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Gene Review

dsh  -  dishevelled

Drosophila melanogaster

Synonyms: CG1720, CG18361, DSH, Dm Dsh, Dmel\CG18361, ...
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Disease relevance of dsh


High impact information on dsh

  • Finally, accumulation of Dishevelled and Inturned near the basal apparatus of cilia suggests that these proteins function in a common pathway with core PCP components to regulate ciliogenesis [2].
  • Planar cell polarity signaling in Drosophila requires the receptor Frizzled and the cytoplasmic proteins Dishevelled and Prickle [3].
  • Rescue analysis reveals different protein domain requirements in Dishevelled for the two pathways; the C-terminal DEP domain is essential to rescue planar polarity defects and induce JNK signaling [4].
  • Here we show that the transmembrane receptor Notch is required downstream of dsh in R3/R4 for them to adopt distinct fates [5].
  • dishevelled and armadillo act in the wingless signalling pathway in Drosophila [6].

Biological context of dsh

  • We conclude that dsh, a highly conserved gene, is not merely a permissive factor in Wg signaling but encodes a novel signal transduction molecule, which may function between the Wg receptor and more downstream signaling molecules [7].
  • Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways [8].
  • Sharp borders of gene expression correlating precisely with clone boundaries suggest that the effects of DSH and SGG on transcription of wg and dpp are not mediated by secreted factors but rather act through intracellular effectors [9].
  • While no functional motifs were identified, one region of Dvl-1 was found to be similar to a domain of discs large-1 (dlg), a Drosophila tumor suppressor gene [10].
  • Throughout postnatal development of the brain Dvl-1 is highly expressed in areas of high neuronal cell density [10].

Anatomical context of dsh


Associations of dsh with chemical compounds


Physical interactions of dsh

  • Yeast two hybrid and in vitro experiments indicate that Nkd directly binds to the basic-PDZ region of Dsh [15].

Co-localisations of dsh

  • A portion of Dsh colocalized with Fmi, and the distributions of both proteins were interdependent [16].

Regulatory relationships of dsh

  • Overexpression of CKIalpha induced hyper-phosphorylation of both Arm and Dishevelled in S2R+ cells and, conversely, CKIalpha-RNAi reduced the amount of hyper-modified forms [17].

Other interactions of dsh


Analytical, diagnostic and therapeutic context of dsh

  • EFX corresponds to a minimal domain required for fly or vertebrate Nkd to interact with the basic/PDZ domains of fly Dsh or vertebrate Dvl proteins in the yeast two-hybrid assay [20].
  • To learn more about how Dsh can discriminate between these functions, we performed genetic screens to isolate additional dsh alleles and we examined the potential role of protein phosphorylation by site-directed mutagenesis [21].
  • Utilizing RT-PCR with degenerate primers, we isolated another member of the mouse Dishevelled (Dvl) gene family, Dvl3 [22].


  1. Up-regulation and overproduction of DVL-1, the human counterpart of the Drosophila dishevelled gene, in cervical squamous cell carcinoma. Okino, K., Nagai, H., Hatta, M., Nagahata, T., Yoneyama, K., Ohta, Y., Jin, E., Kawanami, O., Araki, T., Emi, M. Oncol. Rep. (2003) [Pubmed]
  2. Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling. Park, T.J., Haigo, S.L., Wallingford, J.B. Nat. Genet. (2006) [Pubmed]
  3. Prickle mediates feedback amplification to generate asymmetric planar cell polarity signaling. Tree, D.R., Shulman, J.M., Rousset, R., Scott, M.P., Gubb, D., Axelrod, J.D. Cell (2002) [Pubmed]
  4. Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. Boutros, M., Paricio, N., Strutt, D.I., Mlodzik, M. Cell (1998) [Pubmed]
  5. Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye. Cooper, M.T., Bray, S.J. Nature (1999) [Pubmed]
  6. dishevelled and armadillo act in the wingless signalling pathway in Drosophila. Noordermeer, J., Klingensmith, J., Perrimon, N., Nusse, R. Nature (1994) [Pubmed]
  7. 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]
  8. Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Axelrod, J.D., Miller, J.R., Shulman, J.M., Moon, R.T., Perrimon, N. Genes Dev. (1998) [Pubmed]
  9. Shaggy and dishevelled exert opposite effects on Wingless and Decapentaplegic expression and on positional identity in imaginal discs. Heslip, T.R., Theisen, H., Walker, H., Marsh, J.L. Development (1997) [Pubmed]
  10. Isolation and characterization of a mouse homolog of the Drosophila segment polarity gene dishevelled. Sussman, D.J., Klingensmith, J., Salinas, P., Adams, P.S., Nusse, R., Perrimon, N. Dev. Biol. (1994) [Pubmed]
  11. A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling. Cliffe, A., Hamada, F., Bienz, M. Curr. Biol. (2003) [Pubmed]
  12. Accumulation of Armadillo induced by Wingless, Dishevelled, and dominant-negative Zeste-White 3 leads to elevated DE-cadherin in Drosophila clone 8 wing disc cells. Yanagawa, S., Lee, J.S., Haruna, T., Oda, H., Uemura, T., Takeichi, M., Ishimoto, A. J. Biol. Chem. (1997) [Pubmed]
  13. Internalization is required for proper Wingless signaling in Drosophila melanogaster. Seto, E.S., Bellen, H.J. J. Cell Biol. (2006) [Pubmed]
  14. 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]
  15. Naked cuticle targets dishevelled to antagonize Wnt signal transduction. Rousset, R., Mack, J.A., Wharton, K.A., Axelrod, J.D., Cadigan, K.M., Fish, M.P., Nusse, R., Scott, M.P. Genes Dev. (2001) [Pubmed]
  16. Asymmetric colocalization of Flamingo, a seven-pass transmembrane cadherin, and Dishevelled in planar cell polarization. Shimada, Y., Usui, T., Yanagawa, S., Takeichi, M., Uemura, T. Curr. Biol. (2001) [Pubmed]
  17. Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila. Yanagawa, S., Matsuda, Y., Lee, J.S., Matsubayashi, H., Sese, S., Kadowaki, T., Ishimoto, A. EMBO J. (2002) [Pubmed]
  18. Dishevelled is a component of the frizzled signaling pathway in Drosophila. Krasnow, R.E., Wong, L.L., Adler, P.N. Development (1995) [Pubmed]
  19. Drosophila Twins regulates Armadillo levels in response to Wg/Wnt signal. Bajpai, R., Makhijani, K., Rao, P.R., Shashidhara, L.S. Development (2004) [Pubmed]
  20. 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]
  21. A mutational analysis of dishevelled in Drosophila defines novel domains in the dishevelled protein as well as novel suppressing alleles of axin. Penton, A., Wodarz, A., Nusse, R. Genetics (2002) [Pubmed]
  22. Isolation and characterization of mouse dishevelled-3. Tsang, M., Lijam, N., Yang, Y., Beier, D.R., Wynshaw-Boris, A., Sussman, D.J. Dev. Dyn. (1996) [Pubmed]
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