Gene Symbol: Wnt5a
Description: wingless-type MMTV integration site family, member 5A
Alias: 8030457G12Rik, Wnt-5a, protein Wnt-5a, wingless-related MMTV integration site 5A
Species: mouse
Products:     Wnt5a

Top Publications

  1. Schleiffarth J, Person A, Martinsen B, Sukovich D, Neumann A, Baker C, et al. Wnt5a is required for cardiac outflow tract septation in mice. Pediatr Res. 2007;61:386-91 pubmed
    ..We show for the first time that a mutation in Wnt5a in mice leads to PTA...
  2. Gao B, Song H, Bishop K, Elliot G, Garrett L, English M, et al. Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2. Dev Cell. 2011;20:163-76 pubmed publisher
    ..In the limb bud, Wnt5a signaling gradient controls limb elongation by establishing PCP in chondrocytes along the proximal-distal axis ..
  3. Liu G, Bafico A, Aaronson S. The mechanism of endogenous receptor activation functionally distinguishes prototype canonical and noncanonical Wnts. Mol Cell Biol. 2005;25:3475-82 pubmed
    ..Here, we tandemly linked noncanonical Wnt5a with the C-terminal half of Dickkopf-2 (Dkk2C), a distinct ligand of the Wnt coreceptor LRP5/6...
  4. Yamamoto S, Nishimura O, Misaki K, Nishita M, Minami Y, Yonemura S, et al. Cthrc1 selectively activates the planar cell polarity pathway of Wnt signaling by stabilizing the Wnt-receptor complex. Dev Cell. 2008;15:23-36 pubmed publisher
    ..These results suggest that Cthrc1 is a Wnt cofactor protein that selectively activates the Wnt/PCP pathway by stabilizing ligand-receptor interaction. ..
  5. Wawrzak D, Metioui M, Willems E, Hendrickx M, De Genst E, Leyns L. Wnt3a binds to several sFRPs in the nanomolar range. Biochem Biophys Res Commun. 2007;357:1119-23 pubmed
    ..These results provide the first measurement of binding affinity of sFRPs for a Wnt, which together with the measurement of antagonistic activity of sFRPs could help understand how sFRPs regulate Wnt signaling. ..
  6. Yamamoto H, Yoo S, Nishita M, Kikuchi A, Minami Y. Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2. Genes Cells. 2007;12:1215-23 pubmed
    The receptor tyrosine kinase Ror2 plays important roles in mediating non-canonical Wnt5a signaling by activating the Wnt-JNK pathway and inhibiting the beta-catenin-TCF pathway...
  7. Parish C, Castelo Branco G, Rawal N, Tonnesen J, Sorensen A, Salto C, et al. Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice. J Clin Invest. 2008;118:149-60 pubmed
    ..Mouse VM neurospheres (VMNs) expanded with FGF2, differentiated with sonic hedgehog and FGF8, and transfected with Wnt5a (VMN-Wnt5a) generated 10-fold more DA neurons than did conventional FGF2-treated VMNs...
  8. Dabdoub A, Donohue M, Brennan A, Wolf V, Montcouquiol M, Sassoon D, et al. Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea. Development. 2003;130:2375-84 pubmed
    ..We propose that Wnt signaling across the region of developing outer hair cells gives rise to planar polarity in the mammalian cochlea. ..
  9. Oue N, Sato A, Hasegawa Y, Yamamoto H, Matsubara A, Yasui W, et al. Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase. Oncogene. 2010;29:2036-46 pubmed publisher
    b>Wnt5a is a representative ligand that activates the beta-catenin-independent pathway in Wnt signaling...

More Information


  1. Perriton C, Powles N, Chiang C, Maconochie M, Cohn M. Sonic hedgehog signaling from the urethral epithelium controls external genital development. Dev Biol. 2002;247:26-46 pubmed
    ..In the absence of Shh signaling, Fgf8, Bmp2, Bmp4, Fgf10, and Wnt5a are downregulated, and apoptosis is enhanced in the genitalia...
  2. Halleskog C, Dijksterhuis J, Kilander M, Becerril Ortega J, Villaescusa J, Lindgren E, et al. Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation. J Neuroinflammation. 2012;9:111 pubmed
  3. Schulte G, Bryja V, Rawal N, Castelo Branco G, Sousa K, Arenas E. Purified Wnt-5a increases differentiation of midbrain dopaminergic cells and dishevelled phosphorylation. J Neurochem. 2005;92:1550-3 pubmed
    ..Furthermore, we identify dishevelled as a key player in transducing both Wnt canonical and non-canonical signals in dopaminergic cells. ..
