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Flying at the head of the pack: Wnt biology in Drosophila

Oncogene volume 25, pages 7442–7449 (2006)Cite this article

Abstract

The fruitfly, Drosophila melanogaster, has been of central importance in analysing the mechanics of cellular processes. Classic forward genetic screens in the fly have identified many of the genes that define critical cell signaling pathways, for example. Our understanding of the Wnt pathway, in particular, has benefited from the many advantages that the fly offers as a model system. Here, I review the history of these discoveries and highlight the utility of the fly in dissecting the molecular workings of Wnt signal transduction.

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References

  • Adler PN . (2002). Planar signaling and morphogenesis in Drosophila. Dev Cell 2: 525–535.

    Article  CAS  Google Scholar 

  • Adler PN, Lee H . (2001). Frizzled signaling and cell-cell interactions in planar polarity. Curr Opin Cell Biol 13: 635–640.

    Article  CAS  Google Scholar 

  • Ahmed Y, Hayashi S, Levine A, Wieschaus E . (1998). Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development. Cell 93: 1171–1182.

    Article  CAS  Google Scholar 

  • Babu P . (1977). Early developmental subdivisions of the wing disk in Drosophila. Mol Gen Genet 151: 289–294.

    Article  CAS  Google Scholar 

  • Baker NE . (1987). Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos. EMBO J 6: 1765–1773.

    Article  CAS  Google Scholar 

  • Banziger C, Soldini D, Schutt C, Zipperlen P, Hausmann G, Basler K . (2006). Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell 125: 509–522.

    Article  CAS  Google Scholar 

  • Bartscherer K, Pelte N, Ingelfinger D, Boutros M . (2006). Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 125: 523–533.

    Article  CAS  Google Scholar 

  • Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R et al. (1996). Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 382: 638–642.

    Article  CAS  Google Scholar 

  • Bejsovec A, Wieschaus E . (1993). Segment polarity gene interactions modulate epidermal patterning in Drosophila embryos. Development 119: 501–517.

    CAS  PubMed  Google Scholar 

  • Bejsovec A, Wieschaus E . (1995). Signaling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface. Genetics 139: 309–320.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Belenkaya TY, Han C, Standley HJ, Lin X, Houston DW, Heasman J . (2002). pygopus Encodes a nuclear protein essential for wingless/Wnt signaling. Development 129: 4089–4101.

    CAS  PubMed  Google Scholar 

  • Bhanot P, Brink M, Samos CH, Hsieh JC, Wang Y, Macke JP et al. (1996). A new member of the frizzled family from Drosophila functions as a Wingless receptor. Nature 382: 225–230.

    Article  CAS  Google Scholar 

  • Bhanot P, Fish M, Jemison JA, Nusse R, Nathans J, Cadigan KM . (1999). Frizzled and Dfrizzled-2 function as redundant receptors for Wingless during Drosophila embryonic development. Development 126: 4175–4186.

    CAS  PubMed  Google Scholar 

  • Bienz M, Clevers H . (2000). Linking colorectal cancer to Wnt signaling. Cell 103: 311–320.

    Article  CAS  Google Scholar 

  • Brunner E, Brunner D, Fu W, Hafen E, Basler K . (1999). The dominant mutation Glazed is a gain-of-function allele of wingless that, similar to loss of APC, interferes with normal eye development. Dev Biol 206: 178–188.

    Article  CAS  Google Scholar 

  • Brunner E, Peter O, Schweizer L, Basler K . (1997). pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila. Nature 385: 829–833.

    Article  CAS  Google Scholar 

  • Cavallo RA, Cox RT, Moline MM, Roose J, Polevoy GA, Clevers H et al. (1998). Drosophila Tcf and Groucho interact to repress Wingless signalling activity. Nature 395: 604–608.

    Article  CAS  Google Scholar 

  • Cliffe A, Hamada F, Bienz M . (2003). A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling. Curr Biol 13: 960–966.

    Article  CAS  Google Scholar 

  • Cong F, Schweizer L, Varmus H . (2004). Wnt signals across the plasma membrane to activate the β-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP. Development 131: 5103–5115.

    Article  CAS  Google Scholar 

  • Daniels DL, Weis WI . (2005). Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation. Nat Struct Mol Biol 12: 364–371.

