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Gene Review

Wnt3  -  wingless-type MMTV integration site family...

Mus musculus

Synonyms: Int-4, Proto-oncogene Int-4, Proto-oncogene Wnt-3, Wnt-3
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Disease relevance of Wnt3


High impact information on Wnt3

  • In contrast, signaling by the growth factors Nodal and Wnt3, which are also essential during mouse gastrulation, appears to be normal in lzme embryos [4].
  • This phenotype was similar to Wnt-3(-/-) and LRP5/6 double-knockout embryos [5].
  • Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge [6].
  • In this study, we demonstrate that Wnt3, which is expressed ubiquitously throughout the limb ectoderm, is essential for normal limb development and plays a critical role in the establishment of the AER [6].
  • This family includes Wnt-1 and Wnt-3, both discovered as activated oncogenes in mouse mammary tumors [7].

Biological context of Wnt3

  • Beta-catenin regulates Cripto- and Wnt3-dependent gene expression programs in mouse axis and mesoderm formation [8].
  • With the addition of these balancers to the previously reported Trp53-Wnt3 balancer, most of mouse chromosome 11 is now available in balancer stocks [9].
  • Overexpression of Wnt3 was sufficient to cause a consistent increase in the number of embryoid bodies committing to haematopoiesis further strengthening the evidence that this protein can enhance haematopoietic commitment during in vitro differentiation of ES cells [10].
  • Expression of these constructs results in stunted hair growth, a phenotype that has also been observed in transgenic mice expressing Wnt3 and Dvl2 (Millar et al. 1999) [11].
  • The putative amino acid sequences of both proteins are almost 90% identical, but in situ hybridization to mouse embryo sections showed highly restricted patterns of expression of Wnt-3 and Wnt-3A, largely in separate areas in the developing nervous system [7].

Anatomical context of Wnt3


Regulatory relationships of Wnt3

  • Dlx-1 is expressed in a non-overlapping area immediately anterior to and abutting the Wnt-3 expressing domain, corresponding to the ventral thalamus [15].
  • We found that Wnt-3 is expressed during development of the cerebellum and that expression is restricted to the Purkinje cell layer in the adult [16].

Other interactions of Wnt3

  • A putative effector molecule for WNT3 signaling, the cytoplasmic protein Dishevelled 2 (DVL2), is normally present at high levels in a subset of cells in the outer root sheath and in precursor cells of the hair shaft cortex and cuticle which lie immediately adjacent to Wnt3-expressing cells [17].
  • Reciprocal patterns of expression are found within the dorsal thalamus for the Gbx-2 and Wnt-3 genes [18].
  • Progeny from an intersubspecies backcross were analyzed to position this locus, termed Shbg, between Il-3 and Int-4 in the middle of this chromosome [19].
  • Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis [1].
  • Our results reveal that neither Brachyury nor Wnt3 forms a ring of expression in the proximal epiblast as previously thought [13].