  4. Li X, Oghi K, Zhang J, Krones A, Bush K, Glass C, et al. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature. 2003;426:247-54 pubmed
  5. Topol L, Jiang X, Choi H, Garrett Beal L, Carolan P, Yang Y. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol. 2003;162:899-908 pubmed
    ..Furthermore, we provide evidence that Wnt-5a also acts in vivo to promote beta-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation. ..
  6. Hu B, Lefort K, Qiu W, Nguyen B, Rajaram R, Castillo E, et al. Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis. Genes Dev. 2010;24:1519-32 pubmed publisher
    ..Similar consequences on hair follicle differentiation result from deletion of Wnt5a, a specific dermal papilla signature gene that we found to be under direct Notch/CSL control in these cells...
  7. Roarty K, Serra R. Wnt5a is required for proper mammary gland development and TGF-beta-mediated inhibition of ductal growth. Development. 2007;134:3929-39 pubmed
    ..Tgfbeta) regulates the expression of a non-canonical signaling member of the wingless-related protein family, Wnt5a. Loss of Wnt5a expression has been associated with poor prognosis in breast cancer patients; however, data are ..
  8. Orelio C, Dzierzak E. Identification of 2 novel genes developmentally regulated in the mouse aorta-gonad-mesonephros region. Blood. 2003;101:2246-9 pubmed
    ..The identification of differentially expressed genes in the AGM region should yield further insights into the development of this tissue and into the emergence and regulation of HSCs...
  9. Yu J, Kim J, Song G, Jung J. Increase in proliferation and differentiation of neural progenitor cells isolated from postnatal and adult mice brain by Wnt-3a and Wnt-5a. Mol Cell Biochem. 2006;288:17-28 pubmed
    ..The PKC inhibitor completely blocked the Wnt-5a effect on neuronal differentiation in NPCs. These findings suggest that Wnt-3a and Wnt-5a each have distinct effects on the proliferation and differentiation of NPCs in postnatal mice. ..
  10. Maeda K, Kobayashi Y, Udagawa N, Uehara S, Ishihara A, Mizoguchi T, et al. Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. Nat Med. 2012;18:405-12 pubmed publisher
    ..b>Wnt5a activates noncanonical Wnt signaling through receptor tyrosine kinase-like orphan receptor (Ror) proteins...
  11. Sinha T, Wang B, Evans S, Wynshaw Boris A, Wang J. Disheveled mediated planar cell polarity signaling is required in the second heart field lineage for outflow tract morphogenesis. Dev Biol. 2012;370:135-44 pubmed publisher
    ..Mutating the core PCP gene Vangl2 and non-canonical Wnt gene Wnt5a recapitulated the OFT morphogenesis defects observed in Dvl1/2 mutants...
  12. Satoh W, Gotoh T, Tsunematsu Y, Aizawa S, Shimono A. Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis. Development. 2006;133:989-99 pubmed
    ..This study suggests that Wnt regulation by Sfrp1 and Sfrp2 is required for embryonic patterning. ..
  13. Pereira C, Schaer D, Bachli E, Kurrer M, Schoedon G. Wnt5A/CaMKII signaling contributes to the inflammatory response of macrophages and is a target for the antiinflammatory action of activated protein C and interleukin-10. Arterioscler Thromb Vasc Biol. 2008;28:504-10 pubmed publisher
    ..interferon (IFN)-gamma in the presence or absence of recombinant activated protein C (APC) or IL-10 and identified Wnt5A as one of the transcripts most highly induced by LPS/IFN-gamma and suppressed by APC and IL-10...
  14. Andersson E, Prakash N, Cajanek L, Minina E, Bryja V, Bryjova L, et al. Wnt5a regulates ventral midbrain morphogenesis and the development of A9-A10 dopaminergic cells in vivo. PLoS ONE. 2008;3:e3517 pubmed publisher
    b>Wnt5a is a morphogen that activates the Wnt/planar cell polarity (PCP) pathway and serves multiple functions during development...
  15. Liu Y, Shi J, Lu C, Wang Z, Lyuksyutova A, Song X, et al. Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract. Nat Neurosci. 2005;8:1151-9 pubmed
    ..Intrathecal injection of anti-Ryk blocked the posterior growth of CST axons. Therefore, Wnt proteins may have a general role in anterior-posterior guidance of multiple classes of axons. ..
  16. Liang H, Chen Q, Coles A, Anderson S, Pihan G, Bradley A, et al. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell. 2003;4:349-60 pubmed
    b>Wnt5a is a member of the Wnt family of secreted glycoproteins that play essential organizing roles in development. Similar to other Wnt members, Wnt5a can upregulate cell proliferation and has been proposed to have oncogenic function...
