localises at adherens junctions of apical endfeet/termini of neural progenitor processes, recruited by MAGI1. Reason: Supported specialised membrane subdomain; not required for ligand activity per se. Supporting Evidence: PMID:24715457 Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet PMID:15908431 Dll1 was recruited to these AJs through binding to MAGI1. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Dll1 localises at adherens junctions of apical endfeet/termini of neural progenitor processes, recruited by MAGI1. Reason: Supported specialised membrane subdomain; not required for ligand activity per se. Supporting Evidence: PMID:24715457 Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet PMID:15908431 Dll1 was recruited to these AJs through binding to MAGI1. |
| GO:0021510 spinal cord development | IMP PMID:19389377 Dll1 and Dll4 function sequentially in the retina and pV2 do... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0021688 cerebellar molecular layer formation | IMP PMID:23688253 Delta-like 1 regulates Bergmann glial monolayer formation du... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0021693 cerebellar Purkinje cell layer structural organization | IMP PMID:23688253 Delta-like 1 regulates Bergmann glial monolayer formation du... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0030155 regulation of cell adhesion | IMP PMID:22940113 Colonization of the satellite cell niche by skeletal muscle ... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0030182 neuron differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0030857 negative regulation of epithelial cell differentiation | IMP PMID:21915337 Delta1 expression, cell cycle exit, and commitment to a spec... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0030947 regulation of vascular endothelial growth factor receptor signaling pathway | IMP PMID:19144989 DLL1-mediated Notch activation regulates endothelial identit... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0030957 Tat protein binding | IEA GO_REF:0000107 | MODIFY | Summary: Tat protein binding transferred from human DLL1, whose source annotation is an IPI to PMID:15509766 (Wright et al. 2004), a study of Delta binding to the PDZ4 domain of the MAGI1/2/3 scaffolds, not of HIV-1 Tat. Reason: Harmonised with the human DLL1 review, which MODIFYs the source IPI to PDZ domain binding because the cited experiment shows the Delta C-terminal motif binding MAGI PDZ4; 'Tat protein binding' does not describe that experiment. The C-terminal PDZ-binding motif is conserved in mouse Dll1, and mouse Dll1 binding to the PDZ protein Magi2 is separately annotated here (protein binding IPIs modified to PDZ domain binding), so the transferred annotation is corrected to PDZ domain binding rather than removed. Non-core. Propagation Review Root cause: SOURCE BAD Failure modes: SOURCE MISCITATION Sources checked: UniProtKB:O00548 Β· DLL1 SOURCE BAD The human DLL1 source IPI (PMID:15509766) describes Delta binding to MAGI PDZ4, not HIV-1 Tat; the human DLL1 review MODIFYs it to PDZ domain binding, and the transferred term is corrected the same way here. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:15509766 We show that these Deltas associate with the membrane-associated scaffolding proteins MAGI1, MAGI2 and MAGI3, through a direct interaction between the C termini of the Deltas and a specific PDZ domain (PDZ4) of the MAGIs. |
| GO:0030957 Tat protein binding | ISO GO_REF:0000119 | MODIFY | Summary: Tat protein binding transferred from human DLL1, whose source annotation is an IPI to PMID:15509766 (Wright et al. 2004), a study of Delta binding to the PDZ4 domain of the MAGI1/2/3 scaffolds, not of HIV-1 Tat. Reason: Harmonised with the human DLL1 review, which MODIFYs the source IPI to PDZ domain binding because the cited experiment shows the Delta C-terminal motif binding MAGI PDZ4; 'Tat protein binding' does not describe that experiment. The C-terminal PDZ-binding motif is conserved in mouse Dll1, and mouse Dll1 binding to the PDZ protein Magi2 is separately annotated here (protein binding IPIs modified to PDZ domain binding), so the transferred annotation is corrected to PDZ domain binding rather than removed. Non-core. Propagation Review Root cause: SOURCE BAD Failure modes: SOURCE MISCITATION Sources checked: UniProtKB:O00548 Β· DLL1 SOURCE BAD The human DLL1 source IPI (PMID:15509766) describes Delta binding to MAGI PDZ4, not HIV-1 Tat; the human DLL1 review MODIFYs it to PDZ domain binding, and the transferred term is corrected the same way here. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:15509766 We show that these Deltas associate with the membrane-associated scaffolding proteins MAGI1, MAGI2 and MAGI3, through a direct interaction between the C termini of the Deltas and a specific PDZ domain (PDZ4) of the MAGIs. |
