Gene Symbol: Dll1
Description: delta like canonical Notch ligand 1
Alias: delta-like protein 1, delta1, drosophila Delta homolog 1
Species: rat
Products:     Dll1

Top Publications

  1. Fiuza U, Arias A. Cell and molecular biology of Notch. J Endocrinol. 2007;194:459-74 pubmed
    ..In this review, we will describe the multiple roles of Notch and how various factors can regulate Notch signalling...
  2. Gray G, Mann R, Mitsiadis E, Henrique D, Carcangiu M, Banks A, et al. Human ligands of the Notch receptor. Am J Pathol. 1999;154:785-94 pubmed
    ..three human homologues of the Notch ligands Delta and Serrate, human Jagged1 (HJ1), human Jagged2 (HJ2), and human Delta1 (H-Delta-1), and determined their chromosomal localizations...
  3. Irvin D, Nakano I, Paucar A, Kornblum H. Patterns of Jagged1, Jagged2, Delta-like 1 and Delta-like 3 expression during late embryonic and postnatal brain development suggest multiple functional roles in progenitors and differentiated cells. J Neurosci Res. 2004;75:330-43 pubmed
    ..Taken together, these results support multiple and differing roles for the various ligands during and after central nervous system (CNS) development. ..
  4. Brooker R, Hozumi K, Lewis J. Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear. Development. 2006;133:1277-86 pubmed
    ..We have used a Cre-LoxP approach to knock out two of these ligands, Delta1 (Dll1) and Jagged1 (Jag1), in the mouse ear...
  5. Cordes R, Schuster Gossler K, Serth K, Gossler A. Specification of vertebral identity is coupled to Notch signalling and the segmentation clock. Development. 2004;131:1221-33 pubmed
    ..mesoderm, we generated transgenic mice that express in the paraxial mesoderm a dominant-negative version of Delta1. Transgenic mice with reduced Notch activity in the presomitic mesoderm as indicated by loss of Hes5 expression ..
  6. Kobayashi T, Terada Y, Kuwana H, Tanaka H, Okado T, Kuwahara M, et al. Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury. Kidney Int. 2008;73:1240-50 pubmed publisher
    ..Recombinant Delta-1 significantly stimulated NRK-52E cell proliferation. Our study suggests that the Delta-1/Notch-2/Hes-1 signaling pathway may regulate the regeneration and proliferation of renal tubules during acute kidney injury. ..
  7. Kawaguchi D, Yoshimatsu T, Hozumi K, Gotoh Y. Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon. Development. 2008;135:3849-58 pubmed publisher
    ..We found that the expression patterns of the Notch ligand delta-like 1 (Dll1) and of the active form of Notch1 were mutually exclusive and segregated into distinct NPC subpopulations in the ..
  8. Pellegrinet L, Rodilla V, Liu Z, Chen S, Koch U, Espinosa L, et al. Dll1- and dll4-mediated notch signaling are required for homeostasis of intestinal stem cells. Gastroenterology. 2011;140:1230-1240.e1-7 pubmed publisher
    ..Furthermore, we investigated whether the induction of goblet cell differentiation that results from loss of Notch requires the transcription factor Krüppel-like factor 4 (Klf4)...
  9. Mizuhara E, Nakatani T, Minaki Y, Sakamoto Y, Ono Y, Takai Y. MAGI1 recruits Dll1 to cadherin-based adherens junctions and stabilizes it on the cell surface. J Biol Chem. 2005;280:26499-507 pubmed
    ..In the present study, we found that, in the developing neural tube, Dll1(Delta-like 1) was mainly localized on the processes extending from nascent neurons toward both the pia and the ..

More Information


  1. Hozumi K, Negishi N, Suzuki D, Abe N, Sotomaru Y, Tamaoki N, et al. Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo. Nat Immunol. 2004;5:638-44 pubmed
    ..Here we used the Cre-loxP system to delete the Delta-like 1 gene (Dll1) after birth and demonstrated the complete disappearance of splenic marginal zone B cells in Dll1-null mice...
