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Delta-like protein 1 (Dll1), encoded by the Dll1 gene (UniProt accession Q61483), is a canonical transmembrane Notch ligand in Mus musculus (mouse). The protein is also known as Drosophila Delta homolog 1 or Delta1, confirming alignment with the specified UniProt entry. Dll1 belongs to the Delta/Serrate/LAG-2 (DSL) family of Notch ligands and contains the defining DSL domain along with eight epidermal growth factor (EGF)-like repeats in its extracellular region (tveriakhina2018theectodomainsdetermine pages 2-5, wang2011notchsignalingand pages 3-5, ladi2005thedivergentdsl pages 6-7).
Dll1 is synthesized as a type I single-pass transmembrane protein comprising an N-terminal extracellular region, a transmembrane helix, and a short cytoplasmic tail (tveriakhina2018theectodomainsdetermine pages 1-2, wang2011notchsignalingand pages 3-5). The detailed structural organization is presented in the following table:
| Structural feature | Position / organization | Principal function | Key structural and conservation features | Evidence |
|---|---|---|---|---|
| Signal peptide / precursor organization | N terminus; directs the nascent type-I membrane protein into the secretory pathway | Enables membrane insertion, extracellular-domain maturation, and delivery toward the cell surface | Consistent with DLL1 being synthesized as a precursor and subsequently displayed with its N terminus extracellular and short C terminus cytoplasmic | (wang2011notchsignalingand pages 3-5, geffers2007divergentfunctionsand pages 6-8) |
| C2 domain, also termed MNNL | N-terminal extracellular module preceding the DSL domain | Contributes to high-affinity Notch recognition, ligand orientation, and possibly membrane association | Forms part of an extended C2–DSL–EGF architecture; contacts the receptor near Notch EGF12. Unlike Jagged-family C2 domains, Delta-family C2 domains do not bind calcium. “MNNL” and “C2” are overlapping nomenclatures used for this N-terminal module | (tveriakhina2018theectodomainsdetermine pages 2-5, handford2018structuralinsightsinto pages 6-9, handford2018structuralinsightsinto pages 21-23) |
| DSL domain | Extracellular; immediately follows C2/MNNL | Provides the defining canonical Notch-ligand interaction surface and is essential for productive trans-activation | Delta/Serrate/LAG-2-family signature domain; contacts Notch near EGF11. Conserved YY and GWxG features help stabilize its fold: disrupting GWxG abolishes activation, while tyrosine mutations strongly reduce activation and can impair surface delivery | (geffers2008biochemicalnonequivalenceof pages 87-90, cordle2008aconservedface pages 17-21) |
| EGF-like repeat array | Eight extracellular EGF-like repeats follow the DSL domain | Creates an elongated extracellular scaffold, supports receptor binding and productive signaling, and helps determine ligand-specific activity | Each canonical EGF-like module is about 40 residues and generally contains six cysteines forming three disulfide bonds. DLL1 has eight repeats, compared with six in divergent DLL3; some repeats contain calcium-binding or Asp/Asn-hydroxylation-associated motifs | (tveriakhina2018theectodomainsdetermine pages 2-5, wang2011notchsignalingand pages 3-5, ladi2005thedivergentdsl pages 6-7) |
| EGF repeats 1–2 and DOS motif | First two EGF repeats immediately C-terminal to DSL; DOS motif spans the EGF1–2 region | Acts with DSL as an additional Notch-binding module and enhances signal transmission | The Delta-and-OSM-11-like proteins (DOS) motif is present in DLL1 but absent from DLL4. Both DLL1-specific sequence and correct spacing of EGF1–2 are important: substitution or spacer disruption can abolish trans-activation even when membrane localization is retained | (hirano2020deltalike1and pages 8-9, geffers2007divergentfunctionsand pages 4-5, hirano2020deltalike1and pages 4-6) |
| N terminus through EGF3 | Composite C2/MNNL–DSL–EGF1–3 receptor-interaction region | Major determinant of receptor selectivity and ligand-specific signaling behavior | Domain-swap experiments localize much of the difference between DLL1 and DLL4 to this region. DLL1 activates NOTCH1 and NOTCH2 approximately equally in tested cell assays, whereas DLL4 preferentially activates NOTCH1 | (tveriakhina2018theectodomainsdetermine pages 1-2, tveriakhina2018theectodomainsdetermine pages 2-5) |
| Distal EGF repeats 4–8 | Membrane-proximal portion of the extracellular EGF array | Extends and positions the receptor-binding head and can contribute context-dependent structural support | DLL1 is nearly linear through its N-terminal domains but exhibits an approximately 90° bend between EGF4 and EGF5; interfaces among repeats can be rigid, flexible, or bent. Some distal repeats are more interchangeable with DLL3 than EGF1–2 | (handford2018structuralinsightsinto pages 6-9, geffers2007divergentfunctionsand pages 4-5) |
| Juxtamembrane ectodomain cleavage region | Extracellular, approximately 10 residues before the transmembrane segment; principal mouse site mapped near His535–Met536 | Substrate region for ADAM-mediated ectodomain shedding, producing soluble DLL1-EC and membrane-retained DLL1-TMIC | Cleavage depends on the local region rather than one invariant short motif. ADAM10 contributes physiologically, while ADAM9, ADAM12, and ADAM17 can also process DLL1 in cellular systems | (dyczynska2007proteolyticprocessingof pages 7-8, zolkiewska2008adamproteasesligand pages 4-6) |
| Transmembrane helix | Single membrane-spanning segment near the C terminus | Anchors full-length DLL1 at the signal-sending cell surface, permitting mechanically coupled, contact-dependent signaling | Establishes DLL1 as a type-I single-pass membrane protein; after ectodomain shedding, it remains within DLL1-TMIC and becomes a substrate for presenilin-dependent γ-secretase | (zolkiewska2008adamproteasesligand pages 8-9, zolkiewska2008adamproteasesligand pages 2-4) |
| Intracellular domain | Short cytoplasmic C-terminal tail | Controls ubiquitination, endocytosis, trafficking, clustering, and signaling competence of membrane-bound DLL1 | Contains numerous lysines—17 reported in mouse DLL1—as candidate ubiquitination sites and a conserved C-terminal PDZ-binding motif. Mindbomb/Neuralized-dependent ubiquitination and endocytosis help generate the pulling force required for Notch activation | (geffers2008biochemicalnonequivalenceof pages 90-93, geffers2008biochemicalnonequivalenceof pages 87-90, ladi2005thedivergentdsl pages 6-7) |
| Proteolytically derived intracellular domain, DLL1-IC | Released from DLL1-TMIC by γ-secretase after ADAM cleavage | Proposed reverse-signaling or cell-autonomous regulatory fragment; its physiological importance remains less certain than canonical forward signaling | Short-lived and rapidly degraded by the proteasome; γ-secretase inhibition causes DLL1-TMIC accumulation, demonstrating sequential ADAM-then-γ-secretase processing | (zolkiewska2008adamproteasesligand pages 8-9, dyczynska2007proteolyticprocessingof pages 4-5, dyczynska2007proteolyticprocessingof pages 3-4) |
Table: Domain-by-domain summary of mouse DLL1 (UniProt Q61483), linking its C2/MNNL, DSL, eight EGF repeats, DOS motif, membrane anchor, and cytoplasmic tail to receptor binding, trafficking, and proteolytic processing.