| GO:0031410 cytoplasmic vesicle | IDA PMID:16000382 Mind bomb 1 is essential for generating functional Notch lig... | KEEP AS NON CORE | Summary: Endocytosed Dll1 in cytoplasmic vesicles, dependent on Mib1. Reason: Reflects ligand endocytosis/recycling, part of the activation mechanism; non-core location. Supporting Evidence: PMID:16000382 indicating that Mib1 is essential for the endocytosis of Notch ligand. |
| GO:0032693 negative regulation of interleukin-10 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0032693 negative regulation of interleukin-10 production | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0034351 negative regulation of glial cell apoptotic process | IMP PMID:23688253 Delta-like 1 regulates Bergmann glial monolayer formation du... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0035265 organ growth | IMP PMID:22096075 Ptf1a-mediated control of Dll1 reveals an alternative to the... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0040008 regulation of growth | IMP PMID:19562077 Dll1 haploinsufficiency in adult mice leads to a complex phe... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0042472 inner ear morphogenesis | NAS PMID:9858718 Distinct expression patterns of notch family receptors and l... | KEEP AS NON CORE | Summary: NAS from expression studies of Dll1 during organogenesis and in the inner ear. Reason: Broadly consistent with functional data (Dll1 null embryos die mid-gestation; conditional loss affects neurogenesis and hair cell patterning), but these are pleiotropic consequences of Notch activation rather than distinct Dll1 functions. |
| GO:0042475 odontogenesis of dentin-containing tooth | NAS PMID:9882480 Delta-notch signaling in odontogenesis: correlation with cyt... | MARK AS OVER ANNOTATED | Summary: NAS from expression correlation of Delta/Notch genes with tooth cytodifferentiation. Reason: Expression-based statement without functional evidence for Dll1 in odontogenesis. |
| GO:0042491 inner ear auditory receptor cell differentiation | NAS PMID:9858718 Distinct expression patterns of notch family receptors and l... | KEEP AS NON CORE | Summary: NAS from expression studies of Dll1 during organogenesis and in the inner ear. Reason: Broadly consistent with functional data (Dll1 null embryos die mid-gestation; conditional loss affects neurogenesis and hair cell patterning), but these are pleiotropic consequences of Notch activation rather than distinct Dll1 functions. |
| GO:0045121 membrane raft | IDA PMID:18676613 The intracellular region of Notch ligands Dll1 and Dll3 regu... | KEEP AS NON CORE | Summary: Dll1 associates with lipid rafts; K613R mutant has increased raft retention. Reason: Supported membrane microdomain localisation; non-core. Supporting Evidence: PMID:21985982 did enhance the fraction associated with lipid rafts. |
| GO:0045121 membrane raft | IDA PMID:21985982 Delta-like 1-Lysine613 regulates notch signaling. | KEEP AS NON CORE | Summary: Dll1 associates with lipid rafts; K613R mutant has increased raft retention. Reason: Supported membrane microdomain localisation; non-core. Supporting Evidence: PMID:21985982 did enhance the fraction associated with lipid rafts. |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Dll1 associates with lipid rafts; K613R mutant has increased raft retention. Reason: Supported membrane microdomain localisation; non-core. Supporting Evidence: PMID:21985982 did enhance the fraction associated with lipid rafts. |
| GO:0045165 cell fate commitment | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0045596 negative regulation of cell differentiation | IMP PMID:10476967 Notch signalling controls pancreatic cell differentiation. | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045596 negative regulation of cell differentiation | IMP PMID:16495313 Notch ligands with contrasting functions: Jagged1 and Delta1... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045596 negative regulation of cell differentiation | IMP PMID:21238454 Dll1- and dll4-mediated notch signaling are required for hom... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045605 negative regulation of epidermal cell differentiation | IMP PMID:17960184 Role of the Notch ligand Delta1 in embryonic and adult mouse... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045608 negative regulation of inner ear auditory receptor cell differentiation | IMP PMID:16495313 Notch ligands with contrasting functions: Jagged1 and Delta1... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045638 negative regulation of myeloid cell differentiation | IDA PMID:16621992 Notch signaling requires GATA-2 to inhibit myelopoiesis from... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045662 negative regulation of myoblast differentiation | IMP PMID:17194759 Premature myogenic differentiation and depletion of progenit... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045665 negative regulation of neuron differentiation | IMP PMID:19389377 Dll1 and Dll4 function sequentially in the retina and pV2 do... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045665 negative regulation of neuron differentiation | IMP PMID:20081190 Domain-specific control of neurogenesis achieved through pat... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0045746 negative regulation of Notch signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA (PANTHER:PTN001170801) negative regulation of Notch signaling pathway, reflecting ligand cis-inhibition in the family. Reason: DSL ligands including Dll1 can cis-inhibit Notch in the same cell; this is a genuine but secondary aspect of Dll1 function relative to trans-activation. Supporting Evidence: file:mouse/Dll1/Dll1-deep-research-falcon.md Dll1 also mediates cis-inhibition when present in the same cell as Notch |
| GO:0045747 positive regulation of Notch signaling pathway | IDA PMID:10958687 Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly in... | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045747 positive regulation of Notch signaling pathway | IDA PMID:15574878 Fringe glycosyltransferases differentially modulate Notch1 p... | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045747 positive regulation of Notch signaling pathway | IDA PMID:18676613 The intracellular region of Notch ligands Dll1 and Dll3 regu... | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045747 positive regulation of Notch signaling pathway | IDA PMID:26114479 Context-Dependent Functional Divergence of the Notch Ligands... | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045747 positive regulation of Notch signaling pathway | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045747 positive regulation of Notch signaling pathway | IMP PMID:19144989 DLL1-mediated Notch activation regulates endothelial identit... | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045747 positive regulation of Notch signaling pathway | IMP PMID:19389377 Dll1 and Dll4 function sequentially in the retina and pV2 do... | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045747 positive regulation of Notch signaling pathway | IMP PMID:21915337 Delta1 expression, cell cycle exit, and commitment to a spec... | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045747 positive regulation of Notch signaling pathway | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Dll1 binding activates Notch cleavage and target transcription. Reason: Correct (Dll1 trans-activation of Notch is directly supported by receptor activation assays and in vivo genetics), but as the activating ligand Dll1 is a participant in the Notch signaling pathway itself (GO:0007219, accepted as the core process) rather than a regulator of it, so this regulation term is retained as non-core. Harmonised with the human DLL1 review, which treats the same term as KEEP_AS_NON_CORE for the same reason. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0045807 positive regulation of endocytosis | IDA PMID:18676613 The intracellular region of Notch ligands Dll1 and Dll3 regu... | KEEP AS NON CORE | Summary: Ubiquitinated, recycled Dll1 induces transendocytosis of the Notch1 extracellular domain into the ligand cell. Reason: Mechanistic component of ligand activation; non-core. Supporting Evidence: PMID:18676613 is endocytosed, recycled, and interacts with Notch1 but is unable to induce transendocytosis of the extracellular region of Notch1 or to signal. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:12730124 Notch signaling regulates left-right asymmetry determination... | KEEP AS NON CORE | Summary: Loss of Dll1 reduces Notch target gene expression (e.g. Nodal, Hey2) in vivo. Reason: Indirect: Dll1 activates Notch at the membrane; transcriptional effects are mediated by NICD-RBP-J downstream. Supporting Evidence: PMID:12730124 the Notch pathway acts upstream of Nodal expression during left-right asymmetry determination in mice. |
| GO:0046331 lateral inhibition | IDA PMID:18997111 Selection of differentiating cells by different levels of de... | ACCEPT | Summary: Dll1 mediates lateral inhibition in neural precursors, inner ear and intestine. Reason: Lateral inhibition is the canonical developmental process executed by Delta ligands; directly supported by mosaic Dll1 deletion and expression dynamics. Supporting Evidence: PMID:18997111 different levels of Dll1 expression determine the fate of NPCs through cell-cell interactions, most likely through the Notch-Delta lateral inhibitory signaling pathway PMID:16495313 In the absence of Dll1, auditory hair cells develop early and in excess, in agreement with the lateral inhibition hypothesis. |
