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Gene Review

Wnt7a  -  wingless-type MMTV integration site family...

Mus musculus

Synonyms: AI849442, Protein Wnt-7a, Wnt-7a, px, tw
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Disease relevance of Wnt7a

  • The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout) [1].
  • Members of the Wnt family of signaling molecules are important in cell specification and epithelial-mesenchymal interactions, and targeted gene deletion of Wnt-7a in mice results in complete absence of uterine glands and infertility [2].

High impact information on Wnt7a

  • Wnt-7a mutant mice show a delay in the morphological maturation of glomerular rosettes and in the accumulation of synapsin I [3].
  • Fetal exposure to DES results in de-regulation of Wnt7a during uterine morphogenesis [4].
  • Wnt7a, which is expressed in dorsal ectoderm, provides the signal required for Shh expression and formation of posterior structures [5].
  • Wnt7a-deficient females are infertile because of abnormal development of the oviduct and uterus, both of which are Müllerian duct derivatives [6].
  • Therefore, we propose that signalling by Wnt-7a allows sexually dimorphic development of the Müllerian ducts [6].

Biological context of Wnt7a

  • We suggest a model whereby, in En1 mutants, ectopic ventral Wnt7a and/or Lmx1b expression leads to the transformation of ventral cells in the broadened AER to a more dorsal phenotype [7].
  • Although Wnt7a down-regulation is transient after estrogenic exposure, subsequent morphologic changes became more pronounced during postnatal and adult life, suggesting that the female reproductive tract is permanently reprogrammed after exposure even to weak estrogenic compounds [8].
  • Wnt7a is a suppressor of cell death in the female reproductive tract and is required for postnatal and estrogen-mediated growth [9].
  • In addition, Wnt7a heterozygous mice were more sensitive to PCB exposure, revealing an important genetic predisposition to risks of environmental endocrine disruptors [8].
  • Exposure to the potent estrogen-agonist diethylstilbestrol (DES) leads to an increase in cell proliferation in the uterus in wild-type as well as in mutant uteri, indicating that Wnt7a is not required in mediating cell proliferation [9].

Anatomical context of Wnt7a


Associations of Wnt7a with chemical compounds

  • The morphologic changes that were elicited by PCBs and DES were different immediately after exposure, suggesting that Wnt7a-independent pathways are also activated by one or both of these compounds [8].
  • In contrast, we observe that Wnt7a mutant uteri display high levels of cell death in response to DES, whereas wild-type uteri display almost no cell death, revealing that Wnt7a plays a key role as a cell death suppressor [9].
  • To test the hypothesis that PCBs act as weak estrogens, we injected neonatal mice with a commercial PCB mixture (Aroclor 1254) or with low levels of DES and measured effects of exposure on Wnt7a expression and uterine morphology [8].
  • Pilot experiments showed a negative effect of Wnt-7a on the proliferation of three rodent chondrogenic cell lines, RCJ3.1(C5.18), CFK-2, and C1 [14].
  • Based on analyses of the axonal cytoskeleton, a model is proposed in which Wnt-7a induces axonal remodelling by inhibiting glycogen synthase kinase-3 beta (GSK-3 beta), a serine/threonine kinase [15].

Physical interactions of Wnt7a

  • En1 and Wnt7a interact with Dkk1 during limb development in the mouse [16].
  • Overexpression of Wnt7a or of a stabilized form of beta-catenin in mouse cortical NPC cultures induced neuronal differentiation even in the presence of Fgf2, a self-renewal-promoting factor in this system [17].

Regulatory relationships of Wnt7a


Other interactions of Wnt7a

  • In contrast, expression of Drosophila en in the embryonic limbs of En1 mutants does not lead to repression of Wnt7a in the embryonic ventral ectoderm or full rescue of the embryonic dorsal/ventral patterning defects [22].
  • We suggest that Fgfr2 is required for AER differentiation, as well as for En1 and Wnt7a expression [23].
  • In addition, two previously described Wnt genes, Wnt5a and Wnt7a, were detected in RT-PCR products [24].
  • Wnt-6 and Wnt-7a produced weak morphological changes [25].
  • Wnt7a and Wnt7b mRNAs were expressed in three out of four cell lines (RL95-2, HEC-1-A and Ishikawa) [26].