The extracellular domain begins with an N-terminal C2 domain (also termed the MNNL domain), which participates in receptor recognition and contacts Notch EGF repeat 12 (tveriakhina2018theectodomainsdetermine pages 2-5, handford2018structuralinsightsinto pages 6-9). Unlike Jagged-family ligands, the Delta-family C2 domains do not bind calcium (handford2018structuralinsightsinto pages 6-9, cordle2008aconservedface pages 17-21). Immediately following the C2/MNNL region is the DSL domain, the defining structural signature of Notch ligands, which contacts Notch EGF repeat 11 and provides the principal binding interface (tveriakhina2018theectodomainsdetermine pages 1-2, cordle2008aconservedface pages 17-21). Within the DSL domain, conserved tyrosine (YY) and GWxG motifs are critical for structural integrity: disrupting the GWxG motif abolishes Notch transactivation, while tyrosine mutations severely impair both activation and cell-surface delivery (geffers2008biochemicalnonequivalenceof pages 87-90).
The eight EGF-like repeats form an extended, nearly linear extracellular scaffold (handford2018structuralinsightsinto pages 6-9). The first two EGF repeats, together with the DSL domain, constitute the minimal functional unit for Notch activation; their correct sequence and spacing are essential, as disruption abolishes signaling (hirano2020deltalike1and pages 8-9, geffers2007divergentfunctionsand pages 4-5). Dll1 also contains a Delta-and-OSM-11-like (DOS) motif within the EGF1–2 region, which is present in Dll1 but absent from Dll4, and contributes to enhanced ligand activity (hirano2020deltalike1and pages 1-2, hirano2020deltalike1and pages 8-9). Domain-swap experiments demonstrate that the N-terminal C2/MNNL–DSL–EGF1–3 region largely determines ligand-specific signaling behavior: Dll1 activates NOTCH1 and NOTCH2 approximately equally, whereas Dll4 preferentially activates NOTCH1 (tveriakhina2018theectodomainsdetermine pages 1-2, tveriakhina2018theectodomainsdetermine pages 2-5).
The short intracellular domain contains numerous lysine residues (17 in mouse Dll1) that serve as ubiquitination sites and a conserved C-terminal PDZ-binding motif (geffers2008biochemicalnonequivalenceof pages 90-93, ladi2005thedivergentdsl pages 6-7). Ubiquitination by E3 ligases such as Mindbomb and Neuralized promotes ligand endocytosis, which is mechanistically required for productive Notch activation (geffers2008biochemicalnonequivalenceof pages 90-93, geffers2008biochemicalnonequivalenceof pages 14-17).
Dll1 functions as a membrane-bound Notch ligand that activates Notch receptors on adjacent cells through contact-dependent, trans-cellular signaling (hirano2020deltalike1and pages 1-2, tveriakhina2018theectodomainsdetermine pages 1-2). The molecular mechanism proceeds through several coordinated steps:
Dll1 on the signal-sending cell binds Notch receptors on a neighboring signal-receiving cell via its extracellular DSL and EGF-repeat regions (tveriakhina2018theectodomainsdetermine pages 1-2, wang2011notchsignalingand pages 3-5). The MNNL/C2 and DSL domains provide high-affinity contacts with Notch EGF repeats 12 and 11, respectively, while adjacent EGF repeats contribute to productive interaction (tveriakhina2018theectodomainsdetermine pages 2-5). This trans-interaction occurs in an antiparallel orientation that positions the two membranes in close apposition (vazquezulloa2022reversibleandbidirectional pages 7-8).
Following ligand–receptor binding, ubiquitination of the Dll1 intracellular domain by E3 ligases promotes endocytosis of the ligand-Notch complex by the signal-sending cell (geffers2008biochemicalnonequivalenceof pages 90-93, geffers2008biochemicalnonequivalenceof pages 14-17). This endocytic internalization generates a mechanical pulling force that physically dissociates the Notch heterodimer, exposing the receptor to proteolytic cleavage (geffers2008biochemicalnonequivalenceof pages 14-17, wang2011notchsignalingand pages 3-5). The requirement for ligand endocytosis distinguishes productive trans-activation from nonproductive cis-inhibition and explains why soluble or intracellular-domain-deficient ligands cannot fully activate Notch (geffers2008biochemicalnonequivalenceof pages 90-93, zolkiewska2008adamproteasesligand pages 6-8).
After ligand-induced conformational change, an ADAM metalloprotease—primarily ADAM10 under physiological conditions—cleaves Notch at the S2 site, releasing the Notch extracellular domain (geffers2008biochemicalnonequivalenceof pages 14-17, wang2011notchsignalingand pages 3-5). Subsequent γ-secretase-dependent intramembrane proteolysis at the S3 site releases the Notch intracellular domain (NICD) from the membrane (geffers2008biochemicalnonequivalenceof pages 14-17). NICD then translocates to the nucleus, where it associates with the CSL/RBPJ transcription factor and Mastermind-like coactivators to activate Notch target-gene expression (hirano2020deltalike1and pages 1-2, tveriakhina2018theectodomainsdetermine pages 1-2, geffers2008biochemicalnonequivalenceof pages 14-17).
Dll1 also mediates cis-inhibition when present in the same cell as Notch (geffers2008biochemicalnonequivalenceof pages 87-90, vazquezulloa2022reversibleandbidirectional pages 7-8, vazquezulloa2022reversibleandbidirectional pages 5-7). In this cell-autonomous interaction, Dll1 binds and sequesters Notch receptors, preventing them from responding to activating ligands on neighboring cells (vazquezulloa2022reversibleandbidirectional pages 7-8, vazquezulloa2022reversibleandbidirectional pages 5-7). Cis-inhibition can occur intracellularly and does not require a functional DSL domain or cell-surface presentation, distinguishing it mechanistically from trans-activation (geffers2008biochemicalnonequivalenceof pages 87-90, geffers2008biochemicalnonequivalenceof pages 75-78). This cis/trans regulatory balance helps establish directionality in Notch signaling and prevents autocrine activation (vazquezulloa2022reversibleandbidirectional pages 7-8, vazquezulloa2022reversibleandbidirectional pages 5-7).
As noted in the UniProt annotation, Dll1 exists in multiple processed forms:
The approximately 90-kDa full-length, membrane-anchored form represents the canonical ligand capable of trans-activating Notch (dyczynska2007proteolyticprocessingof pages 1-2, dyczynska2007proteolyticprocessingof pages 3-4).
ADAM metalloproteases, particularly ADAM9, ADAM10, ADAM12, and ADAM17, cleave Dll1 in its juxtamembrane extracellular region, approximately 10 amino acids from the transmembrane domain (dyczynska2007proteolyticprocessingof pages 7-8, zolkiewska2008adamproteasesligand pages 4-6). The principal cleavage site in mouse Dll1 has been mapped between His535 and Met536 (zolkiewska2008adamproteasesligand pages 4-6). This cleavage releases a soluble N-terminal extracellular fragment (Dll1-EC or NTF, approximately 60–65 kDa) into the extracellular medium (dyczynska2007proteolyticprocessingof pages 1-2, zolkiewska2008adamproteasesligand pages 2-4, dyczynska2007proteolyticprocessingof pages 4-5). ADAM10 is the primary physiological sheddase, though ADAM12-mediated processing has been extensively characterized in vitro (dyczynska2007proteolyticprocessingof pages 7-8, dyczynska2007proteolyticprocessingof pages 1-2, zolkiewska2008adamproteasesligand pages 4-6). Soluble Dll1 fragments do not activate Notch and can act as competitive inhibitors (klose2015solublenotchligand pages 5-7, zolkiewska2008adamproteasesligand pages 6-8).