| GO:0046331 lateral inhibition | IMP PMID:21915337 Delta1 expression, cell cycle exit, and commitment to a spec... | ACCEPT | Summary: Dll1 mediates lateral inhibition in neural precursors, inner ear and intestine. Reason: Lateral inhibition is the canonical developmental process executed by Delta ligands; directly supported by mosaic Dll1 deletion and expression dynamics. Supporting Evidence: PMID:18997111 different levels of Dll1 expression determine the fate of NPCs through cell-cell interactions, most likely through the Notch-Delta lateral inhibitory signaling pathway PMID:16495313 In the absence of Dll1, auditory hair cells develop early and in excess, in agreement with the lateral inhibition hypothesis. |
| GO:0048018 receptor ligand activity | IEA GO_REF:0000107 | ACCEPT | Summary: Receptor ligand activity (ISO/IEA from human DLL1). Reason: Dll1 binds Notch and activates receptor cleavage and RBP-J-dependent transcription, i.e. it is an activating ligand of the Notch receptor; core MF. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0048018 receptor ligand activity | ISO GO_REF:0000119 | ACCEPT | Summary: Receptor ligand activity (ISO/IEA from human DLL1). Reason: Dll1 binds Notch and activates receptor cleavage and RBP-J-dependent transcription, i.e. it is an activating ligand of the Notch receptor; core MF. Supporting Evidence: PMID:10958687 binding of DSL proteins to Notch2 also activated the transcription of reporter genes driven by the RBP-Jkappa-responsive promoter. |
| GO:0048592 eye morphogenesis | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Broad ARBA machine-learning process term. Reason: Too vague or not specifically supported for Dll1; adds no informative content. |
| GO:0048598 embryonic morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0048630 skeletal muscle tissue growth | IMP PMID:22940113 Colonization of the satellite cell niche by skeletal muscle ... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0048631 regulation of skeletal muscle tissue growth | IMP PMID:17194759 Premature myogenic differentiation and depletion of progenit... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0048633 positive regulation of skeletal muscle tissue growth | IMP PMID:25220152 Divergent and conserved roles of Dll1 signaling in developme... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0048638 regulation of developmental growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0048665 neuron fate specification | IDA PMID:18997111 Selection of differentiating cells by different levels of de... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0048839 inner ear development | IMP PMID:16495313 Notch ligands with contrasting functions: Jagged1 and Delta1... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0048871 multicellular organismal-level homeostasis | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Broad ARBA machine-learning process term. Reason: Too vague or not specifically supported for Dll1; adds no informative content. |
| GO:0050767 regulation of neurogenesis | IMP PMID:18997111 Selection of differentiating cells by different levels of de... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0050767 regulation of neurogenesis | IMP PMID:19389377 Dll1 and Dll4 function sequentially in the retina and pV2 do... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0051049 regulation of transport | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Broad ARBA machine-learning process term. Reason: Too vague or not specifically supported for Dll1; adds no informative content. |
| GO:0051093 negative regulation of developmental process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0051241 negative regulation of multicellular organismal process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Broad ARBA machine-learning process term. Reason: Too vague or not specifically supported for Dll1; adds no informative content. |
| GO:0051302 regulation of cell division | IMP PMID:21915337 Delta1 expression, cell cycle exit, and commitment to a spec... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0060041 retina development in camera-type eye | IMP PMID:19389377 Dll1 and Dll4 function sequentially in the retina and pV2 do... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0060042 retina morphogenesis in camera-type eye | IMP PMID:19389377 Dll1 and Dll4 function sequentially in the retina and pV2 do... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0060562 epithelial tube morphogenesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0060853 Notch signaling pathway involved in arterial endothelial cell fate commitment | IMP PMID:19144989 DLL1-mediated Notch activation regulates endothelial identit... | ACCEPT | Summary: DLL1 activates Notch1 in fetal arterial endothelium to maintain arterial identity. Reason: Specific Notch signalling process in which Dll1 is the ligand. Supporting Evidence: PMID:19144989 DLL1 is an essential Notch ligand in the vascular endothelium of large arteries to activate Notch1 and maintain arterial identity. |
| GO:0061326 renal tubule development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Broad ARBA developmental process term. Reason: Generally consistent with Dll1's pleiotropic developmental requirements via Notch signalling, but non-specific. |