    Article  CAS  Google Scholar 

  • DasGupta R, Kaykas A, Moon RT, Perrimon N . (2005). Functional genomic analysis of the Wnt-wingless signaling pathway. Science 308: 826–833.

    Article  CAS  Google Scholar 

  • Dierick HA, Bejsovec A . (1998). Functional analysis of Wingless reveals a link between intercellular ligand transport and dorsal-cell-specific signaling. Development 125: 4729–4738.

    CAS  PubMed  Google Scholar 

  • Hamada F, Tomoyasu Y, Takatsu Y, Nakamura M, Nagai S, Suzuki A et al. (1999). Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin. Science 283: 1739–1742.

    Article  CAS  Google Scholar 

  • Immergluck K, Lawrence PA, Bienz M . (1990). Induction across germ layers in Drosophila mediated by a genetic cascade. Cell 62: 261–268.

    Article  CAS  Google Scholar 

  • Jones WM, Bejsovec A . (2005). RacGap50C negatively regulates wingless pathway activity during Drosophila embryonic development. Genetics 169: 2075–2086.

    Article  CAS  Google Scholar 

  • Jürgens G, Wieschaus E, Nüsslein-Volhard C, Kluding H . (1984). Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster: II. Zygotic loci on the third chromosome. Wilhelm Roux's Arch Dev Biol 193: 283–295.

    Article  Google Scholar 

  • Korinek V, Barker N, Morin PJ, van Wichen D, de Weger R, Kinzler KW et al. (1997). Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC(−/−) colon carcinoma. Science 275: 1784–1787.

    Article  CAS  Google Scholar 

  • Kramps T, Peter O, Brunner E, Nellen D, Froesch B, Chatterjee S et al. (2002). Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell 109: 47–60.

    Article  CAS  Google Scholar 

  • Lawrence PA, Bodmer R, Vincent JP . (1995). Segmental patterning of heart precursors in Drosophila. Development 121: 4303–4308.

    CAS  PubMed  Google Scholar 

  • Logan CY, Nusse R . (2004). The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20: 781–810.

    Article  CAS  Google Scholar 

  • Mao J, Wang J, Liu B, Pan W, Farr III G, Flynn C et al. (2001). Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell 7: 801–809.

    Article  CAS  Google Scholar 

  • McCartney BM, Dierick HA, Kirkpatrick C, Moline MM, Baas A, Peifer M et al. (1999). Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis. J Cell Biol 146: 1303–1318.

    Article  CAS  Google Scholar 

  • McCartney BM, Price MH, Webb RL, Hayden MA, Holot LM, Zhou M et al. (2006). Testing hypotheses for the functions of APC family proteins using null and truncation alleles in Drosophila. Development 133: 2407–2418.

    Article  CAS  Google Scholar 

  • Molenaar M, van de Wetering M, Oosterwegel M, Petersonmaduro J, Godsave S, Korinek V et al. (1996). XTcf-3 transcription factor mediates beta-catenin induced axis formation in Xenopus embryos. Cell 86: 391–399.

    Article  CAS  Google Scholar 

  • Moline MM, Dierick HA, Southern C, Bejsovec A . (2000). Non-equivalent roles of Drosophila Frizzled and Dfrizzled2 in embryonic wingless signal transduction. Curr Biol 10: 1127–1130.

    Article  CAS  Google Scholar 

  • Morata G, Lawrence PA . (1977). The development of wingless, a homeotic mutation of Drosophila. Dev Biol 56: 227–240.

    Article  CAS  Google Scholar 

  • Morgan TH, Bridges CB, Schultz J . (1936). Constitution of the germinal material in relation to heredity. Year Book of the Carnegie Institution of Washington 35: 289–297.

    Google Scholar 

  • Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B et al. (1997). Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275: 1787–1790.

    Article  CAS  Google Scholar 

  • Muller H, Samanta R, Wieschaus E . (1999). Wingless signaling in the Drosophila embryo: zygotic requirements and the role of the frizzled genes. Development 126: 577–586.

    CAS  PubMed  Google Scholar 

  • Noordermeer J, Johnston P, Rijsewijk F, Nusse R, Lawrence PA . (1992). The consequences of ubiquitous expression of the wingless gene in the Drosophila embryo. Development 116: 711–719.