ADAM cleavage leaves a membrane-associated C-terminal fragment (Dll1-TMIC, approximately 29 kDa) containing the transmembrane and intracellular domains (dyczynska2007proteolyticprocessingof pages 1-2, zolkiewska2008adamproteasesligand pages 8-9, zolkiewska2008adamproteasesligand pages 2-4). This intermediate fragment is a substrate for subsequent γ-secretase processing (zolkiewska2008adamproteasesligand pages 8-9, dyczynska2007proteolyticprocessingof pages 4-5).
Following ADAM cleavage, presenilin-dependent γ-secretase cleaves Dll1-TMIC, releasing an intracellular domain (Dll1-IC) of approximately 3 kDa smaller than the TMIC (zolkiewska2008adamproteasesligand pages 8-9, dyczynska2007proteolyticprocessingof pages 4-5). This fragment is rapidly degraded by the proteasome and is difficult to detect without proteasome inhibitors (dyczynska2007proteolyticprocessingof pages 4-5). The physiological significance of Dll1-IC remains less well understood than the canonical forward signaling mechanism, though it may participate in reverse or bidirectional signaling (zolkiewska2008adamproteasesligand pages 8-9, zolkiewska2008adamproteasesligand pages 2-4).
ADAM-mediated Dll1 processing is regulated: cleavage by ADAM12 is constitutive, cell-density-dependent, and occurs in cis orientation (dyczynska2007proteolyticprocessingof pages 1-2). Importantly, ADAM cleavage of Dll1 relieves cis-inhibition of Notch, thereby restoring Notch responsiveness in ligand-expressing cells (zolkiewska2008adamproteasesligand pages 8-9, zolkiewska2008adamproteasesligand pages 6-8).
Dll1 protein is predominantly localized at the plasma membrane or cell surface, where it functions as a contact-dependent signaling ligand (geffers2007divergentfunctionsand pages 6-8, geffers2008biochemicalnonequivalenceof pages 59-62, geffers2007divergentfunctionsand pages 5-6). Immunofluorescence and surface-biotinylation experiments demonstrate efficient cell-surface presentation in both cultured cells and embryonic tissues (geffers2008biochemicalnonequivalenceof pages 59-62, geffers2007divergentfunctionsand pages 5-6). In presomitic mesoderm cells and wing-disc epithelia, endogenous Dll1 colocalizes with apical membrane markers and outlines cell–cell contacts (geffers2007divergentfunctionsand pages 6-8, geffers2007divergentfunctionsand pages 5-6).
In addition to its primary membrane localization, Dll1 is also present in intracellular vesicular compartments, including the cis-Golgi network (marked by GM130 colocalization) and clathrin-coated vesicles/early endosomes (geffers2007divergentfunctionsand pages 6-8, geffers2007divergentfunctionsand pages 5-6, serth2015ofucosylationofdll3 pages 5-8). This intracellular pool reflects the protein's trafficking through the secretory pathway and its endocytosis following receptor engagement (geffers2007divergentfunctionsand pages 5-6, serth2015ofucosylationofdll3 pages 5-8). The distribution between membrane and intracellular pools can be influenced by coexpression with other Notch-pathway components such as Dll3 (serth2015ofucosylationofdll3 pages 5-8).
Functionally, Dll1's membrane localization is essential for trans-activation: disruption of the DSL domain or intracellular-domain-dependent trafficking impairs surface presentation and abolishes signaling (geffers2008biochemicalnonequivalenceof pages 59-62, geffers2008biochemicalnonequivalenceof pages 90-93, geffers2008biochemicalnonequivalenceof pages 81-84). This contrasts with the divergent ligand Dll3, which is predominantly intracellular and largely absent from the cell surface (geffers2007divergentfunctionsand pages 6-8, geffers2007divergentfunctionsand pages 5-6).
Dll1 participates in multiple developmental and physiological processes through Notch-dependent regulation of cell-fate decisions:
| Tissue/system | Specific Dll1 function | Key evidence | Outcome when Dll1 signaling is disrupted |
|---|---|---|---|
| Somitogenesis and axial skeleton | Provides contact-dependent Notch signaling in the presomitic mesoderm; coordinates segmentation-clock activity, somite epithelialization, boundary maintenance, and rostrocaudal identity. Dll1 RNA and protein exhibit rostrally propagating oscillations coupled to somite formation. | Live imaging detected oscillatory Dll1 protein waves in mouse presomitic mesoderm; genetic studies showed that Dll1 is required for organized somites and appropriate expression of polarity markers. Restricted expression in caudal somite compartments is also important for intervertebral-joint morphogenesis. (geffers2008biochemicalnonequivalenceof pages 26-28, teppner2007compartmentalisedexpressionof pages 11-12, shimojo2016oscillatorycontrolof pages 2-3) | Loss disrupts somite epithelialization and boundaries, deranges rostrocaudal polarity, and disorganizes myotome and sclerotome patterning. Inappropriate spatial expression causes vertebral and intervertebral-joint abnormalities. (geffers2008biochemicalnonequivalenceof pages 26-28, teppner2007compartmentalisedexpressionof pages 11-12) |
| Skeletal muscle | Maintains embryonic myogenic progenitors and regulates the timing of differentiation; oscillatory Dll1 input helps balance muscle-stem-cell self-renewal against differentiation during growth and regeneration. | Delta1-mutant studies associate reduced signaling with premature myogenic differentiation and progenitor depletion. Later mouse work showed that Dll1 dynamics—not merely its mean abundance—are important for muscle stem-cell maintenance. (tveriakhina2018theectodomainsdetermine pages 26-27, serth2015ofucosylationofdll3 pages 20-21) | Disruption causes premature differentiation, loss of the progenitor pool, severe muscle hypotrophy, and impaired regenerative self-renewal. (tveriakhina2018theectodomainsdetermine pages 26-27, serth2015ofucosylationofdll3 pages 20-21) |
| Nervous system | Activates Notch in neighboring neural progenitors to mediate lateral inhibition, restrain premature neurogenesis, and preserve undifferentiated progenitor populations. | Dll1-deficient embryos display neural overproduction and central nervous-system hyperplasia, consistent with failure of Notch-dependent control of neuronal differentiation. (geffers2008biochemicalnonequivalenceof pages 26-28) | Premature or excessive neuronal differentiation depletes progenitors and produces a hyperplastic embryonic central nervous system. (geffers2008biochemicalnonequivalenceof pages 26-28) |
| Immune and hematopoietic systems | Regulates lineage decisions through Notch, including marginal-zone B-cell generation and context-dependent T-lineage induction. Dendritic-cell Dll1 also supports antigen-specific CD8 T-cell effector and memory responses. | Mouse genetics indicate that Dll1 is required for marginal-zone B cells but is not the indispensable physiological thymic ligand for T-cell generation; Dll4 has that dominant role. In tumor models, CD11c-lineage Dll1 deletion reduced CD8 effector-memory differentiation and IFN-γ production, whereas clustered DLL1 restored antitumor responses. (hirano2020deltalike1and pages 4-6, tveriakhina2018theectodomainsdetermine pages 26-27, tchekneva2019determinantrolesof pages 1-2, hirano2020deltalike1and pages 17-17) | Depending on context, loss impairs marginal-zone B-cell formation, weakens antigen-specific CD8 activity and effector-memory differentiation, lowers IFN-γ, increases IL-4 and immunosuppressive cell populations, and accelerates experimental tumor growth. (tveriakhina2018theectodomainsdetermine pages 26-27, tchekneva2019determinantrolesof pages 1-2) |
| Vascular system | Maintains fetal arterial endothelial identity by activating Notch1 and sustaining ephrin-B2, VEGFR2, and neuropilin-1; thereby preserves VEGF responsiveness and coordinated vessel-wall differentiation. | Endothelial Dll1 becomes artery-selective from about embryonic day 13.5. Conditional deletion eliminates later arterial NICD despite continued Notch1 and DLL4 expression; constitutively active Notch rescues arterial markers, placing Dll1 upstream of Notch. (sorensen2009dll1mediatednotchactivation pages 6-7, sorensen2009dll1mediatednotchactivation pages 3-4, sorensen2009dll1mediatednotchactivation pages 4-5, sorensen2009dll1mediatednotchactivation pages 1-2) | Loss causes reduced arterial-marker expression, ectopic venous COUP-TFII, reduced arterial lumen size, altered capillary branching, impaired VEGF responsiveness, and defective arterial endothelial identity. (sorensen2009dll1mediatednotchactivation pages 4-5, sorensen2009dll1mediatednotchactivation pages 5-6, sorensen2009dll1mediatednotchactivation pages 2-3) |
Table: This table summarizes experimentally supported functions of mouse Dll1 across major tissues and links each function to the phenotypes caused by disrupted Dll1 signaling.