  2. Hatakeyama J, Wakamatsu Y, Nagafuchi A, Kageyama R, Shigemoto R, Shimamura K. Cadherin-based adhesions in the apical endfoot are required for active Notch signaling to control neurogenesis in vertebrates. Development. 2014;141:1671-82 pubmed publisher
    ..Both Notch1 and its ligand Dll1 are distributed around AJs in the apical endfeet, and these proteins physically interact with ZO-1, a constituent ..
  3. Leimeister C, Dale K, Fischer A, Klamt B, Hrabe de Angelis M, Radtke F, et al. Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors. Dev Biol. 2000;227:91-103 pubmed
    ..Here we show that perturbed Notch signaling in Dll1 and Notch1 knockout mutants affects this expression in the presomitic mesoderm (PSM) and the somites...
  4. Zhang N, Norton C, Gridley T. Segmentation defects of Notch pathway mutants and absence of a synergistic phenotype in lunatic fringe/radical fringe double mutant mice. Genesis. 2002;33:21-8 pubmed
    ..defects are displayed in embryos mutant for the Notch pathway genes Notch1, Lunatic fringe (Lfng), Delta-like 1 (Dll1), and Delta-like 3 (Dll3)...
  5. Mitsiadis T, Fried K, Goridis C. Reactivation of Delta-Notch signaling after injury: complementary expression patterns of ligand and receptor in dental pulp. Exp Cell Res. 1999;246:312-8 pubmed
    ..Here we report on the expression of Notch receptors and the Delta1 ligand in dental pulp of normal and injured adult rat teeth...
  6. Krebs L, Iwai N, Nonaka S, Welsh I, Lan Y, Jiang R, et al. Notch signaling regulates left-right asymmetry determination by inducing Nodal expression. Genes Dev. 2003;17:1207-12 pubmed
    ..Embryos mutant for the Notch ligand Dll1 or doubly mutant for the Notch1 and Notch2 receptors exhibit multiple defects in left-right asymmetry...
  7. Shimizu K, Chiba S, Saito T, Takahashi T, Kumano K, Hamada Y, et al. Integrity of intracellular domain of Notch ligand is indispensable for cleavage required for release of the Notch2 intracellular domain. EMBO J. 2002;21:294-302 pubmed
    ..Here we show that soluble Delta1 (sD1) activates Notch2 (N2), but much more weakly than full-length Delta1 (fD1)...
  8. Wright G, Leslie J, Ariza McNaughton L, Lewis J. Delta proteins and MAGI proteins: an interaction of Notch ligands with intracellular scaffolding molecules and its significance for zebrafish development. Development. 2004;131:5659-69 pubmed
    ..These ATEV Deltas include Delta1 and Delta4 in mammals and DeltaD and DeltaC in the zebrafish...
  9. Stamataki D, Holder M, Hodgetts C, Jeffery R, Nye E, Spencer Dene B, et al. Delta1 expression, cell cycle exit, and commitment to a specific secretory fate coincide within a few hours in the mouse intestinal stem cell system. PLoS ONE. 2011;6:e24484 pubmed publisher
    ..find that secretory cells, and only secretory cells, pass through a phase of strong expression of the Notch ligand Delta1 (Dll1)...
  10. Yang L, Nichols J, Yao C, Manilay J, Robey E, Weinmaster G. Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1. Mol Biol Cell. 2005;16:927-42 pubmed
    ..that expression of mammalian fringe proteins (Lunatic [LFng], Manic [MFng], or Radical [RFng] Fringe) increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells...
  11. Meloty Kapella L, Shergill B, Kuon J, Botvinick E, Weinmaster G. Notch ligand endocytosis generates mechanical pulling force dependent on dynamin, epsins, and actin. Dev Cell. 2012;22:1299-312 pubmed publisher
    ..We propose that the mechanical pulling force produced by endocytosis of Notch-bound ligand drives conformational changes in Notch that permit activating proteolysis. ..
