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Gene Review

Dll1  -  delta-like 1 (Drosophila)

Mus musculus

Synonyms: Delta-like protein 1, Delta1, Drosophila Delta homolog 1
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Disease relevance of Dll1

  • Interestingly, absence of Delta-1 leads to diminution of both neurons and glia in peripheral ganglia, suggesting a general depletion of the ganglion precursor pool in mutant mice [1].
  • Although titers of WT and Delta cmaA2 organisms were identical during mouse infection, Delta cmaA2 bacteria were hypervirulent while inducing larger granulomas than WT M. tuberculosis [2].
  • Mutations in the DSL (Delta, Serrate, Lag2) Notch (N) ligand Delta-like (Dll) 3 cause skeletal abnormalities in spondylocostal dysostosis, which is consistent with a critical role for N signaling during somitogenesis [3].
  • Notch pathway inhibition with soluble Delta ligand or gamma secretase inhibitors resulted in a marked reduction of viable cell numbers in medulloblastoma cell lines and primary tumor cultures [4].
  • To address this issue, we compared the susceptibility of Mttp(Delta/Delta) mice and Mttp(flox/flox) controls to hepatic injury from Escherichia coli lipopolysaccharides, concanavalin A, and Pseudomonas aeruginosa exotoxin A [5].

Psychiatry related information on Dll1

  • In control mice, sleep deprivation induced a rise of coherence in the Delta band of NREM sleep in the first 2 h of recovery [6].
  • With the availability of the highly selective, nonequilibrium delta-1 opioid receptor antagonist, [D-Ala2,Leu5,Cys6]enkephalin, it was possible, in the present report, to examine the possible involvement of delta-1 opioid receptors in the development of opiate dependence [7].
  • Antinociception was evaluated by the increase in reaction time difference (Delta latency), between readings obtained before and after the administration of drugs [8].
  • The present investigation evaluated alcohol-drinking behaviors in mice that are haplodeficient in CREB as a result of targeted CREB (alpha and Delta) gene disruption [9].

High impact information on Dll1

  • The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries [10].
  • An alternative mechanism for the expression of the delta gene is found in hybridoma B1-8. delta 1, which actively secretes delta chains and synthesizes no mu chain [11].
  • Here we report that, in Dll1-deficient mouse embryos, a primary metameric pattern is established in mesoderm, and cytodifferentiation is apparently normal, but the segments have no cranio-caudal polarity, and no epithelial somites form [12].
  • These results show that Dll1 is involved in compartmentalization of somites, that dermomyotome and sclerotome differentiation are independent of formation of epithelia and subdivision of somites in cranial and caudal halves, and that compartmentalization is essential for the maintenance of segment borders in paraxial mesoderm-derived structures [12].
  • The TCR expressed by this gamma delta T-cell subset consists of the same V delta 1 chain [13].

Chemical compound and disease context of Dll1


Biological context of Dll1

  • We show, that the loss-of-function of the delta 1 (Dll1) gene causes a situs ambiguous phenotype, including randomisation of the direction of heart looping and embryonic turning [19].
  • Dll1 expression in the paraxial mesoderm and nervous system is strikingly similar to the expression of mouse Notch1 during gastrulation and early organogenesis [20].
  • Moreover, analyses of the lungs from the gene-targeted mice suggested that expression of Delta-like 1 (Dll1 - Mouse Genome Informatics) mRNA depends on Mash1 [21].
  • However, Math1-null rhombic lip cells presented conspicuous downregulation of Notch4 and Dll1 [22].
  • Identification of Dll1 (Delta1) target genes during mouse embryogenesis using differential expression profiling [23].

Anatomical context of Dll1

  • The defects in RC polarity were determined by the altered expressions of Uncx4.1 and Dll1 in the segmented somites and presomitic mesoderm, respectively [24].
  • In the absence of Dll1, auditory hair cells develop early and in excess, in agreement with the lateral inhibition hypothesis [25].
  • Notch2, Notch3, and Dll1 are initially expressed by most cells within the pituitary primordium and become restricted to a subset of the progenitor cell pool as differentiated pituitary cells begin to appear [26].
  • In the normal thymus anlages on embryonic day 13, Dll4 is strongly expressed throughout the epithelial region, but Dll1 is expressed only in scattered cells [27].
  • In contrast, epithelial cells of the nude thymus anlages express neither Dll1 nor Dll4 [27].