Dll1 is a central component of the vertebrate segmentation clock, which generates periodic somites along the embryonic anterior–posterior axis (shimojo2016oscillatorycontrolof pages 2-3, bone2012investigatingtheregulation pages 170-175). Dll1 mRNA and protein expression oscillate dynamically in the presomitic mesoderm (PSM) with a period matching somite formation (approximately 2 hours in mouse) (shimojo2016oscillatorycontrolof pages 2-3, bone2012investigatingtheregulation pages 114-122). Live imaging revealed that Dll1 protein waves propagate rostrally through the PSM and regress caudally as each new somite forms (shimojo2016oscillatorycontrolof pages 2-3). These oscillations are part of a negative-feedback network involving Hes7, which represses Dll1 transcription, and Lunatic fringe (Lfng), which modulates Notch–Dll1 interaction kinetics (bone2012investigatingtheregulation pages 170-175, bone2012investigatingtheregulation pages 46-51). Nascent Dll1 transcription cycles in phase with Wnt targets such as Snail1 but out of phase with canonical Notch targets (bone2012investigatingtheregulation pages 114-122).
Functionally, Dll1-mediated Notch signaling is required for somite epithelialization, boundary maintenance, and rostrocaudal polarity (geffers2008biochemicalnonequivalenceof pages 26-28, teppner2007compartmentalisedexpressionof pages 11-12). Loss of Dll1 disrupts somite organization, impairs myotome and sclerotome patterning, and deranges polarity markers such as Uncx4.1 and Tbx18 (geffers2008biochemicalnonequivalenceof pages 26-28). Compartmentalized Dll1 expression in caudal somite halves is also necessary for proper intervertebral-joint formation (teppner2007compartmentalisedexpressionof pages 11-12).
Dll1 maintains embryonic myogenic progenitor populations and regulates the timing of differentiation (tveriakhina2018theectodomainsdetermine pages 26-27, serth2015ofucosylationofdll3 pages 20-21). Delta1-deficient embryos exhibit premature myogenic differentiation, depletion of muscle progenitors, and severe muscle hypotrophy (tveriakhina2018theectodomainsdetermine pages 26-27, serth2015ofucosylationofdll3 pages 20-21). More recent work (2021–2025) demonstrated that oscillatory Dll1 expression—rather than simply its steady-state level—is critical for balancing self-renewal and differentiation of muscle stem cells during postnatal growth and regeneration (peng2025stagespecificandcellautonomous pages 1-2). Stage-specific deletion studies revealed both neighboring-cell and cell-autonomous Dll1 functions in myogenic regulation (peng2025stagespecificandcellautonomous pages 1-2).
In the developing nervous system, Dll1 activates Notch to mediate lateral inhibition, thereby restraining premature neurogenesis and maintaining neural progenitor pools (geffers2008biochemicalnonequivalenceof pages 26-28). Dll1-deficient embryos develop a hyperplastic central nervous system due to excessive neuronal differentiation (geffers2008biochemicalnonequivalenceof pages 26-28). This lateral-inhibition mechanism ensures coordinated neuronal production and proper nervous-system patterning.
Dll1 plays context-dependent roles in lymphoid development. Genetic studies indicate that Dll1 is specifically required for marginal-zone B-cell generation but is not the indispensable thymic ligand for T-cell production; Dll4 fulfills that essential role (tveriakhina2018theectodomainsdetermine pages 26-27, hirano2020deltalike1and pages 17-17). Nevertheless, Dll1 can support T-lineage differentiation when appropriately expressed: ectopic Dll1 in stromal cells induces T-cell development from hematopoietic progenitors in vitro, and Dll1-bearing cells promoted differentiation of CD19− Thy1+ CD25+ T-lineage cells from fetal liver progenitors (hirano2020deltalike1and pages 4-6, hirano2020deltalike1and pages 17-18).
In mature immune function, dendritic-cell-expressed Dll1 regulates T-cell effector and memory responses (tchekneva2019determinantrolesof pages 1-2). CD11c-lineage-specific deletion of Dll1 impaired antigen-specific CD8+ T-cell activity, reduced effector-memory differentiation, decreased IFN-γ production, increased IL-4 and immunosuppressive regulatory T cells, and accelerated tumor growth in experimental models (tchekneva2019determinantrolesof pages 1-2). Multivalent clustered DLL1 restored anti-tumor T-cell responses, whereas monomeric soluble DLL1 suppressed tumor and allograft rejection (tchekneva2019determinantrolesof pages 1-2). These findings position Dll1 as an important regulator of adaptive immunity and anti-tumor immune responses.
Dll1 is essential for maintaining fetal arterial endothelial identity (sorensen2009dll1mediatednotchactivation pages 7-8, sorensen2009dll1mediatednotchactivation pages 6-7, sorensen2009dll1mediatednotchactivation pages 4-5). Dll1 expression is selectively upregulated in arterial endothelial cells beginning around embryonic day 13.5 and is required for sustained Notch1 activation in fetal arteries (sorensen2009dll1mediatednotchactivation pages 6-7, sorensen2009dll1mediatednotchactivation pages 3-4). Endothelial-specific deletion of Dll1 eliminates detectable NICD and downstream Notch signaling in arterial endothelium despite continued expression of Notch1 and other ligands such as Dll4, demonstrating Dll1's nonredundant function in this context (sorensen2009dll1mediatednotchactivation pages 6-7, sorensen2009dll1mediatednotchactivation pages 4-5).