  12. Tanuma S, Shiokawa D. Cloning of a cDNA encoding a rat DNase II-like acid DNase. Biochem Biophys Res Commun. 1999;265:395-9 pubmed
    ..Identification of the full-length cDNA for DLAD would lead to an understanding of the physiology of this DNase II-like molecule. ..
  13. Woo S, Kim J, Han H, Chae J, Son M, Cho S, et al. Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells. BMC Neurosci. 2009;10:97 pubmed publisher
  14. Imai Y, Kobayashi Y, Inoshita T, Meng H, Arano T, Uemura K, et al. The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway. PLoS Genet. 2015;11:e1005503 pubmed publisher
    ..and Notch signaling, through which the LRRK2 complex promotes the recycling of the Notch ligand Delta-like 1 (Dll1)/Delta (Dl) through the modulation of endosomal trafficking...
  15. Nakakura T, Sato M, Suzuki M, Hatano O, Takemori H, Taniguchi Y, et al. The spatial and temporal expression of delta-like protein 1 in the rat pituitary gland during development. Histochem Cell Biol. 2009;131:141-53 pubmed publisher
    ..Similarly, Dlk1 was localized in the cytoplasm of PT cells during development. These findings provide new insights into the mechanism of Dlk1 regarding its regulation of pituitary hormone-secreting cells during development. ..
  16. Watt F. The stem cell compartment in human interfollicular epidermis. J Dermatol Sci. 2002;28:173-80 pubmed
    ..The non-random distribution of stem cells is emphasised and beta1 integrins and Delta1 are suggested to play a role in stem cell patterning...
  17. Zhang L, Widau R, Herring B, Gallagher P. Delta-like 1-Lysine613 regulates notch signaling. Biochim Biophys Acta. 2011;1813:2036-43 pubmed publisher
    ..To identify possible roles for specific lysine residues in the cytoplasmic tail of the Notch ligand Dll1 a mutational and functional analysis was performed...
  18. Favier B, Fliniaux I, Thelu J, Viallet J, Demarchez M, Jahoda C, et al. Localisation of members of the notch system and the differentiation of vibrissa hair follicles: receptors, ligands, and fringe modulators. Dev Dyn. 2000;218:426-37 pubmed
    ..The results show that two receptors, Notch1 and -2, three ligands, Delta1, Serrate1, and -2, and the three Fringe regulators, Lunatic, Manic, and Radical, are expressed in different ..
  19. Estrach S, Cordes R, Hozumi K, Gossler A, Watt F. Role of the Notch ligand Delta1 in embryonic and adult mouse epidermis. J Invest Dermatol. 2008;128:825-32 pubmed
    The Notch ligand Delta1 (Dll1) is expressed in human interfollicular epidermis (IFE) and regulates differentiation and adhesion of cultured human keratinocytes...
  20. Beckers J, Clark A, Wunsch K, Hrabe de Angelis M, Gossler A. Expression of the mouse Delta1 gene during organogenesis and fetal development. Mech Dev. 1999;84:165-8 pubmed
    ..Mouse Delta1 (delta-like 1; Dll1) encodes one of the four known mammalian DSL proteins and is essential for normal ..
  21. Lindsell C, Boulter J, diSibio G, Gossler A, Weinmaster G. Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development. Mol Cell Neurosci. 1996;8:14-27 pubmed
    ..Furthermore, within the ventricular zone of the neural tube and retina, Jagged and Delta 1 were expressed in complementary regions, suggesting that different DSL-Notch combinations may direct the development of distinct neural subtypes. ..
  22. Le Friec G, Sheppard D, Whiteman P, Karsten C, Shamoun S, Laing A, et al. The CD46-Jagged1 interaction is critical for human TH1 immunity. Nat Immunol. 2012;13:1213-21 pubmed publisher
  23. Czajkowski M, Rassek C, Lenhard D, Bröhl D, Birchmeier C. Divergent and conserved roles of Dll1 signaling in development of craniofacial and trunk muscle. Dev Biol. 2014;395:307-16 pubmed publisher
    ..We show here that the pool of myogenic progenitor cells in craniofacial muscle of Dll1(LacZ/Ki) mutant mice is depleted in early fetal development, which is accompanied by a major deficit in muscle ..
