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Gene Review

Wnt2  -  Wnt oncogene analog 2

Drosophila melanogaster

Synonyms: CG1916, D-wnt-2, DWnt-2, DWnt2, Dm DWnt2, ...
 
 
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Disease relevance of Wnt2

 

Psychiatry related information on Wnt2

 

High impact information on Wnt2

  • We report here that DWnt-2, a secreted glycoprotein related to wingless, is a signal required for cell fate determination and morphogenesis in the developing male reproductive tract [6].
  • DWnt-2 is expressed in somatic cells of the gonad throughout development, implicating it as a signal that can influence pigment cell fate directly [6].
  • Testes from DWnt-2 null mutant flies lack the male-specific pigment cells of the reproductive tract sheath and the muscle precursors of the sheath fail to migrate normally [6].
  • The Wnt/beta-catenin signaling pathway is critical in both cellular proliferation and organismal development [7].
  • Diversin also affects planar cell polarity in Drosophila, which is controlled by the noncanonical Wnt signaling pathway [8].
 

Biological context of Wnt2

  • Wnt ligands have pleiotropic and context-specific roles in embryogenesis and adult tissues [9].
  • DWnt-2 and DWnt-3 map to chromosome 2 position 45E and chromosome X position 17A/B, respectively [10].
  • 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 [11].
  • The amenability of Drosophila for genetic manipulation and analysis of ocular phenotypes has delivered a great deal of information about the roles of the Wnt/Fzd signaling pathways at various stages of ocular development and growth, particularly in regulating the formation and size of the eye field, cell proliferation, polarity and differentiation [12].
  • Developmental stage-specific biphasic roles of Wnt/beta-catenin signaling in cardiomyogenesis and hematopoiesis [13].
 

Anatomical context of Wnt2

  • The distribution of DWnt-2 transcripts is predominantly segmented, with the additional presence of transcripts in the presumptive gonads [10].
  • DWnt-2 is expressed in the epithelium of the wing hinge primordium during pupation [14].
  • Although the expression pattern of DWnt-2 suggests that it could influence epithelial cells to differentiate into attachment sites for muscle, the expression of stripe, a transcription factor necessary for epithelial cells to adopt an attachment cell fate, is unaltered in the mutant [14].
  • As the LG4-LG5 domain of the alpha4 chain is cleaved in vivo from the main body of laminin-8 (alpha4beta1gamma1), we suggest that the heparan sulphate proteoglycan-binding activity of LG4 is significant in modulating the signalling of Wnt, Decapentaplegic and fibroblast growth factors [15].
  • Our murine model provides a useful platform to study human MDS/AML transformation, as well as the Wnt/beta-catenin pathway's role in the pathogenesis of leukemia stem cells [16].
 

Associations of Wnt2 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 [10].
  • CONCLUSION: This study demonstrates that articular chondrocytes respond to canonical Wnt stimulation, and that reduced sulfation or CS content diminishes that response [3].
 

Other interactions of Wnt2

  • We find that the seven DWnt genes vary in their effectiveness in specific tissues, such as the tracheae, and, moreover, the epidermis and the tracheae respond to DWnt2 and Wg differently [17].
  • We show that this process is largely dependent on Sox9 function as Wnt-mediated neural crest induction is inhibited in the context of Sox9-depleted embryos [18].

References

  1. Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia. Weerkamp, F., van Dongen, J.J., Staal, F.J. Leukemia (2006) [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. Alteration of matrix glycosaminoglycans diminishes articular chondrocytes' response to a canonical Wnt signal. Shortkroff, S., Yates, K.E. Osteoarthr. Cartil. (2007) [Pubmed]
  4. 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]
  5. The Wnt-dependent signaling pathways as target in oncology drug discovery. Janssens, N., Janicot, M., Perera, T. Investigational new drugs. (2006) [Pubmed]
  6. DWnt-2, a Drosophila Wnt gene required for the development of the male reproductive tract, specifies a sexually dimorphic cell fate. Kozopas, K.M., Samos, C.H., Nusse, R. Genes Dev. (1998) [Pubmed]
  7. Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex. Luo, W., Peterson, A., Garcia, B.A., Coombs, G., Kofahl, B., Heinrich, R., Shabanowitz, J., Hunt, D.F., Yost, H.J., Virshup, D.M. EMBO J. (2007) [Pubmed]
  8. Diversin regulates heart formation and gastrulation movements in development. Moeller, H., Jenny, A., Schaeffer, H.J., Schwarz-Romond, T., Mlodzik, M., Hammerschmidt, M., Birchmeier, W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Drosophila split ends homologue SHARP functions as a positive regulator of Wnt/beta-catenin/T-cell factor signaling in neoplastic transformation. Feng, Y., Bommer, G.T., Zhai, Y., Akyol, A., Hinoi, T., Winer, I., Lin, H.V., Cadigan, K.M., Cho, K.R., Fearon, E.R. Cancer Res. (2007) [Pubmed]
  10. Isolation and expression of two novel Wnt/wingless gene homologues in Drosophila. Russell, J., Gennissen, A., Nusse, R. Development (1992) [Pubmed]
  11. 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]
  12. WNT/Frizzled signaling in eye development and disease. de Iongh, R.U., Abud, H.E., Hime, G.R. Front. Biosci. (2006) [Pubmed]
  13. Developmental stage-specific biphasic roles of Wnt/beta-catenin signaling in cardiomyogenesis and hematopoiesis. Naito, A.T., Shiojima, I., Akazawa, H., Hidaka, K., Morisaki, T., Kikuchi, A., Komuro, I. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  14. Direct flight muscles in Drosophila develop from cells with characteristics of founders and depend on DWnt-2 for their correct patterning. Kozopas, K.M., Nusse, R. Dev. Biol. (2002) [Pubmed]
  15. Mammalian and Drosophila cells adhere to the laminin alpha4 LG4 domain through syndecans, but not glypicans. Yamashita, H., Goto, A., Kadowaki, T., Kitagawa, Y. Biochem. J. (2004) [Pubmed]
  16. SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice. Ma, Y., Cui, W., Yang, J., Qu, J., Di, C., Amin, H.M., Lai, R., Ritz, J., Krause, D.S., Chai, L. Blood (2006) [Pubmed]
  17. 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]
  18. Early requirement of the transcriptional activator Sox9 for neural crest specification in Xenopus. Lee, Y.H., Aoki, Y., Hong, C.S., Saint-Germain, N., Credidio, C., Saint-Jeannet, J.P. Dev. Biol. (2004) [Pubmed]
 
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