    CAS  PubMed  Google Scholar 

  • Noordermeer J, Klingensmith J, Perrimon N, Nusse R . (1994). Dishevelled and armadillo act in the wingless signalling pathway in Drosophila. Nature 367: 80–83.

    Article  CAS  Google Scholar 

  • Nusse R, van Ooyen A, Cox D, Fung YK, Varmus H . (1984). Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature 307: 131–136.

    Article  CAS  Google Scholar 

  • Nusse R, Varmus HE . (1982). Many tumors induced by the Mouse Mammary Tumor Virus contain a provirus integrated in the same region of the host genome. Cell 31: 99–109.

    Article  CAS  Google Scholar 

  • Nüsslein-Volhard C, Wieschaus E, Kluding H . (1984). Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster: I. Zygotic loci on the second chromosome. Wilhelm Roux's Arch Dev Biol 193: 267–282.

    Article  Google Scholar 

  • Nüsslein-Volhard C, Wieschaus E . (1980). Mutations affecting segment number and polarity in Drosophila. Nature 287: 795–801.

    Article  Google Scholar 

  • Pai LM, Orsulic S, Bejsovec A, Peifer M . (1997). Negative regulation of Armadillo, a Wingless effector in Drosophila. Development 124: 2255–2266.

    CAS  PubMed  Google Scholar 

  • Parker DS, Jemison J, Cadigan KM . (2002). Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development 129: 2565–2576.

    CAS  PubMed  Google Scholar 

  • Patel NH, Schafer B, Goodman CS, Holmgren R . (1989). The role of segment polarity genes during Drosophila neurogenesis. Genes Dev 3: 890–904.

    Article  CAS  Google Scholar 

  • Peifer M, Pai LM, Casey M . (1994a). Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for wingless signal and zeste-white 3 kinase. Dev Biol 166: 543–556.

    Article  CAS  Google Scholar 

  • Peifer M, Sweeton D, Casey M, Wieschaus E . (1994b). wingless signal and Zeste-white 3 kinase trigger opposing changes in the intracellular distribution of Armadillo. Development 120: 369–380.

    CAS  PubMed  Google Scholar 

  • Peifer M, Wieschaus E . (1990). The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell 63: 1167–1178.

    Article  CAS  Google Scholar 

  • Perrimon N, Engstrom L, Mahowald AP . (1989). Zygotic lethals with specific maternal effect phenotypes in Drosophila melanogaster. I. Loci on the X chromosome. Genetics 121: 333–352.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Perrimon N, Gans M . (1983). Clonal analysis of the tissue specificity of recessive female-sterile mutations of Drosophila melanogaster using a dominant female-sterile mutation Fs(1)K1237. Dev Biol 100: 365–373.

    Article  CAS  Google Scholar 

  • Polakis P . (2000). Wnt signaling and cancer. Genes Dev 14: 1837–1851.

    CAS  PubMed  Google Scholar 

  • Riese J, Yu X, Munnerlyn A, Eresh S, Hsu SC, Grosschedl R et al. (1997). LEF-1, a nuclear factor coordinating signaling inputs from wingless and decapentaplegic. Cell 88: 777–787.

    Article  CAS  Google Scholar 

  • Riggleman B, Schedl P, Wieschaus E . (1990). Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless. Cell 63: 549–560.

    Article  CAS  Google Scholar 

  • Riggleman B, Wieschaus E, Schedl P . (1989). Molecular analysis of the armadillo locus: uniformly distributed transcripts and a protein with novel internal repeats are associated with a Drosophila segment polarity gene. Genes Dev 3: 96–113.

    Article  CAS  Google Scholar 

  • Rijsewijk F, Schuermann M, Wagenaar E, Parren P, Weigel D, Nusse R . (1987). The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell 50: 649–657.

    Article  CAS  Google Scholar 

  • Rubinfeld B, Robbins P, ElGamil M, Albert I, Porfiri E, Polakis P . (1997). Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 275: 1790–1792.

    Article  CAS  Google Scholar 

  • Rulifson EJ, Wu CH, Nusse R . (2000). Pathway specificity by the bifunctional receptor frizzled is determined by affinity for wingless. Mol Cell 6: 117–126.

