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Gene Review

Dl  -  Delta

Drosophila melanogaster

Synonyms: 0495/20, 0926/11, 1053/14, 1119/09, 1304/03, ...
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Disease relevance of Dl

  • We now show that Drosophila Delta proteolysis occurs independent of and prior to endocytosis in neuroblasts and ganglion mother cells in vivo and cells in culture [1].
  • Furthermore, Delta expression during oogenesis can be correlated with a number of morphogenetic defects associated with sterility observed in Dl mutant females, including failure of stalk formation within the germarium and subsequent fusion of egg chambers, necrosis in germ-line cells, and multiphasic embryonic arrest of fertilized eggs [2].
  • To demonstrate this, we targeted the promoter of the well-characterized fushi tarazu (ftz) gene with a ZFP TF activator using the VP16 activation domain from Herpes simplex virus, and ZFP TF repressors using the Drosophila methyl-CpG binding domain (MBD)-like Delta protein [3].
  • BACKGROUND: On the basis of experiments suggesting that Notch and Delta have a role in axonal development in Drosophila neurons, we studied the ability of components of the Notch signaling pathway to modulate neurite formation in mammalian neuroblastoma cells in vitro [4].
  • Among the extant mutations in these seven loci, only mutations in Dl lead to the so-called neurogenic phenotype: hypertrophy of the nervous system and reduction of the epidermis [5].

High impact information on Dl


Biological context of Dl

  • Removal of both Dl and Ser, however, led to cell fate transformations similar to the N phenotype [9].
  • Part of a cross-hybridizing cDNA clone, derived from a gene located at position 95F on the third chromosome, was sequenced and found to encode five repeats with homology to those encoded by N and Dl [10].
  • Sequencing of this Dl fragment revealed an open reading frame encoding four EGF-like repeats with homology to the repeats found in the N gene [10].
  • Screening genomic and cDNA libraries under conditions of reduced stringency with Dl and N probes that encode EGF-like repeats uncovered several cross-hybridizing clones, suggesting that other Drosophila genes may also encode such peptides [10].
  • Some aspects of the pattern of Dl protein appeared to be due to endocytosis [11].

Anatomical context of Dl

  • N and Dl protein levels were assessed in the cell as a whole and at the cell surface, where these proteins were mostly found at the intercellular cell junctions [11].
  • Here, we found N, Dl, and Ser were mostly located in the region from the subapical complex (SAC) to the apical portion of the adherens junctions (AJs) in wing disc epithelium [12].
  • We demonstrate that while Lqf is necessary for three different Notch/Delta signaling events at the morphogenetic furrow, Faf is essential only for one: Delta signaling by photoreceptor precluster cells, which prevents recruitment of ectopic neurons [13].
  • We have addressed the snail-dependent regulation of Delta trafficking during the plasma membrane growth of the mesoderm in the Drosophila embryo [14].
  • We show that Delta is retained in endocytic vesicles in the mesoderm but expressed on the surface of the adjacent ectoderm [14].

Associations of Dl with chemical compounds

  • Consistent with this notion, Gp150 is co-localized with Delta in intracellular vesicles in cells within the MF region and loss of gp150 function causes accumulation of intracellular Delta protein [15].
  • In situ hybridization using digoxigenin-labelled probes confirms that Delta RNA is present at high concentration in all presumptive neurogenic territories of the embryo [16].
  • The isolated cDNA encoded a transmembrane protein with a Delta/Serrate/LAG-2 domain, 16 epidermal growth factor-like repeats and a cysteine-rich region [17].
  • We find that different alleles of the highly mutable recessive lethal complementation group, l(4)2, also have defects in different parts of the projectin sequence, both NH2-terminal and COOH-terminal to the bentD breakpoint [18].
  • Further complementation analyses between latheoP1 and lethal alleles, produced by excision of the latheoP1 insert or by EMS or gamma-rays, in the 49F region mapped the latheo mutation to one vital complementation group [19].

Physical interactions of Dl

  • Abruptex[M1] showed less activity than wild-type Notch in its ability to bind Delta and Serrate and was expressed at reduced levels on the cell surface [20].
  • Deletion of the Brd gene complex results in ectopic endocytosis of Dl in dorsal cells of stage 5 embryos [21].
  • We describe a mechanism by which the Ebi/SMRTER corepressor complex maintains Dl expression [22].
  • Alleles of a lethal complementation group exhibit a complex pattern of complementation with Pas alleles [23].

Enzymatic interactions of Dl

  • Kul cleaves Dl efficiently both in cell culture and in flies, and has previously been shown not to be necessary for Notch processing during signaling [24].