Associations of Dll1 with chemical compounds


Physical interactions of Dll1


Enzymatic interactions of Dll1

  • We show that full-length Notch1 [N1(FL)] transfected into wild type (WT) primary neurons is cleaved in the presence of its biological ligand Delta (Dl) and translocated to the nucleus within 1--3 min of ligand addition [33].

Regulatory relationships of Dll1

  • Our results indicate that WNT activity, in synergy with TBX6, regulates Dll1 transcription and thereby controls Notch activity, somite formation, and patterning [34].
  • Expression of c-fos in cortex and cingulate gyrus was enhanced in beta-APPDelta/Delta mice, although the amount of structural damage and apoptosis in the hippocampal pyramidal cell layer and cortex was similar to that of controls [30].
  • Opposite role of delta 1- and delta 2-opioid receptors activated by endogenous or exogenous opioid agonists on the endogenous cholecystokinin system: further evidence for delta-opioid receptor heterogeneity [35].

Other interactions of Dll1

  • The Delta-Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for cell fate specification [36].
  • Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear [25].
  • We hypothesise that Dll1 is involved in the release of cells from the precursor population and that Dll3 is required later to divert neurons along a specific differentiation pathway [37].
  • The level of Dll1 transcripts is also increased in the presomitic mesoderm of PS1(-/-) embryos, while the level of Notch1 transcripts is unchanged, in contrast to a previous report (Wong et al., 1997, Nature 387, 288-292) [38].
  • Expression of Jagged2 and Delta1 seldom was affected by the stimuli [39].