  1. Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome. Woods, C.G., Stricker, S., Seemann, P., Stern, R., Cox, J., Sherridan, E., Roberts, E., Springell, K., Scott, S., Karbani, G., Sharif, S.M., Toomes, C., Bond, J., Kumar, D., Al-Gazali, L., Mundlos, S. Am. J. Hum. Genet. (2006) [Pubmed]
  2. Identification, characterization, and regulation of the canonical Wnt signaling pathway in human endometrium. Tulac, S., Nayak, N.R., Kao, L.C., Van Waes, M., Huang, J., Lobo, S., Germeyer, A., Lessey, B.A., Taylor, R.N., Suchanek, E., Giudice, L.C. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  3. Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Hall, A.C., Lucas, F.R., Salinas, P.C. Cell (2000) [Pubmed]
  4. Fetal exposure to DES results in de-regulation of Wnt7a during uterine morphogenesis. Miller, C., Degenhardt, K., Sassoon, D.A. Nat. Genet. (1998) [Pubmed]
  5. Interaction between the signaling molecules WNT7a and SHH during vertebrate limb development: dorsal signals regulate anteroposterior patterning. Yang, Y., Niswander, L. Cell (1995) [Pubmed]
  6. Sexually dimorphic development of the mammalian reproductive tract requires Wnt-7a. Parr, B.A., McMahon, A.P. Nature (1998) [Pubmed]
  7. Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs. Loomis, C.A., Kimmel, R.A., Tong, C.X., Michaud, J., Joyner, A.L. Development (1998) [Pubmed]
  8. PCBs exert an estrogenic effect through repression of the Wnt7a signaling pathway in the female reproductive tract. Ma, R., Sassoon, D.A. Environ. Health Perspect. (2006) [Pubmed]
  9. Wnt7a is a suppressor of cell death in the female reproductive tract and is required for postnatal and estrogen-mediated growth. Carta, L., Sassoon, D. Biol. Reprod. (2004) [Pubmed]
  10. Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5. Tajbakhsh, S., Borello, U., Vivarelli, E., Kelly, R., Papkoff, J., Duprez, D., Buckingham, M., Cossu, G. Development (1998) [Pubmed]
  11. Wnt5a is required for proper epithelial-mesenchymal interactions in the uterus. Mericskay, M., Kitajewski, J., Sassoon, D. Development (2004) [Pubmed]
  12. Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue. Huguet, E.L., McMahon, J.A., McMahon, A.P., Bicknell, R., Harris, A.L. Cancer Res. (1994) [Pubmed]
  13. The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice. Grove, E.A., Tole, S., Limon, J., Yip, L., Ragsdale, C.W. Development (1998) [Pubmed]
  14. Wnts differentially regulate colony growth and differentiation of chondrogenic rat calvaria cells. Bergwitz, C., Wendlandt, T., Kispert, A., Brabant, G. Biochim. Biophys. Acta (2001) [Pubmed]
  15. Wnt factors in axonal remodelling and synaptogenesis. Salinas, P.C. Biochem. Soc. Symp. (1999) [Pubmed]
  16. En1 and Wnt7a interact with Dkk1 during limb development in the mouse. Adamska, M., MacDonald, B.T., Sarmast, Z.H., Oliver, E.R., Meisler, M.H. Dev. Biol. (2004) [Pubmed]
  17. The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Hirabayashi, Y., Itoh, Y., Tabata, H., Nakajima, K., Akiyama, T., Masuyama, N., Gotoh, Y. Development (2004) [Pubmed]
  18. The role of Engrailed in establishing the dorsoventral axis of the chick limb. Logan, C., Hornbruch, A., Campbell, I., Lumsden, A. Development (1997) [Pubmed]
  19. 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]
  20. Analysis of Fz10 expression in mouse embryos. Nunnally, A.P., Parr, B.A. Dev. Genes Evol. (2004) [Pubmed]
  21. Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release. Ahmad-Annuar, A., Ciani, L., Simeonidis, I., Herreros, J., Fredj, N.B., Rosso, S.B., Hall, A., Brickley, S., Salinas, P.C. J. Cell Biol. (2006) [Pubmed]
  22. Drosophila engrailed can substitute for mouse Engrailed1 function in mid-hindbrain, but not limb development. Hanks, M.C., Loomis, C.A., Harris, E., Tong, C.X., Anson-Cartwright, L., Auerbach, A., Joyner, A. Development (1998) [Pubmed]
  23. Novel roles of Fgfr2 in AER differentiation and positioning of the dorsoventral limb interface. Gorivodsky, M., Lonai, P. Development (2003) [Pubmed]
  24. 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]
  25. Transformation by Wnt family proteins correlates with regulation of beta-catenin. Shimizu, H., Julius, M.A., Giarré, M., Zheng, Z., Brown, A.M., Kitajewski, J. Cell Growth Differ. (1997) [Pubmed]
  26. 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]
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