    Article  CAS  Google Scholar 

  • Sharma RP, Chopra VL . (1976). Effect of the Wingless (wg1) mutation on wing and haltere development in Drosophila melanogaster. Dev Biol 48: 461–465.

    Article  CAS  Google Scholar 

  • Siegfried E, Wilder EL, Perrimon N . (1994). Components of wingless signalling in Drosophila. Nature 367: 76–80.

    Article  CAS  Google Scholar 

  • Smits R, Hofland N, Edelmann W, Geugien M, Jagmohan-Changur S, Albuquerque C et al. (2000). Somatic Apc mutations are selected upon their capacity to inactivate the beta-catenin downregulating activity. Genes Chromosomes Cancer 29: 229–239.

    Article  CAS  Google Scholar 

  • Smits R, van der Houven van Oordt W, Luz A, Zurcher C, Jagmohan-Changur S, Breukel C et al. (1998). Apc1638N: a mouse model for familial adenomatous polyposis-associated desmoid tumors and cutaneous cysts. Gastroenterology 114: 275–283.

    Article  CAS  Google Scholar 

  • Thompson B, Townsley F, Rosin-Arbesfeld R, Musisi H, Bienz M . (2002). A new nuclear component of the Wnt signalling pathway. Nat Cell Biol 4: 367–373.

    Article  CAS  Google Scholar 

  • Tolwinski NS, Wehrli M, Rives A, Erdeniz N, DiNardo S, Wieschaus E . (2003). Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity. Dev Cell 4: 407–418.

    Article  CAS  Google Scholar 

  • van de Wetering M, Cavallo R, Dooijes D, van Beest M, van Es J, Loureiro J et al. (1997). Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF. Cell 88: 789–799.

    Article  CAS  Google Scholar 

  • van den Heuvel M, Harryman-Samos C, Klingensmith J, Perrimon N, Nusse R . (1993). Mutations in the segment polarity genes wingless and porcupine impair secretion of the wingless protein. EMBO J 12: 5293–5302.

    Article  CAS  Google Scholar 

  • van Leeuwen F, Samos CH, Nusse R . (1994). Biological activity of soluble wingless protein in cultured Drosophila imaginal disc cells. Nature 368: 342–344.

    Article  CAS  Google Scholar 

  • Wehrli M, Dougan ST, Caldwell K, O'Keefe L, Schwartz S, Vaizel-Ohayon D et al. (2000). Arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature 407: 527–530.

    Article  CAS  Google Scholar 

  • Wieschaus E, Nüsslein-Volhard C, Jurgens G . (1984). Mutations affecting the pattern of the larval cuticle in Drosophila melanogaster: zygotic loci on the X-chromosome and the fourth chromosome. Wilhelm Roux's Arch Dev Biol 193: 296–307.

    Article  CAS  Google Scholar 

  • Willert K, Brown JD, Danenberg E, Duncan AW, Weissman IL, Reya T et al. (2003). Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423: 448–452.

    Article  CAS  Google Scholar 

  • Willert K, Logan CY, Arora A, Fish M, Nusse R . (1999). A Drosophila Axin homolog, Daxin, inhibits Wnt signaling. Development 126: 4165–4173.

    CAS  PubMed  Google Scholar 

  • Wong HC, Bourdelas A, Krauss A, Lee HJ, Shao Y, Wu D et al. (2003). Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled. Mol Cell 12: 1251–1260.

    Article  CAS  Google Scholar 

  • Wu CH, Nusse R . (2002). Ligand receptor interactions in the Wnt signaling pathway in Drosophila. J Biol Chem 277: 41762–41769.

    Article  CAS  Google Scholar 

  • Yu X, Waltzer L, Bienz M . (1999). A new Drosophila APC homologue associated with adhesive zones of epithelial cells. Nat Cell Biol 1: 144–151.

    Article  CAS  Google Scholar 

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Acknowledgements

The author is very grateful to E Wieschaus and M Peifer for corrections, encouragement, and comments on the paper. The author's work is supported by the National Science Foundation.

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    A Bejsovec

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Bejsovec, A. Flying at the head of the pack: Wnt biology in Drosophila. Oncogene 25, 7442–7449 (2006). https://doi.org/10.1038/sj.onc.1210051

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