| GO:0070986 left/right axis specification | IMP PMID:12730124 Notch signaling regulates left-right asymmetry determination... | KEEP AS NON CORE | Summary: Dll1 mutants have left-right asymmetry defects owing to loss of Notch-induced Nodal at the node. Reason: Specific developmental outcome of Dll1-Notch signalling. Supporting Evidence: PMID:12730124 Embryos mutant for the Notch ligand Dll1 or doubly mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry. |
| GO:0072006 nephron development | IMP PMID:23806616 The extracellular domain of Notch2 increases its cell-surfac... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0072014 proximal tubule development | IEP PMID:15821257 Segmental expression of Notch and Hairy genes in nephrogenes... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0072070 loop of Henle development | IEP PMID:15821257 Segmental expression of Notch and Hairy genes in nephrogenes... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0072583 clathrin-dependent endocytosis | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Clathrin-dependent endocytosis (ISO from rat / ISS). Reason: Dll1 is endocytosed as cargo (driven by Mib1 ubiquitination); being internalised does not mean Dll1 performs the endocytic process. The ligand-activation role is captured by Notch signalling terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:70949 SUPPORTS SOURCE BUT NOT TARGET Rat Dll1 source reflects ligand internalisation as cargo; cargo does not execute the endocytic process. UniProtKB:P97677 SUPPORTS SOURCE BUT NOT TARGET Same cargo-versus-machinery issue for the ISS source. |
| GO:0072583 clathrin-dependent endocytosis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Clathrin-dependent endocytosis (ISO from rat / ISS). Reason: Dll1 is endocytosed as cargo (driven by Mib1 ubiquitination); being internalised does not mean Dll1 performs the endocytic process. The ligand-activation role is captured by Notch signalling terms. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:70949 SUPPORTS SOURCE BUT NOT TARGET Rat Dll1 source reflects ligand internalisation as cargo; cargo does not execute the endocytic process. UniProtKB:P97677 SUPPORTS SOURCE BUT NOT TARGET Same cargo-versus-machinery issue for the ISS source. |
| GO:0097009 energy homeostasis | IMP PMID:19562077 Dll1 haploinsufficiency in adult mice leads to a complex phe... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0097102 endothelial tip cell fate specification | IMP PMID:22282195 Extrinsic Notch ligand Delta-like 1 regulates tip cell selec... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0097110 scaffold protein binding | IPI PMID:15908431 MAGI1 recruits Dll1 to cadherin-based adherens junctions and... | KEEP AS NON CORE | Summary: Dll1 binds the scaffold protein MAGI1, which recruits it to adherens junctions. Reason: Experimentally supported interaction that localises and stabilises Dll1; accessory to its core ligand function. Supporting Evidence: PMID:15908431 Dll1 was recruited to these AJs through binding to MAGI1. |
| GO:0097150 neuronal stem cell population maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0097150 neuronal stem cell population maintenance | IMP PMID:23695674 Dll1 maintains quiescence of adult neural stem cells and seg... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:0098773 skin epidermis development | IMP PMID:17960184 Role of the Notch ligand Delta1 in embryonic and adult mouse... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:1900746 regulation of vascular endothelial growth factor signaling pathway | IMP PMID:19144989 DLL1-mediated Notch activation regulates endothelial identit... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:1903672 positive regulation of sprouting angiogenesis | IMP PMID:22282195 Extrinsic Notch ligand Delta-like 1 regulates tip cell selec... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
| GO:2000726 negative regulation of cardiac muscle cell differentiation | IMP PMID:18371447 MicroRNA regulation of cell lineages in mouse and human embr... | KEEP AS NON CORE | Summary: Tissue-specific developmental, differentiation, proliferation or physiological outcome of Dll1 loss or gain of function (neural, retina, cerebellum, inner ear, intestine, skin, muscle, pancreas, kidney, vasculature, immune cells, adult homeostasis). Reason: Experimentally supported requirements that reflect Dll1's role as the activating Notch ligand in the relevant tissue; pleiotropic consequences rather than distinct functions. |
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Experiment: Knock in a Dll1 allele resistant to ADAM10/gamma-secretase processing and assess whether nuclear Dll1-ICD contributes to signal-sending-cell fate in neurogenesis.
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