The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

wg  -  wingless

Drosophila melanogaster

Synonyms: Br, CG4889, DWint-1, DWnt-1, Dint-1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of wg


Psychiatry related information on wg

  • In wg- embryos and in conditional mutants in which wg function is inactivated during a critical period between three and five hours after egg laying, early en expression begins normally but then disappears within several hours [6].

High impact information on wg

  • Here, we describe the discovery of a novel Wnt pathway component, Wntless (Wls/Evi), and show that it is required for Wingless-dependent patterning processes in Drosophila, for MOM-2-governed polarization of blastomeres in C. elegans, and for Wnt3a-mediated communication between cultured human cells [7].
  • Consequently, boca is an essential component of the Wingless pathway but is more generally required for the activities of multiple LDL receptor family members [8].
  • The altered chromatin state is evidenced by ectopic expression of the morphogen wingless in eye imaginal discs and a corresponding abnormal eye phenotype, both of which are epigenetically heritable in subsequent generations, even when function of Hsp90 is restored [9].
  • Boca, an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members in Drosophila [8].
  • Ci-155 proteolysis is also inhibited if cells lack activity of the Drosophila GSK3, Shaggy, previously implicated in Wingless signaling [10].

Biological context of wg


Anatomical context of wg

  • During the late cellular blastoderm stage of Drosophila embryo-genesis the segmentation genes engrailed, en, and wingless, wg, become expressed in two series of 14 stripes which will subsequently coincide with the anterior and posterior limits of each parasegment [15].
  • In addition, abd-A function is required for the expression of wg in the visceral mesoderm posterior to the dpp-expressing cells [16].
  • We show that approximately 4.5 kb immediately upstream of the wg transcription unit can direct expression of the reporter gene lacZ in domains similar to the normal wg pattern in the embryonic ectoderm [17].
  • The Wg signal regulates dve expression during proventriculus development [18].
  • Combgap is thus a tissue-specific relay between Wingless and its target genes for the determination of cell fate in the visual cortex [19].

Associations of wg with chemical compounds


Physical interactions of wg

  • It may permit the subsequent inactivation of the Axin complex by Wingless signaling [25].
  • These findings suggest that a cell-surface proteoglycan is a component of a Wg/Wnt receptor complex [26].
  • Osa-containing Brahma chromatin remodeling complexes are required for the repression of wingless target genes [27].
  • In an extension of these experiments, we tested whether two different subdomains of the Wg protein would by themselves bind to Frizzled and generate a biological response [28].
  • Porc binds the N-terminal 24-amino acid domain (residues 83-106) of Wg, which is highly conserved in the Wnt family and stimulates the N-glycosylation at surrounding sites [24].

Enzymatic interactions of wg

  • In agreement with a previous study using human GSK-3beta, Wg did not cause phosphorylation changes of the Ser9 or Tyr214 regulatory phosphorylated sites of Sgg [29].
  • Notch gain-of-function alleles in which Notch activity is not restricted to the dorsoventral boundary cause miss-expression of cut and wingless and overgrowth of the disc, illustrating the importance of localised Notch activation for wing development [30].
  • Finally, we show that Delta and Serrate play a dual role in the regulation of cut and wingless expression [31].
  • The levels of expression of wingless and cut at the presumptive wing margins were reduced in the late third-instar larvae of hrg mutants [32].

Regulatory relationships of wg

  • The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila [26].
  • Wg signal reception downregulates combgap expression and derepresses target gene transcription [19].
  • Using Drosophila cell line assays, we found, in contrast to previous reports, that Wg induces accumulation of its transducer Armadillo (Arm)/beta-catenin without significant alteration of global Sgg-specific activity [29].
  • In the allocation phase, dll is activated by wg but repressed by dpp [33].
  • The default activity of Ptc is to inhibit Ci function; when Ptc binds Hh, this inhibition is released and Ci can control wg transcription [17].

Other interactions of wg

  • Hh is secreted by posterior cells; it acts at short range to induce dorsal anterior cells to secrete Dpp and ventral anterior cells to secrete Wg [34].
  • Direct Wg autoregulation (autocrine signalling) is masked by its paracrine role in maintaining hh, which in turn maintains wg [35].
  • Loss of function of slimb results in a cell-autonomous accumulation of high levels of both Ci and Arm, and the ectopic expression of both Hh- and Wg- responsive genes [36].
  • We have identified the product of division abnormally delayed (dally), a glycosyl-phosphatidyl inositol (GPI)-linked glypican, as a heparan sulphate proteoglycan molecule involved in Wg signalling [37].
  • Analysis of clones mutant for the Dpp receptors encoded by punt or thickveins (tkv) reveals that repression of wg expression is one critical function of Dpp signalling in leg and wing discs [38].
  • Our findings link Wls and retromer functions in the same conserved Wnt secretion pathway [39].
  • These activities of Trabid are required for efficient TCF-mediated transcription in cells with high Wnt pathway activity, including colorectal cancer cell lines [40].

