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Gene Review

Wnt5a  -  wingless-type MMTV integration site family...

Mus musculus

Synonyms: 8030457G12Rik, Protein Wnt-5a, Wnt-5a
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Disease relevance of Wnt5a

  • The proportion of embryos showing reduced expression and almost undetectable expression of Wnt5a reflects the proportions of tail defects and spina bifida seen at later stages [1].
  • Analysis of younger embryos revealed that prior to the stage at which embryos at risk of developing neural tube defects can be detected, the same proportion of ct/ct embryos shows reduced Wnt5a expression [1].
  • RESULTS: Both Ror2-/- and Wnt5a-/- mice exhibit dwarfism, facial abnormalities, short limbs and tails, dysplasia of lungs and genitals, and ventricular septal defects [2].
  • Wnt5a hemizygous mice develop myeloid leukemias and B cell lymphomas that are clonal in origin and display loss of Wnt5a function in tumor tissues [3].
  • Wnt5a is the first member of the Wnt family to demonstrate overexpression in human breast cancer [4].

Psychiatry related information on Wnt5a


High impact information on Wnt5a

  • Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a [6].
  • In contrast, Wnt-5a primarily increased the proportion of Nurr1+ precursors that acquired a neuronal DA phenotype and up-regulated the expression of Ptx3 and c-ret mRNA [6].
  • The expression profiles of four murine frizzled homologs, Mfz3-7, were nearly identical to that of Wnt-5a and Wnt-10b [7].
  • In Foxf mutants, mesenchymal expression of Bmp4 is reduced, whereas Wnt5a expression is increased [8].
  • Data presented provide a mechanistic basis for how uterine stroma mediates both developmental and estrogen-mediated changes in the epithelium and demonstrates that Wnt5a is a key component in this process [9].

Chemical compound and disease context of Wnt5a

  • The Wnt5a signal is mediated by the orphan tyrosine kinase Ror2, is pertussis toxin insensitive, and does not influence cellular calcium levels [10].

Biological context of Wnt5a


Anatomical context of Wnt5a

  • Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus [9].
  • We showed that expression of matrix extracellular phosphoglycoprotein was induced by BMP-2 in Wnt3a over-expressing C2C12 cells but not in Wnt5a over-expressing C2C12 cells [14].
  • Wnt5a and 7b mRNA is broadly expressed in foregut mesenchyme starting around embryonic day 10 in mice [15].
  • Wnt4 was expressed in only one out of four cell lines (RL95-2), and Wnt5a was much lower [16].
  • This study suggests that the primary role of Wnt5a in the developing pituitary gland is in establishment of the shape of the gland [17].

Associations of Wnt5a with chemical compounds

  • Well before exfoliation is evident, FimH-mediated attachment suppresses transforming growth factor-beta (Bmp4) and Wnt5a/Ca(2+) signaling to promote subsequent differentiation of basal/intermediate cells [18].
  • No expression of the Wnt-4 and Wnt-5a genes is detectable in C57mg cells that are fully transformed by the activated tyrosine kinase oncogene Neu [19].

Physical interactions of Wnt5a


Regulatory relationships of Wnt5a


Other interactions of Wnt5a

  • These suggest that over-expression of Wnt5a disrupts epithelial-response to FGF10 [22].
  • The expression of Wnt5a is confined to the mesenchymal compartment, while expression of Wnt4 is found both in the intestinal epithelium and the mesenteric anlage [28].
  • In addition, two previously described Wnt genes, Wnt5a and Wnt7a, were detected in RT-PCR products [29].
  • Wnt7a was mapped to mouse Chr 6, Wnt5a to the centromeric region of Chr 14, and Wnt11 to Chr7 [29].
  • Prop1 and Hesx1 are also important for normal shape of the pituitary primordium, but their expression is unaltered in the Wnt5a mutants [17].
  • Genetic studies and in vitro organ culture assays further demonstrate a role for Ror2 in mediating Wnt5a signaling in the regulation of cell proliferation and migration during palate development [30].