Regulatory relationships of Dl

  • Unidirectional signaling from cells expressing Delta (Dl) to cells expressing Notch is a key feature of many developmental processes [24].
  • Snail represses Tom expression in the mesoderm and thereby activates Delta trafficking [14].
  • Thus the extra wing vein phenotype of ed is enhanced upon reduction of Delta (Dl) or Enhancer of split [E(spl)] proteins [25].
  • We provide evidence that, at the onset of wing development, Delta is under the control of apterous and might be the Notch ligand in this process [26].
  • This phenotype is suppressed by overexpression of E(spl)m7 and enhanced by overexpression of Dl [25].

Other interactions of Dl

  • This is achieved by fng through a cell-autonomous mechanism that inhibits a cell's ability to respond to Serrate protein and potentiates its ability to respond to Delta protein [27].
  • We provide evidence that Notch activation by its ligand Delta is the second Hh-dependent signal required for neural determination [28].
  • We propose that Faf plays a role similar to that of Neur in the Delta signaling cells [13].
  • Moreover, in the ovary da- alleles exhibit dominant synergistic interactions with N or Dl mutations [29].
  • Deciphering synergistic and redundant roles of Hedgehog, Decapentaplegic and Delta that drive the wave of differentiation in Drosophila eye development [30].

Analytical, diagnostic and therapeutic context of Dl

  • We developed a protocol based on chromosomal deletion and microarray analysis that led to the identification of tom as the target of snail regulating Delta trafficking [14].
  • The basis for the genetic antimorphism of NM1 seems to reside in the titration of Notch wild-type products into NM1/N+ nonfunctional dimers and/or the titration of Delta products into nonfunctional ligand-receptor complexes [31].
  • Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand [32].
  • To investigate the role of Edd in vivo, gene targeting was used to generate Edd knockout (Edd(Delta/Delta)) mice [33].
  • Various kinds of data, in particular from cell transplantation studies and from genetic and molecular analyses, suggest that the proteins encoded by the genes Notch and Delta interact at the membrane of the neuroectodermal cells to provide a regulatory signal [34].