Analytical, diagnostic and therapeutic context of Wnt3


  1. Differential transformation of mammary epithelial cells by Wnt genes. Wong, G.T., Gavin, B.J., McMahon, A.P. Mol. Cell. Biol. (1994) [Pubmed]
  2. Insertional mutagenesis identifies a member of the Wnt gene family as a candidate oncogene in the mammary epithelium of int-2/Fgf-3 transgenic mice. Lee, F.S., Lane, T.F., Kuo, A., Shackleford, G.M., Leder, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Molecular cloning and characterization of human WNT3. Katoh, M. Int. J. Oncol. (2001) [Pubmed]
  4. Essential role of glycosaminoglycans in Fgf signaling during mouse gastrulation. García-García, M.J., Anderson, K.V. Cell (2003) [Pubmed]
  5. The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. Chen, H.J., Lin, C.M., Lin, C.S., Perez-Olle, R., Leung, C.L., Liem, R.K. Genes Dev. (2006) [Pubmed]
  6. Ectodermal Wnt3/beta-catenin signaling is required for the establishment and maintenance of the apical ectodermal ridge. Barrow, J.R., Thomas, K.R., Boussadia-Zahui, O., Moore, R., Kemler, R., Capecchi, M.R., McMahon, A.P. Genes Dev. (2003) [Pubmed]
  7. Expression of two members of the Wnt family during mouse development--restricted temporal and spatial patterns in the developing neural tube. Roelink, H., Nusse, R. Genes Dev. (1991) [Pubmed]
  8. Beta-catenin regulates Cripto- and Wnt3-dependent gene expression programs in mouse axis and mesoderm formation. Morkel, M., Huelsken, J., Wakamiya, M., Ding, J., van de Wetering, M., Clevers, H., Taketo, M.M., Behringer, R.R., Shen, M.M., Birchmeier, W. Development (2003) [Pubmed]
  9. Two new mouse chromosome 11 balancers. Klysik, J., Dinh, C., Bradley, A. Genomics (2004) [Pubmed]
  10. Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro: role of Wnt3 in enhancing haematopoietic differentiation. Lako, M., Lindsay, S., Lincoln, J., Cairns, P.M., Armstrong, L., Hole, N. Mech. Dev. (2001) [Pubmed]
  11. Plakoglobin suppresses epithelial proliferation and hair growth in vivo. Charpentier, E., Lavker, R.M., Acquista, E., Cowin, P. J. Cell Biol. (2000) [Pubmed]
  12. Expression of Wnt9b and activation of canonical Wnt signaling during midfacial morphogenesis in mice. Lan, Y., Ryan, R.C., Zhang, Z., Bullard, S.A., Bush, J.O., Maltby, K.M., Lidral, A.C., Jiang, R. Dev. Dyn. (2006) [Pubmed]
  13. Primitive streak formation in mice is preceded by localized activation of Brachyury and Wnt3. Rivera-Pérez, J.A., Magnuson, T. Dev. Biol. (2005) [Pubmed]
  14. Over- and ectopic expression of Wnt3 causes progressive loss of ameloblasts in postnatal mouse incisor teeth. Millar, S.E., Koyama, E., Reddy, S.T., Andl, T., Gaddapara, T., Piddington, R., Gibson, C.W. Connect. Tissue Res. (2003) [Pubmed]
  15. Regional expression of the Wnt-3 gene in the developing mouse forebrain in relationship to diencephalic neuromeres. Salinas, P.C., Nusse, R. Mech. Dev. (1992) [Pubmed]
  16. Maintenance of Wnt-3 expression in Purkinje cells of the mouse cerebellum depends on interactions with granule cells. Salinas, P.C., Fletcher, C., Copeland, N.G., Jenkins, N.A., Nusse, R. Development (1994) [Pubmed]
  17. WNT signaling in the control of hair growth and structure. Millar, S.E., Willert, K., Salinas, P.C., Roelink, H., Nusse, R., Sussman, D.J., Barsh, G.S. Dev. Biol. (1999) [Pubmed]
  18. Spatially restricted expression of Dlx-1, Dlx-2 (Tes-1), Gbx-2, and Wnt-3 in the embryonic day 12.5 mouse forebrain defines potential transverse and longitudinal segmental boundaries. Bulfone, A., Puelles, L., Porteus, M.H., Frohman, M.A., Martin, G.R., Rubenstein, J.L. J. Neurosci. (1993) [Pubmed]
  19. Genetic mapping of the gene for androgen-binding protein/sex hormone-binding globulin to mouse chromosome 11. Joseph, D.R., Adamson, M.C., Kozak, C.A. Cytogenet. Cell Genet. (1991) [Pubmed]
  20. Investigations of the genomic region that contains the clf1 mutation, a causal gene in multifactorial cleft lip and palate in mice. Juriloff, D.M., Harris, M.J., Dewell, S.L., Brown, C.J., Mager, D.L., Gagnier, L., Mah, D.G. Birth defects research. Part A, Clinical and molecular teratology. (2005) [Pubmed]
  21. Molecular cloning and characterization of mouse Wnt14b, clustered with mouse Wnt3 in mouse chromosome 11. Kirikoshi, H., Katoh, M. Int. J. Mol. Med. (2002) [Pubmed]
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