Analytical, diagnostic and therapeutic context of Dll1


  1. Disruption of segmental neural crest migration and ephrin expression in delta-1 null mice. De Bellard, M.E., Ching, W., Gossler, A., Bronner-Fraser, M. Dev. Biol. (2002) [Pubmed]
  2. Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis -induced inflammation and virulence. Rao, V., Gao, F., Chen, B., Jacobs, W.R., Glickman, M.S. J. Clin. Invest. (2006) [Pubmed]
  3. The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands. Ladi, E., Nichols, J.T., Ge, W., Miyamoto, A., Yao, C., Yang, L.T., Boulter, J., Sun, Y.E., Kintner, C., Weinmaster, G. J. Cell Biol. (2005) [Pubmed]
  4. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Hallahan, A.R., Pritchard, J.I., Hansen, S., Benson, M., Stoeck, J., Hatton, B.A., Russell, T.L., Ellenbogen, R.G., Bernstein, I.D., Beachy, P.A., Olson, J.M. Cancer Res. (2004) [Pubmed]
  5. Blocking the secretion of hepatic very low density lipoproteins renders the liver more susceptible to toxin-induced injury. Björkegren, J., Beigneux, A., Bergo, M.O., Maher, J.J., Young, S.G. J. Biol. Chem. (2002) [Pubmed]
  6. Interhemispheric coherence of the sleep electroencephalogram in mice with congenital callosal dysgenesis. Vyazovskiy, V., Achermann, P., Borbély, A.A., Tobler, I. Neuroscience (2004) [Pubmed]
  7. Lack of involvement of delta-1 opioid receptors in the development of physical dependence on morphine in mice. Miyamoto, Y., Bowen, W.D., Portoghese, P.S., Takemori, A.E. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  8. Atropine reverses the antinociception of nonsteroidal anti-inflammatory drugs in the tail-flick test of mice. Pinardi, G., Sierralta, F., Miranda, H.F. Pharmacol. Biochem. Behav. (2003) [Pubmed]
  9. Partial deletion of the cAMP response element-binding protein gene promotes alcohol-drinking behaviors. Pandey, S.C., Roy, A., Zhang, H., Xu, T. J. Neurosci. (2004) [Pubmed]
  10. The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries. Kusumi, K., Sun, E.S., Kerrebrock, A.W., Bronson, R.T., Chi, D.C., Bulotsky, M.S., Spencer, J.B., Birren, B.W., Frankel, W.N., Lander, E.S. Nat. Genet. (1998) [Pubmed]
  11. The role of DNA rearrangement and alternative RNA processing in the expression of immunoglobulin delta genes. Maki, R., Roeder, W., Traunecker, A., Sidman, C., Wabl, M., Raschke, W., Tonegawa, S. Cell (1981) [Pubmed]
  12. Maintenance of somite borders in mice requires the Delta homologue DII1. Hrabĕ de Angelis, M., McIntyre, J., Gossler, A. Nature (1997) [Pubmed]
  13. Homing of a gamma delta thymocyte subset with homogeneous T-cell receptors to mucosal epithelia. Itohara, S., Farr, A.G., Lafaille, J.J., Bonneville, M., Takagaki, Y., Haas, W., Tonegawa, S. Nature (1990) [Pubmed]
  14. Novel lymphotoxin alpha (LTalpha) knockout mice with unperturbed tumor necrosis factor expression: reassessing LTalpha biological functions. Liepinsh, D.J., Grivennikov, S.I., Klarmann, K.D., Lagarkova, M.A., Drutskaya, M.S., Lockett, S.J., Tessarollo, L., McAuliffe, M., Keller, J.R., Kuprash, D.V., Nedospasov, S.A. Mol. Cell. Biol. (2006) [Pubmed]
  15. Switching species tropism: an effective way to manipulate the feline coronavirus genome. Haijema, B.J., Volders, H., Rottier, P.J. J. Virol. (2003) [Pubmed]
  16. Calcineurin is essential for virulence in Candida albicans. Bader, T., Bodendorfer, B., Schröppel, K., Morschhäuser, J. Infect. Immun. (2003) [Pubmed]
  17. Constitutive and inducible expression of CYP enzymes in immortal hepatocytes derived from SV40 transgenic mice. Donato, M.T., Klocke, R., Castell, J.V., Stenzel, K., Paul, D., Gómez-Lechón, M.J. Xenobiotica (2003) [Pubmed]
  18. Neuronal nitric oxide synthase activation and peroxynitrite formation in ischemic stroke linked to neural damage. Eliasson, M.J., Huang, Z., Ferrante, R.J., Sasamata, M., Molliver, M.E., Snyder, S.H., Moskowitz, M.A. J. Neurosci. (1999) [Pubmed]
  19. Node and midline defects are associated with left-right development in Delta1 mutant embryos. Przemeck, G.K., Heinzmann, U., Beckers, J., Hrabé de Angelis, M. Development (2003) [Pubmed]
  20. Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta. Bettenhausen, B., Hrabĕ de Angelis, M., Simon, D., Guénet, J.L., Gossler, A. Development (1995) [Pubmed]