  1. Endocytosis-independent mechanisms of Delta ligand proteolysis. Delwig, A., Bland, C., Beem-Miller, M., Kimberly, P., Rand, M.D. Exp. Cell Res. (2006) [Pubmed]
  2. Complex function and expression of Delta during Drosophila oogenesis. Bender, L.B., Kooh, P.J., Muskavitch, M.A. Genetics (1993) [Pubmed]
  3. Controlling gene expression in Drosophila using engineered zinc finger protein transcription factors. Jamieson, A.C., Guan, B., Cradick, T.J., Xiao, H., Holmes, M.C., Gregory, P.D., Carroll, P.M. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  4. Autonomous and non-autonomous regulation of mammalian neurite development by Notch1 and Delta1. Franklin, J.L., Berechid, B.E., Cutting, F.B., Presente, A., Chambers, C.B., Foltz, D.R., Ferreira, A., Nye, J.S. Curr. Biol. (1999) [Pubmed]
  5. Cytogenetic definition and morphogenetic analysis of Delta, a gene affecting neurogenesis in Drosophila melanogaster. Alton, A.K., Fechtel, K., Terry, A.L., Meikle, S.B., Muskavitch, M.A. Genetics (1988) [Pubmed]
  6. Asymmetric Rab 11 endosomes regulate delta recycling and specify cell fate in the Drosophila nervous system. Emery, G., Hutterer, A., Berdnik, D., Mayer, B., Wirtz-Peitz, F., Gaitan, M.G., Knoblich, J.A. Cell (2005) [Pubmed]
  7. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Glover, D.M., Leibowitz, M.H., McLean, D.A., Parry, H. Cell (1995) [Pubmed]
  8. Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila. Ruohola, H., Bremer, K.A., Baker, D., Swedlow, J.R., Jan, L.Y., Jan, Y.N. Cell (1991) [Pubmed]
  9. Delta and Serrate are redundant Notch ligands required for asymmetric cell divisions within the Drosophila sensory organ lineage. Zeng, C., Younger-Shepherd, S., Jan, L.Y., Jan, Y.N. Genes Dev. (1998) [Pubmed]
  10. EGF homologous sequences encoded in the genome of Drosophila melanogaster, and their relation to neurogenic genes. Knust, E., Dietrich, U., Tepass, U., Bremer, K.A., Weigel, D., Vässin, H., Campos-Ortega, J.A. EMBO J. (1987) [Pubmed]
  11. The R8-photoreceptor equivalence group in Drosophila: fate choice precedes regulated Delta transcription and is independent of Notch gene dose. Baker, N.E., Yu, S.Y. Mech. Dev. (1998) [Pubmed]
  12. Polarized exocytosis and transcytosis of Notch during its apical localization in Drosophila epithelial cells. Sasaki, N., Sasamura, T., Ishikawa, H.O., Kanai, M., Ueda, R., Saigo, K., Matsuno, K. Genes Cells (2007) [Pubmed]
  13. Fat facets and Liquid facets promote Delta endocytosis and Delta signaling in the signaling cells. Overstreet, E., Fitch, E., Fischer, J.A. Development (2004) [Pubmed]
  14. Dorsal-ventral pattern of Delta trafficking is established by a Snail-Tom-Neuralized pathway. De Renzis, S., Yu, J., Zinzen, R., Wieschaus, E. Dev. Cell (2006) [Pubmed]
  15. Drosophila Gp150 is required for early ommatidial development through modulation of Notch signaling. Fetchko, M., Huang, W., Li, Y., Lai, Z.C. EMBO J. (2002) [Pubmed]
  16. The pattern of transcription of the neurogenic gene Delta of Drosophila melanogaster. Haenlin, M., Kramatschek, B., Campos-Ortega, J.A. Development (1990) [Pubmed]
  17. X-Serrate-1 is involved in primary neurogenesis in Xenopus laevis in a complementary manner with X-Delta-1. Kiyota, T., Jono, H., Kuriyama, S., Hasegawa, K., Miyatani, S., Kinoshita, T. Dev. Genes Evol. (2001) [Pubmed]
  18. Both synchronous and asynchronous muscle isoforms of projectin (the Drosophila bent locus product) contain functional kinase domains. Ayme-Southgate, A., Southgate, R., Saide, J., Benian, G.M., Pardue, M.L. J. Cell Biol. (1995) [Pubmed]
  19. latheo, a new gene involved in associative learning and memory in Drosophila melanogaster, identified from P element mutagenesis. Boynton, S., Tully, T. Genetics (1992) [Pubmed]
  20. Ligand-binding and signaling properties of the Ax[M1] form of Notch. Pérez, L., Milán, M., Bray, S., Cohen, S.M. Mech. Dev. (2005) [Pubmed]
  21. Bearded family members inhibit Neuralized-mediated endocytosis and signaling activity of Delta in Drosophila. Bardin, A.J., Schweisguth, F. Dev. Cell (2006) [Pubmed]
  22. An NRSF/REST-like repressor downstream of Ebi/SMRTER/Su(H) regulates eye development in Drosophila. Tsuda, L., Kaido, M., Lim, Y.M., Kato, K., Aigaki, T., Hayashi, S. EMBO J. (2006) [Pubmed]
  23. Molecular basis of intracistronic complementation in the Passover locus of Drosophila. Krishnan, S.N., Frei, E., Schalet, A.P., Wyman, R.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  24. Unidirectional Notch signaling depends on continuous cleavage of Delta. Sapir, A., Assa-Kunik, E., Tsruya, R., Schejter, E., Shilo, B.Z. Development (2005) [Pubmed]
  25. Echinoid mutants exhibit neurogenic phenotypes and show synergistic interactions with the Notch signaling pathway. Ahmed, A., Chandra, S., Magarinos, M., Vaessin, H. Development (2003) [Pubmed]
  26. Interactions among Delta, Serrate and Fringe modulate Notch activity during Drosophila wing development. Klein, T., Arias, A.M. Development (1998) [Pubmed]
  27. Fringe modulates Notch-ligand interactions. Panin, V.M., Papayannopoulos, V., Wilson, R., Irvine, K.D. Nature (1997) [Pubmed]
  28. Notch signalling and the initiation of neural development in the Drosophila eye. Baonza, A., Freeman, M. Development (2001) [Pubmed]
  29. The daughterless gene functions together with Notch and Delta in the control of ovarian follicle development in Drosophila. Cummings, C.A., Cronmiller, C. Development (1994) [Pubmed]
  30. Deciphering synergistic and redundant roles of Hedgehog, Decapentaplegic and Delta that drive the wave of differentiation in Drosophila eye development. Fu, W., Baker, N.E. Development (2003) [Pubmed]
  31. Genetic and molecular characterization of a Notch mutation in its Delta- and Serrate-binding domain in Drosophila. de Celis, J.F., Barrio, R., del Arco, A., García-Bellido, A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  32. The adhesion force of Notch with Delta and the rate of Notch signaling. Ahimou, F., Mok, L.P., Bardot, B., Wesley, C. J. Cell Biol. (2004) [Pubmed]
  33. Edd, the murine hyperplastic disc gene, is essential for yolk sac vascularization and chorioallantoic fusion. Saunders, D.N., Hird, S.L., Withington, S.L., Dunwoodie, S.L., Henderson, M.J., Biben, C., Sutherland, R.L., Ormandy, C.J., Watts, C.K. Mol. Cell. Biol. (2004) [Pubmed]
  34. Molecular analysis of a cellular decision during embryonic development of Drosophila melanogaster: epidermogenesis or neurogenesis. Campos-Ortega, J.A., Knust, E. Eur. J. Biochem. (1990) [Pubmed]
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