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Gene Review

Wnt5  -  Wnt oncogene analog 5

Drosophila melanogaster

Synonyms: CG6407, DWnt-3, DWnt-3/5, DWnt-5, DWnt3, ...
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Disease relevance of Wnt5


Psychiatry related information on Wnt5


High impact information on Wnt5

  • The Wnt pathway controls cell fates, tissue homeostasis, and cancer [7].
  • 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 [8].
  • We show that EEL can be used to identify Hh and Wnt target genes and to predict activated TFs based on changes in gene expression [9].
  • The Drosophila Wnt, wingless, provides an essential signal for pre- and postsynaptic differentiation [10].
  • Here, we present findings, which challenge this view and suggest instead that beta-catenin may transduce Wnt signals by exporting TCF from the nucleus or activating it in the cytoplasm [11].

Chemical compound and disease context of Wnt5

  • Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway [12].

Biological context of Wnt5

  • These results indicate that, during zebrafish gastrulation Pk1 acts, in part, through interaction with the noncanonical Wnt11/Wnt5 pathway to regulate convergent extension cell movements, but is unlikely to simply be a linear component of this pathway [13].
  • We test each one of the seven DWnts in several ways and find evidence that wg and DWnt2 can function in the developing trachea: when both genes are removed together, the phenotype is identical or very similar to that observed when the Wnt pathway is shut down [14].
  • The expression patterns of these two Wnt/wg homologues are dynamic during Drosophila embryogenesis [15].
  • DWnt-2 and DWnt-3 map to chromosome 2 position 45E and chromosome X position 17A/B, respectively [15].
  • In addition to the Frizzleds, members of the LRP family (represented by the arrow gene in Drosophila) are also necessary for Wnt signal transduction and have been postulated to act as co-receptors [16].

Anatomical context of Wnt5

  • The wg gene helps to pattern the developing trachea but is not responsible for all Wnt functions there [14].
  • Porc is also necessary for the processing of Drosophila Wnt-3/5 in both embryos and cultured cells [17].
  • In addition, Wnt signal activation in the central retina was sufficient to induce the expression of markers of the ciliary body and iris, two tissues derived from the peripheral optic cup (OC) [18].
  • Alteration of matrix glycosaminoglycans diminishes articular chondrocytes' response to a canonical Wnt signal [5].
  • Conditioned media from a cell line that is stably transfected with Wnt3a was used as a source of Wnt protein that activates the canonical signaling pathway [5].

Associations of Wnt5 with chemical compounds

  • The putative translation product of DWnt-2 and the carboxy-terminal half of the deduced DWnt-3 product are both rich in conserved cysteine residues [15].
  • We show that Wnt5, a member of the conserved Wnt secreted glycoprotein family, is required for the formation of the anterior of the two midline-crossing commissures present in each Drosophila hemisegment [1].
  • CONCLUSION: This study demonstrates that articular chondrocytes respond to canonical Wnt stimulation, and that reduced sulfation or CS content diminishes that response [5].
  • By contrast, analysis of bromodeoxyuridine incorporation and transcription of various cardiogenetic markers showed Wnt to have little or no impact on cell proliferation or differentiation [19].
  • In Drosophila, the protein encoded by the Wnt family gene, wingless, signals through a pathway that antagonizes the effects of the serine/threonine kinase zeste-white 3/shaggy [20].

Physical interactions of Wnt5

  • These findings suggest that a cell-surface proteoglycan is a component of a Wg/Wnt receptor complex [21].

Regulatory relationships of Wnt5

  • We show that coexpression of WNT5 and Derailed has no apparent effect upon TCF/LEF-dependent transcription, suggesting that the WNT5/Derailed signaling pathway is unlikely to directly regulate canonical Wnt pathway targets [22].

Other interactions of Wnt5

  • We also show that DWnt-3 does not functionally replace wg in an in vivo assay [23].
  • Here we show that Derailed keeps these axons out of the posterior commissure by acting as a receptor for Wnt5, a member of the Wnt family of secreted signalling molecules [24].
  • The data suggest that the vertebrate Nkd-related proteins, similar to their fly counterpart, may act as inducible antagonists of Wnt signals [25].
  • In Drosophila, wingless and DWnt-4 are two physically clustered Wnt genes, which are transcribed in overlapping patterns during embryogenesis and, in several instances, are controlled by the same regulatory molecules [26].
  • Zinc-dependent interaction between dishevelled and the Drosophila Wnt antagonist naked cuticle [27].

Analytical, diagnostic and therapeutic context of Wnt5

  • Recent work in cell culture has suggested that phosphorylation of Dsh by Casein Kinase I epsilon (CKIepsilon) may act as a molecular "switch," promoting Wnt/beta-catenin while inhibiting Fz/PCP signaling [28].
  • APC is known to down regulate beta-catenin levels, a transducer of Wnt signaling [29].