  17. Bryja V, Schulte G, Rawal N, Grahn A, Arenas E. Wnt-5a induces Dishevelled phosphorylation and dopaminergic differentiation via a CK1-dependent mechanism. J Cell Sci. 2007;120:586-95 pubmed
  18. Fenstermaker A, Prasad A, Bechara A, Adolfs Y, Tissir F, Goffinet A, et al. Wnt/planar cell polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem. J Neurosci. 2010;30:16053-64 pubmed publisher
    ..The only known ligands for planar cell polarity signaling are Wnt proteins. In culture, Wnt5a attracts 5-HT but repels mdDA axons, and Wnt7b attracts mdDA axons...
  19. Cohen E, Miller M, Wang Z, Moon R, Morrisey E. Wnt5a and Wnt11 are essential for second heart field progenitor development. Development. 2012;139:1931-40 pubmed publisher
    ..We show that two non-canonical Wnt ligands, Wnt5a and Wnt11, are co-required to regulate second heart field development in mice...
  20. Witze E, Litman E, Argast G, Moon R, Ahn N. Wnt5a control of cell polarity and directional movement by polarized redistribution of adhesion receptors. Science. 2008;320:365-9 pubmed publisher
    ..We show that acute responses to Wnt5a involve recruitment of actin, myosin IIB, Frizzled 3, and melanoma cell adhesion molecule into an intracellular ..
  21. Parr B, Shea M, Vassileva G, McMahon A. Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development. 1993;119:247-61 pubmed
    ..We discuss the significance of these patterns of restricted and partially overlapping domains of expression with respect to the putative function of Wnt signalling in early CNS and limb development. ..
  22. Buckley S, Ulloa Montoya F, Abts D, Oostendorp R, Dzierzak E, Ekker S, et al. Maintenance of HSC by Wnt5a secreting AGM-derived stromal cell line. Exp Hematol. 2011;39:114-123.e1-5 pubmed publisher
    ..As we found that Wnt5a was significantly higher expressed in UG26-1B6 than EL08-1D2 cells, we added Wnt5a to EL08-1D2 transwell cultures ..
  23. Yamaguchi T, Bradley A, McMahon A, Jones S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development. 1999;126:1211-23 pubmed
    ..b>Wnt5a may regulate these processes since it is expressed in a gradient at the caudal end of the growing embryo during ..
  24. Austin T, Solar G, Ziegler F, Liem L, Matthews W. A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells. Blood. 1997;89:3624-35 pubmed
    ..We conclude that WNTs stimulate the survival/proliferation of hematopoietic progenitors, demonstrating that WNTs comprise a novel class of hematopoietic cell regulators. ..
  25. Jung Y, Lee H, Kim S, Park J, Kim J, Suh P, et al. Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils. Exp Mol Med. 2013;45:e27 pubmed publisher
    b>Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (?-catenin-independent pathways). Human neutrophils expressed several Wnt5a receptors, such as Frizzled 2, 5 and 8...
  26. Ishikawa T, Tamai Y, Zorn A, Yoshida H, Seldin M, Nishikawa S, et al. Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development. 2001;128:25-33 pubmed
    ..5 days post coitum. Fzd5 specifically synergized with Wnt2, Wnt5a and Wnt10b in ectopic axis induction assays in Xenopus embryos...
  27. Bilkovski R, Schulte D, Oberhauser F, Gomolka M, Udelhoven M, Hettich M, et al. Role of WNT-5a in the determination of human mesenchymal stem cells into preadipocytes. J Biol Chem. 2010;285:6170-8 pubmed publisher
    ..Our data suggest that WNT-5a is necessary to maintain osteogenic potential of MSC and that inhibition of WNT-5a signaling therefore plays a role in their determination into PA in humans. ..
  28. O Connell M, Fiori J, Xu M, Carter A, Frank B, Camilli T, et al. The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma. Oncogene. 2010;29:34-44 pubmed publisher
    ..As ROR2 has been shown to specifically interact with the non-canonical Wnt ligand, Wnt5A, this corroborates our earlier data implicating Wnt5A as a mediator of melanoma metastasis...
  29. He F, Xiong W, Yu X, Espinoza Lewis R, Liu C, Gu S, et al. Wnt5a regulates directional cell migration and cell proliferation via Ror2-mediated noncanonical pathway in mammalian palate development. Development. 2008;135:3871-9 pubmed publisher
    ..Here, we show that Wnt5a and its receptor Ror2 are expressed in a graded manner along the AP axis of the palate...