Analytical, diagnostic and therapeutic context of wg

  • We have recently developed a cell culture system for Wg protein activity, and using this in vitro system as well as intact Drosophila embryos, we have analyzed biochemical changes in the Dsh protein as a consequence of Wg signaling [41].
  • Mutations that affect individual proteoglycans or the enzymes required for glycosaminoglycan synthesis regulate Wingless and Decapentaplegic signaling in Drosophila, and body size in mice and humans [42].
  • We analyzed the expression profiles of cells induced by ectopic Wingless expression to transdetermine from leg to wing by dissecting transdetermined cells and hybridizing probes generated by linear RNA amplification to DNA microarrays [43].
  • Aberrant activation of WNT/PCP signaling pathway in human cancer leads to more malignant phenotypes, such as abnormal tissue polarity, invasion, and metastasis. cDNA-PCR, microarray or ELISA reflecting aberrant activation of WNT/PCP signaling pathway could be developed as novel cancer prognostics [44].
  • In situ hybridization shows that wg is also expressed in the imaginal discs which give rise to the adult during metamorphosis [45].


  1. Mutual antagonism between signals secreted by adjacent wingless and engrailed cells leads to specification of complementary regions of the Drosophila parasegment. Gritzan, U., Hatini, V., DiNardo, S. Development (1999) [Pubmed]
  2. BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires Pygopus for its function in Wg/Wnt signaling. Hoffmans, R., Basler, K. Mech. Dev. (2007) [Pubmed]
  3. Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion. Bradley, R.S., Cowin, P., Brown, A.M. J. Cell Biol. (1993) [Pubmed]
  4. A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23. Wang, Y.K., Samos, C.H., Peoples, R., Pérez-Jurado, L.A., Nusse, R., Francke, U. Hum. Mol. Genet. (1997) [Pubmed]
  5. Drosophila wingless: a paradigm for the function and mechanism of Wnt signaling. Siegfried, E., Perrimon, N. Bioessays (1994) [Pubmed]
  6. Intercellular signalling in Drosophila segment formation reconstructed in vitro. Cumberledge, S., Krasnow, M.A. Nature (1993) [Pubmed]
  7. Wntless, a conserved membrane protein dedicated to the secretion of wnt proteins from signaling cells. Bänziger, C., Soldini, D., Schütt, C., Zipperlen, P., Hausmann, G., Basler, K. Cell (2006) [Pubmed]
  8. Boca, an endoplasmic reticulum protein required for wingless signaling and trafficking of LDL receptor family members in Drosophila. Culi, J., Mann, R.S. Cell (2003) [Pubmed]
  9. Evidence for an epigenetic mechanism by which Hsp90 acts as a capacitor for morphological evolution. Sollars, V., Lu, X., Xiao, L., Wang, X., Garfinkel, M.D., Ruden, D.M. Nat. Genet. (2003) [Pubmed]
  10. Proteolysis of the Hedgehog signaling effector Cubitus interruptus requires phosphorylation by Glycogen Synthase Kinase 3 and Casein Kinase 1. Price, M.A., Kalderon, D. Cell (2002) [Pubmed]
  11. wingless signaling acts through zeste-white 3, the Drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fate. Siegfried, E., Chou, T.B., Perrimon, N. Cell (1992) [Pubmed]
  12. Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning. Lepage, T., Cohen, S.M., Diaz-Benjumea, F.J., Parkhurst, S.M. Nature (1995) [Pubmed]
  13. Components of wingless signalling in Drosophila. Siegfried, E., Wilder, E.L., Perrimon, N. Nature (1994) [Pubmed]
  14. Requirement for Pangolin/dTCF in Drosophila Wingless signaling. Schweizer, L., Nellen, D., Basler, K. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  15. Regulation of segment polarity genes in the Drosophila blastoderm by fushi tarazu and even skipped. Ingham, P.W., Baker, N.E., Martinez-Arias, A. Nature (1988) [Pubmed]
  16. Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos. Reuter, R., Panganiban, G.E., Hoffmann, F.M., Scott, M.P. Development (1990) [Pubmed]
  17. Expression of wingless in the Drosophila embryo: a conserved cis-acting element lacking conserved Ci-binding sites is required for patched-mediated repression. Lessing, D., Nusse, R. Development (1998) [Pubmed]
  18. A novel homeobox gene mediates the Dpp signal to establish functional specificity within target cells. Nakagoshi, H., Hoshi, M., Nabeshima, Y., Matsuzaki, F. Genes Dev. (1998) [Pubmed]
  19. Combgap relays wingless signal reception to the determination of cortical cell fate in the Drosophila visual system. Song, Y., Chung, S., Kunes, S. Mol. Cell (2000) [Pubmed]