  24. Schuster Gossler K, Cordes R, Gossler A. Premature myogenic differentiation and depletion of progenitor cells cause severe muscle hypotrophy in Delta1 mutants. Proc Natl Acad Sci U S A. 2007;104:537-42 pubmed
    ..We show that in mouse embryos the Notch ligand Delta1 (Dll1) controls both differentiation of early myoblasts and maintenance of myogenic progenitor cells...
  25. Ivey K, Muth A, Arnold J, King F, Yeh R, Fish J, et al. MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell. 2008;2:219-29 pubmed publisher
    ..Our findings indicate that muscle-specific miRNAs reinforce the silencing of nonmuscle genes during cell lineage commitment and suggest that miRNAs may have general utility in regulating cell-fate decisions from pluripotent ES cells. ..
  26. Preuße K, Tveriakhina L, Schuster Gossler K, Gaspar C, Rosa A, Henrique D, et al. Context-Dependent Functional Divergence of the Notch Ligands DLL1 and DLL4 In Vivo. PLoS Genet. 2015;11:e1005328 pubmed publisher
    ..Among the ligands are two Delta paralogues, DLL1 and DLL4, that are conserved in mammals and share a similar structure and sequence...
  27. Shimizu K, Chiba S, Hosoya N, Kumano K, Saito T, Kurokawa M, et al. Binding of Delta1, Jagged1, and Jagged2 to Notch2 rapidly induces cleavage, nuclear translocation, and hyperphosphorylation of Notch2. Mol Cell Biol. 2000;20:6913-22 pubmed
    b>Delta1, Jagged1, and Jagged2, commonly designated Delta/Serrate/LAG-2 (DSL) proteins, are known to be ligands for Notch1. However, it has been less understood whether they are ligands for Notch receptors other than Notch1...
  28. Napp L, Augustynik M, Paesler F, Krishnasamy K, Woiterski J, Limbourg A, et al. Extrinsic Notch ligand Delta-like 1 regulates tip cell selection and vascular branching morphogenesis. Circ Res. 2012;110:530-5 pubmed publisher
    ..Tip cell differentiation is inhibited through lateral Notch signaling between ECs, which is controlled by Notch ligands expressed in vessel sprouts. The contribution of the Notch ligand Delta-like (Dll) 1 herein is unknown...
  29. Ahnfelt Rønne J, Jørgensen M, Klinck R, Jensen J, Füchtbauer E, Deering T, et al. Ptf1a-mediated control of Dll1 reveals an alternative to the lateral inhibition mechanism. Development. 2012;139:33-45 pubmed publisher
    Neurog3-induced Dll1 expression in pancreatic endocrine progenitors ostensibly activates Hes1 expression via Notch and thereby represses Neurog3 and endocrine differentiation in neighboring cells by lateral inhibition...
  30. Piggott K, Deng J, Warrington K, Younge B, Kubo J, Desai M, et al. Blocking the NOTCH pathway inhibits vascular inflammation in large-vessel vasculitis. Circulation. 2011;123:309-18 pubmed publisher
    ..temporal arteries revealed abundant expression of the NOTCH receptor and its ligands, Jagged1 and Delta1. Cleavage of the NOTCH intracellular domain in wall-infiltrating T cells indicated ongoing NOTCH pathway ..
  31. Apelqvist A, Li H, Sommer L, Beatus P, Anderson D, Honjo T, et al. Notch signalling controls pancreatic cell differentiation. Nature. 1999;400:877-81 pubmed
    ..Mice deficient for Delta-like gene 1 (Dll1) or the intracellular mediator RBP-Jkappa showed accelerated differentiation of pancreatic endocrine cells...