Analytical, diagnostic and therapeutic context of Wnt5a


  1. Genetic patterning of the posterior neuropore region of curly tail mouse embryos: deficiency of Wnt5a expression. Gofflot, F., Hall, M., Morriss-Kay, G.M. Int. J. Dev. Biol. (1998) [Pubmed]
  2. The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Oishi, I., Suzuki, H., Onishi, N., Takada, R., Kani, S., Ohkawara, B., Koshida, I., Suzuki, K., Yamada, G., Schwabe, G.C., Mundlos, S., Shibuya, H., Takada, S., Minami, Y. Genes Cells (2003) [Pubmed]
  3. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Liang, H., Chen, Q., Coles, A.H., Anderson, S.J., Pihan, G., Bradley, A., Gerstein, R., Jurecic, R., Jones, S.N. Cancer Cell (2003) [Pubmed]
  4. Wnt5a cloning, expression, and up-regulation in human primary breast cancers. Lejeune, S., Huguet, E.L., Hamby, A., Poulsom, R., Harris, A.L. Clin. Cancer Res. (1995) [Pubmed]
  5. Embryonic stem cells prevent developmental cardiac defects in mice. Fraidenraich, D., Benezra, R. Nature clinical practice. Cardiovascular medicine. (2006) [Pubmed]
  6. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Castelo-Branco, G., Wagner, J., Rodriguez, F.J., Kele, J., Sousa, K., Rawal, N., Pasolli, H.A., Fuchs, E., Kitajewski, J., Arenas, E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  7. A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Austin, T.W., Solar, G.P., Ziegler, F.C., Liem, L., Matthews, W. Blood (1997) [Pubmed]
  8. Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production. Ormestad, M., Astorga, J., Landgren, H., Wang, T., Johansson, B.R., Miura, N., Carlsson, P. Development (2006) [Pubmed]
  9. Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus. Mericskay, M., Kitajewski, J., Sassoon, D. Development (2004) [Pubmed]
  10. Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. Mikels, A.J., Nusse, R. PLoS Biol. (2006) [Pubmed]
  11. Regulation of outgrowth and apoptosis for the terminal appendage: external genitalia development by concerted actions of BMP signaling [corrected]. Suzuki, K., Bachiller, D., Chen, Y.P., Kamikawa, M., Ogi, H., Haraguchi, R., Ogino, Y., Minami, Y., Mishina, Y., Ahn, K., Crenshaw, E.B., Yamada, G. Development (2003) [Pubmed]
  12. Wnt proteins prevent apoptosis of both uncommitted osteoblast progenitors and differentiated osteoblasts by beta-catenin-dependent and -independent signaling cascades involving Src/ERK and phosphatidylinositol 3-kinase/AKT. Almeida, M., Han, L., Bellido, T., Manolagas, S.C., Kousteni, S. J. Biol. Chem. (2005) [Pubmed]
  13. Wnt5a participates in distal lung morphogenesis. Li, C., Xiao, J., Hormi, K., Borok, Z., Minoo, P. Dev. Biol. (2002) [Pubmed]
  14. Cross-talk between Wnt and bone morphogenetic protein 2 (BMP-2) signaling in differentiation pathway of C2C12 myoblasts. Nakashima, A., Katagiri, T., Tamura, M. J. Biol. Chem. (2005) [Pubmed]
  15. Expression patterns of Wnts, Frizzleds, sFRPs, and misexpression in transgenic mice suggesting a role for Wnts in pancreas and foregut pattern formation. Heller, R.S., Dichmann, D.S., Jensen, J., Miller, C., Wong, G., Madsen, O.D., Serup, P. Dev. Dyn. (2002) [Pubmed]
  16. Expression and hormone regulation of Wnt2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma. Bui, T.D., Zhang, L., Rees, M.C., Bicknell, R., Harris, A.L. Br. J. Cancer (1997) [Pubmed]
  17. WNT5A signaling affects pituitary gland shape. Cha, K.B., Douglas, K.R., Potok, M.A., Liang, H., Jones, S.N., Camper, S.A. Mech. Dev. (2004) [Pubmed]
  18. Molecular regulation of urothelial renewal and host defenses during infection with uropathogenic Escherichia coli. Mysorekar, I.U., Mulvey, M.A., Hultgren, S.J., Gordon, J.I. J. Biol. Chem. (2002) [Pubmed]
  19. Regulated expression of Wnt family members during proliferation of C57mg mammary cells. Olson, D.J., Papkoff, J. Cell Growth Differ. (1994) [Pubmed]
  20. Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells. Jönsson, M., Andersson, T. J. Cell. Sci. (2001) [Pubmed]
  21. Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Parr, B.A., Shea, M.J., Vassileva, G., McMahon, A.P. Development (1993) [Pubmed]
  22. Wnt5a regulates Shh and Fgf10 signaling during lung development. Li, C., Hu, L., Xiao, J., Chen, H., Li, J.T., Bellusci, S., Delanghe, S., Minoo, P. Dev. Biol. (2005) [Pubmed]
  23. Stromelysin-1 and mesothelin are differentially regulated by Wnt-5a and Wnt-1 in C57mg mouse mammary epithelial cells. Prieve, M.G., Moon, R.T. BMC Dev. Biol. (2003) [Pubmed]
  24. Purified Wnt-5a increases differentiation of midbrain dopaminergic cells and dishevelled phosphorylation. Schulte, G., Bryja, V., Rawal, N., Castelo-Branco, G., Sousa, K.M., Arenas, E. J. Neurochem. (2005) [Pubmed]
  25. Wnt5a inhibits canonical Wnt signaling in hematopoietic stem cells and enhances repopulation. Nemeth, M.J., Topol, L., Anderson, S.M., Yang, Y., Bodine, D.M. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  26. Wnt-5a induces Dishevelled phosphorylation and dopaminergic differentiation via a CK1-dependent mechanism. Bryja, V., Schulte, G., Rawal, N., Grahn, A., Arenas, E. J. Cell. Sci. (2007) [Pubmed]
  27. Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A. Nomachi, A., Nishita, M., Inaba, D., Enomoto, M., Hamasaki, M., Minami, Y. J. Biol. Chem. (2008) [Pubmed]
  28. Expression patterns of Wnt genes in mouse gut development. Lickert, H., Kispert, A., Kutsch, S., Kemler, R. Mech. Dev. (2001) [Pubmed]
  29. Isolation and genetic mapping of two novel members of the murine Wnt gene family, Wnt11 and Wnt12, and the mapping of Wnt5a and Wnt7a. Adamson, M.C., Dennis, C., Delaney, S., Christiansen, J., Monkley, S., Kozak, C.A., Wainwright, B. Genomics (1994) [Pubmed]
  30. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. He, F., Xiong, W., Yu, X., Espinoza-Lewis, R., Liu, C., Gu, S., Nishita, M., Suzuki, K., Yamada, G., Minami, Y., Chen, Y. Development (2008) [Pubmed]
  31. Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice. Almind, K., Kahn, C.R. Diabetes (2004) [Pubmed]
  32. Rapid identification of homeodomain binding sites in the Wnt-5a gene using an immunoprecipitation strategy. Iler, N., Abate-Shen, C. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
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