Loss of Dll1-mediated Notch signaling causes loss of arterial markers (ephrinB2, VEGFR2, neuropilin-1) and ectopic expression of the venous marker COUP-TFII (sorensen2009dll1mediatednotchactivation pages 4-5, sorensen2009dll1mediatednotchactivation pages 5-6). Dll1/Notch activity also directly promotes neuropilin-1 (Nrp1) transcription through RBPjκ sites in the Nrp1 promoter, thereby preserving VEGFR2/NRP1-mediated VEGF responsiveness (sorensen2009dll1mediatednotchactivation pages 1-2, sorensen2009dll1mediatednotchactivation pages 5-6, sorensen2009dll1mediatednotchactivation pages 2-3). Dll1 mutants exhibit reduced arterial lumen size, altered capillary branching, and impaired vascular structure (sorensen2009dll1mediatednotchactivation pages 4-5, sorensen2009dll1mediatednotchactivation pages 5-6), although gross arteriovenous shunts are not observed (sorensen2009dll1mediatednotchactivation pages 5-6). These findings establish Dll1 as a critical regulator of arterial endothelial differentiation, VEGF signaling competence, and coordinated vessel-wall development.
Recent studies continue to expand understanding of Dll1 function:
A 2025 Nature Communications study demonstrated stage-specific and cell-autonomous functions of Dll1 in skeletal muscle stem cells and myogenesis (peng2025stagespecificandcellautonomous pages 1-2). Dll1 conditional knockout in muscle stem cells disrupts homeostasis in adult mice and impairs regeneration, effects that are intrinsic and cannot be rescued by coculture with wild-type cells. The study also identified a cell-autonomous role for a Dll1-derived intracellular domain in promoting myoblast differentiation and fusion (peng2025stagespecificandcellautonomous pages 1-2).
Research published in 2026 in the Journal of Atherosclerosis and Thrombosis examined the role of Dll1 blockade in atherosclerotic lesion formation (Orkhonselenge et al., 2026). Because genetic deletion of Dll1 is embryonic lethal, the investigators used Dll1-blocking antibodies in mouse atherosclerosis models. Dll1 inhibition reduced lesion formation and attenuated plaque vulnerability, suggesting Dll1 contributes to atherosclerotic pathogenesis and may represent a therapeutic target for cardiovascular disease.
Recent structural and functional studies have continued to elucidate how Dll1 differs from closely related ligands such as Dll4. Work published in 2023 (Nature Chemical Biology) developed affinity-matured Dll4 variants as broad-spectrum Notch modulators, providing tools to dissect ligand-specific versus receptor-specific contributions to signaling. Comparative domain-swap and mutagenesis studies published through 2024 reinforced that the Dll1 extracellular domain—particularly the MNNL/C2, DSL, and proximal EGF repeats—determines ligand-selective receptor activation and developmental outcomes (hirano2020deltalike1and pages 1-2, tveriakhina2018theectodomainsdetermine pages 1-2).
Although Dll1 itself has not been the primary target of recent clinical trials, investigations into Notch ligand biology and Delta-family proteins continue. Studies on Dll3-targeted therapies in neuroendocrine cancers have highlighted general principles of DSL ligand function and provided comparative context for Dll1 research. Additionally, a 2026 study examined DLL-1 as a biomarker for sepsis prediction in emergency-department patients (Hübner et al., 2026), demonstrating elevated serum Dll1 concentrations in sepsis patients and suggesting that Dll1 may reflect disease severity and immune/endothelial activation.
Dll1 is now recognized as a canonical, indispensable Notch ligand with context-dependent, nonredundant functions across multiple developmental and physiological systems. Expert consensus, based on extensive genetic, biochemical, and cell-biological evidence, establishes several key principles:
Mechanistic Model: Dll1-mediated Notch activation requires membrane anchorage, ligand endocytosis to generate mechanical force, sequential ADAM and γ-secretase proteolysis of Notch, and nuclear translocation of NICD for transcriptional regulation (hirano2020deltalike1and pages 1-2, tveriakhina2018theectodomainsdetermine pages 1-2, geffers2008biochemicalnonequivalenceof pages 14-17, wang2011notchsignalingand pages 3-5).
Ligand Specificity: Dll1 and Dll4 are structurally similar but functionally distinct. Dll1 activates Notch1 and Notch2 approximately equally, whereas Dll4 preferentially activates Notch1. These differences map primarily to the extracellular C2/MNNL, DSL, and proximal EGF regions (tveriakhina2018theectodomainsdetermine pages 1-2, tveriakhina2018theectodomainsdetermine pages 2-5).
Developmental Essentiality: Complete loss of Dll1 causes embryonic lethality due to severe defects in somitogenesis, neurogenesis, vascular development, and other processes (geffers2008biochemicalnonequivalenceof pages 26-28). Tissue-specific deletions reveal stage- and context-dependent requirements (peng2025stagespecificandcellautonomous pages 1-2, sorensen2009dll1mediatednotchactivation pages 4-5).
Dynamic Regulation: Dll1 expression is not static; oscillatory dynamics in the presomitic mesoderm and muscle stem cells are functionally important and cannot be replaced by steady-state expression (shimojo2016oscillatorycontrolof pages 2-3, bone2012investigatingtheregulation pages 114-122, peng2025stagespecificandcellautonomous pages 1-2).
Proteolytic Regulation: ADAM-mediated Dll1 shedding modulates signaling by producing inactive soluble fragments and relieving cis-inhibition (dyczynska2007proteolyticprocessingof pages 7-8, dyczynska2007proteolyticprocessingof pages 1-2, zolkiewska2008adamproteasesligand pages 8-9).
Delta-like protein 1 (Dll1; UniProt Q61483) is a type I transmembrane Notch ligand in mouse, characterized by an N-terminal C2/MNNL domain, a DSL domain, eight EGF-like repeats including a DOS motif, and a short intracellular tail. Dll1 activates Notch receptors on neighboring cells through a multi-step process involving receptor binding, endocytosis-dependent mechanical force generation, sequential proteolytic cleavage, and nuclear translocation of the Notch intracellular domain. The protein is predominantly localized at the plasma membrane, with secondary trafficking through Golgi and endosomal compartments. Dll1 undergoes proteolytic processing by ADAM metalloproteases and γ-secretase, producing soluble, membrane-associated, and intracellular forms.
Biologically, Dll1 is essential for somitogenesis and the segmentation clock, skeletal muscle development and stem-cell maintenance, neurogenesis, immune-cell differentiation (particularly marginal-zone B cells and T-cell effector responses), and fetal arterial endothelial specification. Recent research (2023–2026) continues to expand understanding of Dll1 in muscle regeneration, atherosclerosis, and comparative ligand biology. Dll1 functions through context-dependent Notch signaling to regulate cell-fate decisions, maintain progenitor pools, and coordinate developmental patterning across multiple organ systems.
References
(tveriakhina2018theectodomainsdetermine pages 2-5): Lena Tveriakhina, Karin Schuster-Gossler, Sanchez M Jarrett, Marie B Andrawes, Meike Rohrbach, Stephen C Blacklow, and Achim Gossler. The ectodomains determine ligand function in vivo and selectivity of dll1 and dll4 toward notch1 and notch2 in vitro. eLife, Oct 2018. URL: https://doi.org/10.7554/elife.40045, doi:10.7554/elife.40045. This article has 53 citations and is from a domain leading peer-reviewed journal.
(wang2011notchsignalingand pages 3-5): Michael M. Wang. Notch signaling and notch signaling modifiers. The international journal of biochemistry & cell biology, 43 11:1550-62, Nov 2011. URL: https://doi.org/10.1016/j.biocel.2011.08.005, doi:10.1016/j.biocel.2011.08.005. This article has 183 citations.