  1. The Drosophila Wnt5 protein mediates selective axon fasciculation in the embryonic central nervous system. Fradkin, L.G., van Schie, M., Wouda, R.R., de Jong, A., Kamphorst, J.T., Radjkoemar-Bansraj, M., Noordermeer, J.N. Dev. Biol. (2004) [Pubmed]
  2. An unconventional nuclear localization motif is crucial for function of the Drosophila wnt/wingless antagonist naked cuticle. Waldrop, S., Chan, C.C., Cagatay, T., Zhang, S., Rousset, R., Mack, J., Zeng, W., Fish, M., Zhang, M., Amanai, M., Wharton, K.A. Genetics (2006) [Pubmed]
  3. Drosophila wingless: a paradigm for the function and mechanism of Wnt signaling. Siegfried, E., Perrimon, N. Bioessays (1994) [Pubmed]
  4. 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]
  5. Alteration of matrix glycosaminoglycans diminishes articular chondrocytes' response to a canonical Wnt signal. Shortkroff, S., Yates, K.E. Osteoarthr. Cartil. (2007) [Pubmed]
  6. The Wnt-dependent signaling pathways as target in oncology drug discovery. Janssens, N., Janicot, M., Perera, T. Investigational new drugs. (2006) [Pubmed]
  7. Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo. Mosimann, C., Hausmann, G., Basler, K. Cell (2006) [Pubmed]
  8. 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]
  9. Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity. Hallikas, O., Palin, K., Sinjushina, N., Rautiainen, R., Partanen, J., Ukkonen, E., Taipale, J. Cell (2006) [Pubmed]
  10. The Drosophila Wnt, wingless, provides an essential signal for pre- and postsynaptic differentiation. Packard, M., Koo, E.S., Gorczyca, M., Sharpe, J., Cumberledge, S., Budnik, V. Cell (2002) [Pubmed]
  11. Evidence that Armadillo transduces wingless by mediating nuclear export or cytosolic activation of Pangolin. Chan, S.K., Struhl, G. Cell (2002) [Pubmed]
  12. Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway. Berger, Z., Ttofi, E.K., Michel, C.H., Pasco, M.Y., Tenant, S., Rubinsztein, D.C., O'Kane, C.J. Hum. Mol. Genet. (2005) [Pubmed]
  13. Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish. Carreira-Barbosa, F., Concha, M.L., Takeuchi, M., Ueno, N., Wilson, S.W., Tada, M. Development (2003) [Pubmed]
  14. Seven Wnt homologues in Drosophila: a case study of the developing tracheae. Llimargas, M., Lawrence, P.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  15. Isolation and expression of two novel Wnt/wingless gene homologues in Drosophila. Russell, J., Gennissen, A., Nusse, R. Development (1992) [Pubmed]
  16. Ligand receptor interactions in the Wnt signaling pathway in Drosophila. Wu, C.H., Nusse, R. J. Biol. Chem. (2002) [Pubmed]
  17. 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]
  18. Wnt2b/{beta}-catenin-mediated canonical Wnt signaling determines the peripheral fates of the chick eye. Cho, S.H., Cepko, C.L. Development (2006) [Pubmed]
  19. Wnt/frizzled-2 signaling induces aggregation and adhesion among cardiac myocytes by increased cadherin-beta-catenin complex. Toyofuku, T., Hong, Z., Kuzuya, T., Tada, M., Hori, M. J. Cell Biol. (2000) [Pubmed]
  20. Regulation of Spemann organizer formation by the intracellular kinase Xgsk-3. Pierce, S.B., Kimelman, D. Development (1995) [Pubmed]
  21. 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]
  22. Src family kinases are required for WNT5 signaling through the Derailed/RYK receptor in the Drosophila embryonic central nervous system. Wouda, R.R., Bansraj, M.R., de Jong, A.W., Noordermeer, J.N., Fradkin, L.G. Development (2008) [Pubmed]
  23. The Drosophila Wnt protein DWnt-3 is a secreted glycoprotein localized on the axon tracts of the embryonic CNS. Fradkin, L.G., Noordermeer, J.N., Nusse, R. Dev. Biol. (1995) [Pubmed]
  24. Wnt-mediated axon guidance via the Drosophila Derailed receptor. Yoshikawa, S., McKinnon, R.D., Kokel, M., Thomas, J.B. Nature (2003) [Pubmed]
  25. Vertebrate proteins related to Drosophila Naked Cuticle bind Dishevelled and antagonize Wnt signaling. Wharton, K.A., Zimmermann, G., Rousset, R., Scott, M.P. Dev. Biol. (2001) [Pubmed]
  26. Antagonist activity of DWnt-4 and wingless in the Drosophila embryonic ventral ectoderm and in heterologous Xenopus assays. Gieseler, K., Graba, Y., Mariol, M.C., Wilder, E.L., Martinez-Arias, A., Lemaire, P., Pradel, J. Mech. Dev. (1999) [Pubmed]
  27. Zinc-dependent interaction between dishevelled and the Drosophila Wnt antagonist naked cuticle. Rousset, R., Wharton, K.A., Zimmermann, G., Scott, M.P. J. Biol. Chem. (2002) [Pubmed]
  28. CKIepsilon/discs overgrown promotes both Wnt-Fz/beta-catenin and Fz/PCP signaling in Drosophila. Klein, T.J., Jenny, A., Djiane, A., Mlodzik, M. Curr. Biol. (2006) [Pubmed]
  29. Studies on human colon cancer gene APC by targeted expression in Drosophila. Bhandari, P., Shashidhara, L.S. Oncogene (2001) [Pubmed]
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