  20. Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C. Cook, D., Fry, M.J., Hughes, K., Sumathipala, R., Woodgett, J.R., Dale, T.C. EMBO J. (1996) [Pubmed]
  21. Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila. Haerry, T.E., Heslip, T.R., Marsh, J.L., O'Connor, M.B. Development (1997) [Pubmed]
  22. Regulation of the protein kinase activity of Shaggy(Zeste-white3) by components of the wingless pathway in Drosophila cells and embryos. Ruel, L., Stambolic, V., Ali, A., Manoukian, A.S., Woodgett, J.R. J. Biol. Chem. (1999) [Pubmed]
  23. Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Stambolic, V., Ruel, L., Woodgett, J.R. Curr. Biol. (1996) [Pubmed]
  24. Drosophila segment polarity gene product porcupine stimulates the posttranslational N-glycosylation of wingless in the endoplasmic reticulum. Tanaka, K., Kitagawa, Y., Kadowaki, T. J. Biol. Chem. (2002) [Pubmed]
  25. A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling. Cliffe, A., Hamada, F., Bienz, M. Curr. Biol. (2003) [Pubmed]
  26. The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila. Tsuda, M., Kamimura, K., Nakato, H., Archer, M., Staatz, W., Fox, B., Humphrey, M., Olson, S., Futch, T., Kaluza, V., Siegfried, E., Stam, L., Selleck, S.B. Nature (1999) [Pubmed]
  27. Osa-containing Brahma chromatin remodeling complexes are required for the repression of wingless target genes. Collins, R.T., Treisman, J.E. Genes Dev. (2000) [Pubmed]
  28. Ligand receptor interactions in the Wnt signaling pathway in Drosophila. Wu, C.H., Nusse, R. J. Biol. Chem. (2002) [Pubmed]
  29. Functional studies of shaggy/glycogen synthase kinase 3 phosphorylation sites in Drosophila melanogaster. Papadopoulou, D., Bianchi, M.W., Bourouis, M. Mol. Cell. Biol. (2004) [Pubmed]
  30. Activation and function of Notch at the dorsal-ventral boundary of the wing imaginal disc. de Celis, J.F., Garcia-Bellido, A., Bray, S.J. Development (1996) [Pubmed]
  31. The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless and a dominant negative role for Delta and Serrate. Micchelli, C.A., Rulifson, E.J., Blair, S.S. Development (1997) [Pubmed]
  32. The hiiragi gene encodes a poly(A) polymerase, which controls the formation of the wing margin in Drosophila melanogaster. Murata, T., Nagaso, H., Kashiwabara , S., Baba, T., Okano, H., Yokoyama, K.K. Dev. Biol. (2001) [Pubmed]
  33. Leg development in flies versus grasshoppers: differences in dpp expression do not lead to differences in the expression of downstream components of the leg patterning pathway. Jockusch, E.L., Nulsen, C., Newfeld, S.J., Nagy, L.M. Development (2000) [Pubmed]
  34. Complementary and mutually exclusive activities of decapentaplegic and wingless organize axial patterning during Drosophila leg development. Jiang, J., Struhl, G. Cell (1996) [Pubmed]
  35. Distinct pathways for autocrine and paracrine Wingless signalling in Drosophila embryos. Hooper, J.E. Nature (1994) [Pubmed]
  36. Regulation of the Hedgehog and Wingless signalling pathways by the F-box/WD40-repeat protein Slimb. Jiang, J., Struhl, G. Nature (1998) [Pubmed]
  37. Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Lin, X., Perrimon, N. Nature (1999) [Pubmed]
  38. Decapentaplegic restricts the domain of wingless during Drosophila limb patterning. Penton, A., Hoffmann, F.M. Nature (1996) [Pubmed]
  39. The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network. Belenkaya, T.Y., Wu, Y., Tang, X., Zhou, B., Cheng, L., Sharma, Y.V., Yan, D., Selva, E.M., Lin, X. Dev. Cell (2008) [Pubmed]
  40. Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains. Tran, H., Hamada, F., Schwarz-Romond, T., Bienz, M. Genes Dev. (2008) [Pubmed]
  41. The dishevelled protein is modified by wingless signaling in Drosophila. Yanagawa, S., van Leeuwen, F., Wodarz, A., Klingensmith, J., Nusse, R. Genes Dev. (1995) [Pubmed]
  42. Proteoglycans and pattern formation: sugar biochemistry meets developmental genetics. Selleck, S.B. Trends Genet. (2000) [Pubmed]
  43. Regulation of cellular plasticity in Drosophila imaginal disc cells by the Polycomb group, trithorax group and lama genes. Klebes, A., Sustar, A., Kechris, K., Li, H., Schubiger, G., Kornberg, T.B. Development (2005) [Pubmed]
  44. WNT/PCP signaling pathway and human cancer (review). Katoh, M. Oncol. Rep. (2005) [Pubmed]
  45. Transcription of the segment-polarity gene wingless in the imaginal discs of Drosophila, and the phenotype of a pupal-lethal wg mutation. Baker, N.E. Development (1988) [Pubmed]
WikiGenes - Universities