(ladi2005thedivergentdsl pages 6-7): Ena Ladi, James T. Nichols, Weihong Ge, Alison Miyamoto, Christine Yao, Liang-Tung Yang, Jim Boulter, Yi E. Sun, Chris Kintner, and Gerry Weinmaster. The divergent dsl ligand dll3 does not activate notch signaling but cell autonomously attenuates signaling induced by other dsl ligands. The Journal of Cell Biology, 170:983-992, Sep 2005. URL: https://doi.org/10.1083/jcb.200503113, doi:10.1083/jcb.200503113. This article has 404 citations.
(tveriakhina2018theectodomainsdetermine pages 1-2): Lena Tveriakhina, Karin Schuster-Gossler, Sanchez M Jarrett, Marie B Andrawes, Meike Rohrbach, Stephen C Blacklow, and Achim Gossler. The ectodomains determine ligand function in vivo and selectivity of dll1 and dll4 toward notch1 and notch2 in vitro. eLife, Oct 2018. URL: https://doi.org/10.7554/elife.40045, doi:10.7554/elife.40045. This article has 53 citations and is from a domain leading peer-reviewed journal.
(geffers2007divergentfunctionsand pages 6-8): Insa Geffers, Katrin Serth, Gavin Chapman, Robert Jaekel, Karin Schuster-Gossler, Ralf Cordes, Duncan B. Sparrow, Elisabeth Kremmer, Sally L. Dunwoodie, Thomas Klein, and Achim Gossler. Divergent functions and distinct localization of the notch ligands dll1 and dll3 in vivo. The Journal of Cell Biology, 178:465-476, Jul 2007. URL: https://doi.org/10.1083/jcb.200702009, doi:10.1083/jcb.200702009. This article has 246 citations.
(handford2018structuralinsightsinto pages 6-9): Penny A. Handford, Boguslawa Korona, Richard Suckling, Christina Redfield, and Susan M. Lea. Structural insights into notch receptor-ligand interactions. Advances in experimental medicine and biology, 1066:33-46, Jan 2018. URL: https://doi.org/10.1007/978-3-319-89512-3_2, doi:10.1007/978-3-319-89512-3_2. This article has 25 citations and is from a peer-reviewed journal.
(handford2018structuralinsightsinto pages 21-23): Penny A. Handford, Boguslawa Korona, Richard Suckling, Christina Redfield, and Susan M. Lea. Structural insights into notch receptor-ligand interactions. Advances in experimental medicine and biology, 1066:33-46, Jan 2018. URL: https://doi.org/10.1007/978-3-319-89512-3_2, doi:10.1007/978-3-319-89512-3_2. This article has 25 citations and is from a peer-reviewed journal.
(geffers2008biochemicalnonequivalenceof pages 87-90): Insa Geffers. Biochemical non-equivalence of the dsl proteins dll1 and dll3. ArXiv, Jan 2008. URL: https://doi.org/10.15488/7044, doi:10.15488/7044. This article has 0 citations.
(cordle2008aconservedface pages 17-21): Jemima Cordle, Steven Johnson, Joyce Zi Yan Tay, Pietro Roversi, Marian B Wilkin, Beatriz Hernández de Madrid, Hideyuki Shimizu, Sacha Jensen, Pat Whiteman, Boquan Jin, Christina Redfield, Martin Baron, Susan M Lea, and Penny A Handford. A conserved face of the jagged/serrate dsl domain is involved in notch trans-activation and cis-inhibition. Nature Structural &Molecular Biology, 15:849-857, Jul 2008. URL: https://doi.org/10.1038/nsmb.1457, doi:10.1038/nsmb.1457. This article has 355 citations.
(hirano2020deltalike1and pages 8-9): Ken-ichi Hirano, Akiko Suganami, Yutaka Tamura, Hideo Yagita, Sonoko Habu, Motoo Kitagawa, Takehito Sato, and Katsuto Hozumi. Delta-like 1 and delta-like 4 differently require their extracellular domains for triggering notch signaling in mice. Jan 2020. URL: https://doi.org/10.7554/elife.50979, doi:10.7554/elife.50979. This article has 19 citations and is from a domain leading peer-reviewed journal.
(geffers2007divergentfunctionsand pages 4-5): Insa Geffers, Katrin Serth, Gavin Chapman, Robert Jaekel, Karin Schuster-Gossler, Ralf Cordes, Duncan B. Sparrow, Elisabeth Kremmer, Sally L. Dunwoodie, Thomas Klein, and Achim Gossler. Divergent functions and distinct localization of the notch ligands dll1 and dll3 in vivo. The Journal of Cell Biology, 178:465-476, Jul 2007. URL: https://doi.org/10.1083/jcb.200702009, doi:10.1083/jcb.200702009. This article has 246 citations.
(hirano2020deltalike1and pages 4-6): Ken-ichi Hirano, Akiko Suganami, Yutaka Tamura, Hideo Yagita, Sonoko Habu, Motoo Kitagawa, Takehito Sato, and Katsuto Hozumi. Delta-like 1 and delta-like 4 differently require their extracellular domains for triggering notch signaling in mice. Jan 2020. URL: https://doi.org/10.7554/elife.50979, doi:10.7554/elife.50979. This article has 19 citations and is from a domain leading peer-reviewed journal.
(dyczynska2007proteolyticprocessingof pages 7-8): Emilia Dyczynska, Danqiong Sun, Haiqing Yi, Atsuko Sehara-Fujisawa, Carl P. Blobel, and Anna Zolkiewska. Proteolytic processing of delta-like 1 by adam proteases*. Journal of Biological Chemistry, 282:436-444, Jan 2007. URL: https://doi.org/10.1074/jbc.m605451200, doi:10.1074/jbc.m605451200. This article has 181 citations and is from a domain leading peer-reviewed journal.
(zolkiewska2008adamproteasesligand pages 4-6): A. Zolkiewska. Adam proteases: ligand processing and modulation of the notch pathway. Cellular and Molecular Life Sciences, 65:2056-2068, Mar 2008. URL: https://doi.org/10.1007/s00018-008-7586-4, doi:10.1007/s00018-008-7586-4. This article has 138 citations and is from a domain leading peer-reviewed journal.
(zolkiewska2008adamproteasesligand pages 8-9): A. Zolkiewska. Adam proteases: ligand processing and modulation of the notch pathway. Cellular and Molecular Life Sciences, 65:2056-2068, Mar 2008. URL: https://doi.org/10.1007/s00018-008-7586-4, doi:10.1007/s00018-008-7586-4. This article has 138 citations and is from a domain leading peer-reviewed journal.
(zolkiewska2008adamproteasesligand pages 2-4): A. Zolkiewska. Adam proteases: ligand processing and modulation of the notch pathway. Cellular and Molecular Life Sciences, 65:2056-2068, Mar 2008. URL: https://doi.org/10.1007/s00018-008-7586-4, doi:10.1007/s00018-008-7586-4. This article has 138 citations and is from a domain leading peer-reviewed journal.
(geffers2008biochemicalnonequivalenceof pages 90-93): Insa Geffers. Biochemical non-equivalence of the dsl proteins dll1 and dll3. ArXiv, Jan 2008. URL: https://doi.org/10.15488/7044, doi:10.15488/7044. This article has 0 citations.