  32. Okubo Y, Sugawara T, Abe Koduka N, Kanno J, Kimura A, Saga Y. Lfng regulates the synchronized oscillation of the mouse segmentation clock via trans-repression of Notch signalling. Nat Commun. 2012;3:1141 pubmed publisher
    ..Here we show, using chimeric embryos composed of wild-type cells and Delta like 1 (Dll1)-null cells, that Dll1-mediated Notch signalling is responsible for the synchronization mechanism...
  33. Cao Q, Lu J, Kaur C, Sivakumar V, Li F, Cheah P, et al. Expression of Notch-1 receptor and its ligands Jagged-1 and Delta-1 in amoeboid microglia in postnatal rat brain and murine BV-2 cells. Glia. 2008;56:1224-37 pubmed publisher
    ..It is concluded that Notch-1 signaling in the AMC and LPS-activated microglia/BV-2 cells modulates the expression of proinflammatory cytokines and nitric oxide. ..
  34. Elyaman W, Bradshaw E, Wang Y, Oukka M, Kivisakk P, Chiba S, et al. JAGGED1 and delta1 differentially regulate the outcome of experimental autoimmune encephalomyelitis. J Immunol. 2007;179:5990-8 pubmed
    ..We investigated the role of Jagged1 and Delta1 in experimental autoimmune encephalomyelitis...
  35. Tan J, Xu K, Cretegny K, Visan I, Yuan J, Egan S, et al. Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches. Immunity. 2009;30:254-63 pubmed publisher
    ..Our study has revealed that the Fringe-Notch2 interaction has important functions in vivo and provides insights into mechanisms regulating MZ B cell development. ..
  36. Liu Z, Chen S, Boyle S, Zhu Y, Zhang A, Piwnica Worms D, et al. The extracellular domain of Notch2 increases its cell-surface abundance and ligand responsiveness during kidney development. Dev Cell. 2013;25:585-98 pubmed publisher
    ..This context-specific asymmetry in NICD release efficiency is further enhanced by Fringe. Our results indicate that an elevated N1 surface level could compensate for the loss of N2 signal in specific cell contexts. ..
  37. Rubio Aliaga I, Przemeck G, Fuchs H, Gailus Durner V, Adler T, Hans W, et al. Dll1 haploinsufficiency in adult mice leads to a complex phenotype affecting metabolic and immunological processes. PLoS ONE. 2009;4:e6054 pubmed publisher
    ..Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood...
  38. Hiraoka Y, Komine O, Nagaoka M, Bai N, Hozumi K, Tanaka K. Delta-like 1 regulates Bergmann glial monolayer formation during cerebellar development. Mol Brain. 2013;6:25 pubmed publisher
    ..However, it remains to be determined which ligand activates Nocth1 and Notch 2 on BG. Delta-like 1 (Dll1) is a major ligand of Notch receptors that is expressed in the developing cerebellum...
  39. Sörensen I, Adams R, Gossler A. DLL1-mediated Notch activation regulates endothelial identity in mouse fetal arteries. Blood. 2009;113:5680-8 pubmed publisher
    ..However, a specific role of the ligand Delta-like 1 (DLL1) has not been shown thus far...
  40. Bröhl D, Vasyutina E, Czajkowski M, Griger J, Rassek C, Rahn H, et al. Colonization of the satellite cell niche by skeletal muscle progenitor cells depends on Notch signals. Dev Cell. 2012;23:469-81 pubmed publisher
    ..We conclude that Notch signals control homing of satellite cells, stimulating them to contribute to their own microenvironment and to adhere to myofibers. ..
  41. Kawaguchi D, Furutachi S, Kawai H, Hozumi K, Gotoh Y. Dll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis. Nat Commun. 2013;4:1880 pubmed publisher
    ..Here we show that the Notch ligand Delta-like 1 (Dll1) is required to maintain quiescent NSCs in the adult mouse subventricular zone...