  21. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Ito, T., Udaka, N., Yazawa, T., Okudela, K., Hayashi, H., Sudo, T., Guillemot, F., Kageyama, R., Kitamura, H. Development (2000) [Pubmed]
  22. Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway. Gazit, R., Krizhanovsky, V., Ben-Arie, N. Development (2004) [Pubmed]
  23. Identification of Dll1 (Delta1) target genes during mouse embryogenesis using differential expression profiling. Machka, C., Kersten, M., Zobawa, M., Harder, A., Horsch, M., Halder, T., Lottspeich, F., Hrabé de Angelis, M., Beckers, J. Gene Expr. Patterns (2005) [Pubmed]
  24. Hypomorphic Mesp allele distinguishes establishment of rostrocaudal polarity and segment border formation in somitogenesis. Nomura-Kitabayashi, A., Takahashi, Y., Kitajima, S., Inoue, T., Takeda, H., Saga, Y. Development (2002) [Pubmed]
  25. Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear. Brooker, R., Hozumi, K., Lewis, J. Development (2006) [Pubmed]
  26. Developmental regulation of Notch signaling genes in the embryonic pituitary: Prop1 deficiency affects Notch2 expression. Raetzman, L.T., Ross, S.A., Cook, S., Dunwoodie, S.L., Camper, S.A., Thomas, P.Q. Dev. Biol. (2004) [Pubmed]
  27. Lack of Delta like 1 and 4 expressions in nude thymus anlages. Tsukamoto, N., Itoi, M., Nishikawa, M., Amagai, T. Cell. Immunol. (2005) [Pubmed]
  28. Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Ciofani, M., Zúñiga-Pflücker, J.C. Nat. Immunol. (2005) [Pubmed]
  29. Pax-6 and lens-specific transcription of the chicken delta 1-crystallin gene. Cvekl, A., Sax, C.M., Li, X., McDermott, J.B., Piatigorsky, J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  30. Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Steinbach, J.P., Müller, U., Leist, M., Li, Z.W., Nicotera, P., Aguzzi, A. Cell Death Differ. (1998) [Pubmed]
  31. Dll1 is a downstream target of Tbx6 in the paraxial mesoderm. White, P.H., Chapman, D.L. Genesis (2005) [Pubmed]
  32. Syntenin mediates Delta1-induced cohesiveness of epidermal stem cells in culture. Estrach, S., Legg, J., Watt, F.M. J. Cell. Sci. (2007) [Pubmed]
  33. Effect of PS1 deficiency and an APP gamma-secretase inhibitor on Notch1 signaling in primary mammalian neurons. Jack, C., Berezovska, O., Wolfe, M.S., Hyman, B.T. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  34. WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos. Hofmann, M., Schuster-Gossler, K., Watabe-Rudolph, M., Aulehla, A., Herrmann, B.G., Gossler, A. Genes Dev. (2004) [Pubmed]
  35. Opposite role of delta 1- and delta 2-opioid receptors activated by endogenous or exogenous opioid agonists on the endogenous cholecystokinin system: further evidence for delta-opioid receptor heterogeneity. Noble, F., Fournie-Zaluski, M.C., Roques, B.P. Neuroscience (1996) [Pubmed]
  36. Mind bomb 1 is essential for generating functional Notch ligands to activate Notch. Koo, B.K., Lim, H.S., Song, R., Yoon, M.J., Yoon, K.J., Moon, J.S., Kim, Y.W., Kwon, M.C., Yoo, K.W., Kong, M.P., Lee, J., Chitnis, A.B., Kim, C.H., Kong, Y.Y. Development (2005) [Pubmed]
  37. Mouse Dll3: a novel divergent Delta gene which may complement the function of other Delta homologues during early pattern formation in the mouse embryo. Dunwoodie, S.L., Henrique, D., Harrison, S.M., Beddington, R.S. Development (1997) [Pubmed]
  38. Presenilin-1 regulates neuronal differentiation during neurogenesis. Handler, M., Yang, X., Shen, J. Development (2000) [Pubmed]
  39. Expression of Jagged1 gene in macrophages and its regulation by hematopoietic growth factors. Nomaguchi, K., Suzu, S., Yamada, M., Hayasawa, H., Motoyoshi, K. Exp. Hematol. (2001) [Pubmed]
  40. Linked suppression in peripheral T cell tolerance to the house dust mite derived allergen Der p 1. Hoyne, G.F., Dallman, M.J., Lamb, J.R. Int. Arch. Allergy Immunol. (1999) [Pubmed]
  41. Notch ligation by Delta1 inhibits peripheral immune responses to transplantation antigens by a CD8+ cell-dependent mechanism. Wong, K.K., Carpenter, M.J., Young, L.L., Walker, S.J., McKenzie, G., Rust, A.J., Ward, G., Packwood, L., Wahl, K., Delriviere, L., Hoyne, G., Gibbs, P., Champion, B.R., Lamb, J.R., Dallman, M.J. J. Clin. Invest. (2003) [Pubmed]
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