(dyczynska2007proteolyticprocessingof pages 4-5): Emilia Dyczynska, Danqiong Sun, Haiqing Yi, Atsuko Sehara-Fujisawa, Carl P. Blobel, and Anna Zolkiewska. Proteolytic processing of delta-like 1 by adam proteases*. Journal of Biological Chemistry, 282:436-444, Jan 2007. URL: https://doi.org/10.1074/jbc.m605451200, doi:10.1074/jbc.m605451200. This article has 181 citations and is from a domain leading peer-reviewed journal.
(dyczynska2007proteolyticprocessingof pages 3-4): Emilia Dyczynska, Danqiong Sun, Haiqing Yi, Atsuko Sehara-Fujisawa, Carl P. Blobel, and Anna Zolkiewska. Proteolytic processing of delta-like 1 by adam proteases*. Journal of Biological Chemistry, 282:436-444, Jan 2007. URL: https://doi.org/10.1074/jbc.m605451200, doi:10.1074/jbc.m605451200. This article has 181 citations and is from a domain leading peer-reviewed journal.
(hirano2020deltalike1and pages 1-2): Ken-ichi Hirano, Akiko Suganami, Yutaka Tamura, Hideo Yagita, Sonoko Habu, Motoo Kitagawa, Takehito Sato, and Katsuto Hozumi. Delta-like 1 and delta-like 4 differently require their extracellular domains for triggering notch signaling in mice. Jan 2020. URL: https://doi.org/10.7554/elife.50979, doi:10.7554/elife.50979. This article has 19 citations and is from a domain leading peer-reviewed journal.
(geffers2008biochemicalnonequivalenceof pages 14-17): Insa Geffers. Biochemical non-equivalence of the dsl proteins dll1 and dll3. ArXiv, Jan 2008. URL: https://doi.org/10.15488/7044, doi:10.15488/7044. This article has 0 citations.
(vazquezulloa2022reversibleandbidirectional pages 7-8): Elenaé Vázquez-Ulloa, Kai-Lan Lin, Marcela Lizano, and Cecilia Sahlgren. Reversible and bidirectional signaling of notch ligands. Critical Reviews in Biochemistry and Molecular Biology, 57:377-398, Jul 2022. URL: https://doi.org/10.1080/10409238.2022.2113029, doi:10.1080/10409238.2022.2113029. This article has 29 citations and is from a peer-reviewed journal.
(zolkiewska2008adamproteasesligand pages 6-8): A. Zolkiewska. Adam proteases: ligand processing and modulation of the notch pathway. Cellular and Molecular Life Sciences, 65:2056-2068, Mar 2008. URL: https://doi.org/10.1007/s00018-008-7586-4, doi:10.1007/s00018-008-7586-4. This article has 138 citations and is from a domain leading peer-reviewed journal.
(vazquezulloa2022reversibleandbidirectional pages 5-7): Elenaé Vázquez-Ulloa, Kai-Lan Lin, Marcela Lizano, and Cecilia Sahlgren. Reversible and bidirectional signaling of notch ligands. Critical Reviews in Biochemistry and Molecular Biology, 57:377-398, Jul 2022. URL: https://doi.org/10.1080/10409238.2022.2113029, doi:10.1080/10409238.2022.2113029. This article has 29 citations and is from a peer-reviewed journal.
(geffers2008biochemicalnonequivalenceof pages 75-78): Insa Geffers. Biochemical non-equivalence of the dsl proteins dll1 and dll3. ArXiv, Jan 2008. URL: https://doi.org/10.15488/7044, doi:10.15488/7044. This article has 0 citations.
(dyczynska2007proteolyticprocessingof pages 1-2): Emilia Dyczynska, Danqiong Sun, Haiqing Yi, Atsuko Sehara-Fujisawa, Carl P. Blobel, and Anna Zolkiewska. Proteolytic processing of delta-like 1 by adam proteases*. Journal of Biological Chemistry, 282:436-444, Jan 2007. URL: https://doi.org/10.1074/jbc.m605451200, doi:10.1074/jbc.m605451200. This article has 181 citations and is from a domain leading peer-reviewed journal.
(klose2015solublenotchligand pages 5-7): Ralph Klose, Caroline Berger, Iris Moll, M. Gordian Adam, Frank Schwarz, Kerstin Mohr, Hellmut G. Augustin, and Andreas Fischer. Soluble notch ligand and receptor peptides act antagonistically during angiogenesis. Cardiovascular research, 107 1:153-63, Jul 2015. URL: https://doi.org/10.1093/cvr/cvv151, doi:10.1093/cvr/cvv151. This article has 45 citations and is from a domain leading peer-reviewed journal.
(geffers2008biochemicalnonequivalenceof pages 59-62): Insa Geffers. Biochemical non-equivalence of the dsl proteins dll1 and dll3. ArXiv, Jan 2008. URL: https://doi.org/10.15488/7044, doi:10.15488/7044. This article has 0 citations.
(geffers2007divergentfunctionsand pages 5-6): Insa Geffers, Katrin Serth, Gavin Chapman, Robert Jaekel, Karin Schuster-Gossler, Ralf Cordes, Duncan B. Sparrow, Elisabeth Kremmer, Sally L. Dunwoodie, Thomas Klein, and Achim Gossler. Divergent functions and distinct localization of the notch ligands dll1 and dll3 in vivo. The Journal of Cell Biology, 178:465-476, Jul 2007. URL: https://doi.org/10.1083/jcb.200702009, doi:10.1083/jcb.200702009. This article has 246 citations.
(serth2015ofucosylationofdll3 pages 5-8): Katrin Serth, Karin Schuster-Gossler, Elisabeth Kremmer, Birte Hansen, Britta Marohn-Köhn, and Achim Gossler. O-fucosylation of dll3 is required for its function during somitogenesis. PLoS ONE, 10:e0123776, Apr 2015. URL: https://doi.org/10.1371/journal.pone.0123776, doi:10.1371/journal.pone.0123776. This article has 72 citations and is from a peer-reviewed journal.
(geffers2008biochemicalnonequivalenceof pages 81-84): Insa Geffers. Biochemical non-equivalence of the dsl proteins dll1 and dll3. ArXiv, Jan 2008. URL: https://doi.org/10.15488/7044, doi:10.15488/7044. This article has 0 citations.
(geffers2008biochemicalnonequivalenceof pages 26-28): Insa Geffers. Biochemical non-equivalence of the dsl proteins dll1 and dll3. ArXiv, Jan 2008. URL: https://doi.org/10.15488/7044, doi:10.15488/7044. This article has 0 citations.
(teppner2007compartmentalisedexpressionof pages 11-12): Ingeborg Teppner, Sonja Becker, Martin Hrabé de Angelis, Achim Gossler, and Johannes Beckers. Compartmentalised expression of delta-like 1 in epithelial somites is required for the formation of intervertebral joints. BMC Developmental Biology, 7:68-68, Jun 2007. URL: https://doi.org/10.1186/1471-213x-7-68, doi:10.1186/1471-213x-7-68. This article has 12 citations and is from a peer-reviewed journal.
(shimojo2016oscillatorycontrolof pages 2-3): Hiromi Shimojo, Akihiro Isomura, Toshiyuki Ohtsuka, Hiroshi Kori, Hitoshi Miyachi, and Ryoichiro Kageyama. Oscillatory control of delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis. Genes & Development, 30:102-116, Jan 2016. URL: https://doi.org/10.1101/gad.270785.115, doi:10.1101/gad.270785.115. This article has 172 citations and is from a highest quality peer-reviewed journal.