  42. Shimizu K, Chiba S, Saito T, Kumano K, Hirai H. Physical interaction of Delta1, Jagged1, and Jagged2 with Notch1 and Notch3 receptors. Biochem Biophys Res Commun. 2000;276:385-9 pubmed
    The Delta/Serrate/LAG-2 (DSL) domain-containing proteins, Delta1, Jagged1, and Jagged2, are considered to be ligands for Notch receptors...
  43. Jaleco A, Neves H, Hooijberg E, Gameiro P, Clode N, Haury M, et al. Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation. J Exp Med. 2001;194:991-1002 pubmed
    ..Our results thus indicate that distinct Notch ligands can mediate differential effects of Notch signaling and provide a useful system to further address cell-fate decision processes in lymphopoiesis. ..
  44. de Pooter R, Schmitt T, de la Pompa J, Fujiwara Y, Orkin S, Zuniga Pflucker J. Notch signaling requires GATA-2 to inhibit myelopoiesis from embryonic stem cells and primary hemopoietic progenitors. J Immunol. 2006;176:5267-75 pubmed
    ..Taken together, our results support a role for GATA-2 in allowing Dll-1 to restrict non-T cell lineage differentiation outcomes. ..
  45. Ozbey O, Sahin Z, Ozenci A, Acar N, Ustunel I. The effect of systemic corticosteroid treatment on the immunolocalisation of Notch-1, Delta, CD105 and CD166 in rat articular cartilage. Acta Histochem. 2010;112:424-31 pubmed publisher
  46. Kakuda S, Haltiwanger R. Deciphering the Fringe-Mediated Notch Code: Identification of Activating and Inhibiting Sites Allowing Discrimination between Ligands. Dev Cell. 2017;40:193-201 pubmed publisher
    ..Combined, these results suggest that Fringe modifications "mark" different regions in the Notch1 extracellular domain for activation or inhibition. ..
  47. Heuss S, Ndiaye Lobry D, Six E, Israel A, Logeat F. The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity. Proc Natl Acad Sci U S A. 2008;105:11212-7 pubmed publisher
    ..Here, we show that an ubiquitination-defective mutant of the murine Delta-homologue Dll1 is endocytosed but, in contrast to the wild-type Dll1, is unable to subsequently recycle back to the cell surface ..
  48. Horn S, Kobberup S, Jørgensen M, Kalisz M, Klein T, Kageyama R, et al. Mind bomb 1 is required for pancreatic ?-cell formation. Proc Natl Acad Sci U S A. 2012;109:7356-61 pubmed publisher
    ..Our results reveal iterative use of Notch in pancreatic development to ensure correct P-D patterning and adequate ?-cell formation. ..
  49. Su Y, Buchler P, Gazdhar A, Giese N, Reber H, Hines O, et al. Pancreatic regeneration in chronic pancreatitis requires activation of the notch signaling pathway. J Gastrointest Surg. 2006;10:1230-41; discussion 1242 pubmed
    ..These findings suggest a possible role of the Notch pathway during pancreatic regeneration since Jagged-1 inhibits inducible collagen-1 production, suggesting a new mechanism of tissue repair in this disease. ..
  50. Morimoto M, Takahashi Y, Endo M, Saga Y. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity. Nature. 2005;435:354-9 pubmed
    ..We propose that the oscillation of Notch activity is arrested and translated in the wavefront by Mesp2. ..
  51. Mitsiadis T, Hirsinger E, Lendahl U, Goridis C. Delta-notch signaling in odontogenesis: correlation with cytodifferentiation and evidence for feedback regulation. Dev Biol. 1998;204:420-31 pubmed
    ..Here we report on the expression and regulation of Delta1, a transmembrane ligand of the Notch receptors, during mouse odontogenesis...
  52. Lewis A, Frantz G, Carpenter D, de Sauvage F, Gao W. Distinct expression patterns of notch family receptors and ligands during development of the mammalian inner ear. Mech Dev. 1998;78:159-63 pubmed
    ..expression of genes in the Notch signaling pathway, Notch receptors (Notch1-4) and two ligands, Jagged1 and Delta1, in the developing mammalian inner ear...