(tveriakhina2018theectodomainsdetermine pages 26-27): Lena Tveriakhina, Karin Schuster-Gossler, Sanchez M Jarrett, Marie B Andrawes, Meike Rohrbach, Stephen C Blacklow, and Achim Gossler. The ectodomains determine ligand function in vivo and selectivity of dll1 and dll4 toward notch1 and notch2 in vitro. eLife, Oct 2018. URL: https://doi.org/10.7554/elife.40045, doi:10.7554/elife.40045. This article has 53 citations and is from a domain leading peer-reviewed journal.
(serth2015ofucosylationofdll3 pages 20-21): Katrin Serth, Karin Schuster-Gossler, Elisabeth Kremmer, Birte Hansen, Britta Marohn-Köhn, and Achim Gossler. O-fucosylation of dll3 is required for its function during somitogenesis. PLoS ONE, 10:e0123776, Apr 2015. URL: https://doi.org/10.1371/journal.pone.0123776, doi:10.1371/journal.pone.0123776. This article has 72 citations and is from a peer-reviewed journal.
(tchekneva2019determinantrolesof pages 1-2): Elena E. Tchekneva, Mounika U.L. Goruganthu, Roman V. Uzhachenko, Portia L. Thomas, Anneliese Antonucci, Irina Chekneva, Michael Koenig, Longzhu Piao, Anwari Akhter, Maria Teresa P. de Aquino, Parvathi Ranganathan, Nicholas Long, Thomas Magliery, Anna Valujskikh, Jason V. Evans, Rajeswara R. Arasada, Pierre P. Massion, David P. Carbone, Anil Shanker, and Mikhail M. Dikov. Determinant roles of dendritic cell-expressed notch delta-like and jagged ligands on anti-tumor t cell immunity. Journal for Immunotherapy of Cancer, Apr 2019. URL: https://doi.org/10.1186/s40425-019-0566-4, doi:10.1186/s40425-019-0566-4. This article has 65 citations and is from a domain leading peer-reviewed journal.
(hirano2020deltalike1and pages 17-17): Ken-ichi Hirano, Akiko Suganami, Yutaka Tamura, Hideo Yagita, Sonoko Habu, Motoo Kitagawa, Takehito Sato, and Katsuto Hozumi. Delta-like 1 and delta-like 4 differently require their extracellular domains for triggering notch signaling in mice. Jan 2020. URL: https://doi.org/10.7554/elife.50979, doi:10.7554/elife.50979. This article has 19 citations and is from a domain leading peer-reviewed journal.
(sorensen2009dll1mediatednotchactivation pages 6-7): Inga Sörensen, Ralf H. Adams, and Achim Gossler. Dll1-mediated notch activation regulates endothelial identity in mouse fetal arteries. Blood, 113 22:5680-8, May 2009. URL: https://doi.org/10.1182/blood-2008-08-174508, doi:10.1182/blood-2008-08-174508. This article has 560 citations and is from a highest quality peer-reviewed journal.
(sorensen2009dll1mediatednotchactivation pages 3-4): Inga Sörensen, Ralf H. Adams, and Achim Gossler. Dll1-mediated notch activation regulates endothelial identity in mouse fetal arteries. Blood, 113 22:5680-8, May 2009. URL: https://doi.org/10.1182/blood-2008-08-174508, doi:10.1182/blood-2008-08-174508. This article has 560 citations and is from a highest quality peer-reviewed journal.
(sorensen2009dll1mediatednotchactivation pages 4-5): Inga Sörensen, Ralf H. Adams, and Achim Gossler. Dll1-mediated notch activation regulates endothelial identity in mouse fetal arteries. Blood, 113 22:5680-8, May 2009. URL: https://doi.org/10.1182/blood-2008-08-174508, doi:10.1182/blood-2008-08-174508. This article has 560 citations and is from a highest quality peer-reviewed journal.
(sorensen2009dll1mediatednotchactivation pages 1-2): Inga Sörensen, Ralf H. Adams, and Achim Gossler. Dll1-mediated notch activation regulates endothelial identity in mouse fetal arteries. Blood, 113 22:5680-8, May 2009. URL: https://doi.org/10.1182/blood-2008-08-174508, doi:10.1182/blood-2008-08-174508. This article has 560 citations and is from a highest quality peer-reviewed journal.
(sorensen2009dll1mediatednotchactivation pages 5-6): Inga Sörensen, Ralf H. Adams, and Achim Gossler. Dll1-mediated notch activation regulates endothelial identity in mouse fetal arteries. Blood, 113 22:5680-8, May 2009. URL: https://doi.org/10.1182/blood-2008-08-174508, doi:10.1182/blood-2008-08-174508. This article has 560 citations and is from a highest quality peer-reviewed journal.
(sorensen2009dll1mediatednotchactivation pages 2-3): Inga Sörensen, Ralf H. Adams, and Achim Gossler. Dll1-mediated notch activation regulates endothelial identity in mouse fetal arteries. Blood, 113 22:5680-8, May 2009. URL: https://doi.org/10.1182/blood-2008-08-174508, doi:10.1182/blood-2008-08-174508. This article has 560 citations and is from a highest quality peer-reviewed journal.
(bone2012investigatingtheregulation pages 170-175): R Bone. Investigating the regulation of the notch pathway ligand delta-like 1 in the vertebrate segmentation clock. Unknown journal, 2012.
(bone2012investigatingtheregulation pages 114-122): R Bone. Investigating the regulation of the notch pathway ligand delta-like 1 in the vertebrate segmentation clock. Unknown journal, 2012.
(bone2012investigatingtheregulation pages 46-51): R Bone. Investigating the regulation of the notch pathway ligand delta-like 1 in the vertebrate segmentation clock. Unknown journal, 2012.
(peng2025stagespecificandcellautonomous pages 1-2): Ying Peng, Sara Scinto, Beatriz Castro, Haowei Xu, Kashyap Akkinapally, Stephanie N. Oprescu, Feng Yue, Jingjuan Chen, and Shihuan Kuang. Stage-specific and cell-autonomous functions of delta-like 1 in skeletal muscle stem cells and myogenesis. Nature Communications, Sep 2025. URL: https://doi.org/10.1038/s41467-025-63631-8, doi:10.1038/s41467-025-63631-8. This article has 7 citations and is from a highest quality peer-reviewed journal.
(hirano2020deltalike1and pages 17-18): Ken-ichi Hirano, Akiko Suganami, Yutaka Tamura, Hideo Yagita, Sonoko Habu, Motoo Kitagawa, Takehito Sato, and Katsuto Hozumi. Delta-like 1 and delta-like 4 differently require their extracellular domains for triggering notch signaling in mice. Jan 2020. URL: https://doi.org/10.7554/elife.50979, doi:10.7554/elife.50979. This article has 19 citations and is from a domain leading peer-reviewed journal.
(sorensen2009dll1mediatednotchactivation pages 7-8): Inga Sörensen, Ralf H. Adams, and Achim Gossler. Dll1-mediated notch activation regulates endothelial identity in mouse fetal arteries. Blood, 113 22:5680-8, May 2009. URL: https://doi.org/10.1182/blood-2008-08-174508, doi:10.1182/blood-2008-08-174508. This article has 560 citations and is from a highest quality peer-reviewed journal.