  30. Nomachi A, Nishita M, Inaba D, Enomoto M, Hamasaki M, Minami Y. Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A. J Biol Chem. 2008;283:27973-81 pubmed publisher
    The receptor tyrosine kinase Ror2 has recently been shown to act as an alternative receptor or coreceptor for Wnt5a and to mediate Wnt5a-induced migration of cultured cells...
  31. Zhu X, Zhu H, Zhang L, Huang S, Cao J, Ma G, et al. Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis. Dev Biol. 2012;365:328-38 pubmed publisher
    ..Wls prevented the differentiation of distal mesenchyme and arrested limb outgrowth, most likely by affecting Wnt5a function...
  32. van Amerongen R, Fuerer C, Mizutani M, Nusse R. Wnt5a can both activate and repress Wnt/?-catenin signaling during mouse embryonic development. Dev Biol. 2012;369:101-14 pubmed publisher
    ..generation of a novel, inducible transgenic mouse model that allows spatiotemporal control over the expression of Wnt5a, a protein implicated in many developmental processes and multiple Wnt-signaling responses...
  33. Burrus L, McMahon A. Biochemical analysis of murine Wnt proteins reveals both shared and distinct properties. Exp Cell Res. 1995;220:363-73 pubmed
    ..Whereas addition of suramin to COS cell cultures significantly increases the levels of all six Wnts in the medium, the addition of heparin only influences the levels of Wnt-1, Wnt-6, and Wnt-7b. ..
  34. Depew M, Lufkin T, Rubenstein J. Specification of jaw subdivisions by Dlx genes. Science. 2002;298:381-5 pubmed
    ..We suggest that nested Dlx expression in the arches patterns their proximodistal axes. Evolutionary acquisition and subsequent refinement of jaws may have been dependent on modification of Dlx expression. ..
  35. Maiti G, Naskar D, Sen M. The Wingless homolog Wnt5a stimulates phagocytosis but not bacterial killing. Proc Natl Acad Sci U S A. 2012;109:16600-5 pubmed publisher
    ..Unregulated phagocytosis can lead to pathological conditions. In the current study we have demonstrated that Wnt5a stimulates phagocytosis through PI3 kinase-Rac1 and lipid-raft-dependent processes...
  36. Blumenthal A, Ehlers S, Lauber J, Buer J, Lange C, Goldmann T, et al. The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation. Blood. 2006;108:965-73 pubmed
    Microarray--assisted gene--expression screens of human macrophages revealed WNT5A, a homolog of Wingless, a key regulator of Drosophila melanogaster embryonic segmentation and patterning, to be consistently up-regulated following ..
  37. Yamagata K, Li X, Ikegaki S, Oneyama C, Okada M, Nishita M, et al. Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP-13) expression. J Biol Chem. 2012;287:1588-99 pubmed publisher
    It has been shown that constitutively active Wnt5a-Ror2 signaling in osteosarcoma cell lines plays crucial roles in induced expression of matrix metalloproteinase-13 (MMP-13), required for their invasiveness; however, it remains largely ..
  38. Galceran J, Farinas I, Depew M, Clevers H, Grosschedl R. Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice. Genes Dev. 1999;13:709-17 pubmed
    ..Together, these data provide evidence for a redundant role of LEF-1 and TCF-1 in Wnt signaling during mouse development. ..
  39. Lickert H, Kispert A, Kutsch S, Kemler R. Expression patterns of Wnt genes in mouse gut development. Mech Dev. 2001;105:181-4 pubmed
    ..5 and 16.5 of embryonic development. The expression of Wnt5a is confined to the mesenchymal compartment, while expression of Wnt4 is found both in the intestinal epithelium ..
  40. Masckauchan T, Agalliu D, Vorontchikhina M, Ahn A, Parmalee N, Li C, et al. Wnt5a signaling induces proliferation and survival of endothelial cells in vitro and expression of MMP-1 and Tie-2. Mol Biol Cell. 2006;17:5163-72 pubmed
    Wnts are lipid-modified secreted glycoproteins that regulate diverse biological processes. We report that Wnt5a, which functions in noncanonical Wnt signaling, has activity on endothelial cells...
  41. Yamada M, Udagawa J, Matsumoto A, Hashimoto R, Hatta T, Nishita M, et al. Ror2 is required for midgut elongation during mouse development. Dev Dyn. 2010;239:941-53 pubmed publisher
    The receptor tyrosine kinase Ror2 acts as a receptor for Wnt5a to mediate noncanonical Wnt signaling, and it plays essential roles in morphogenesis...
  42. Chen W, ten Berge D, Brown J, Ahn S, Hu L, Miller W, et al. Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4. Science. 2003;301:1391-4 pubmed
    ..Endocytosis of Frizzled 4 (Fz4) in human embryonic kidney 293 cells was dependent on added Wnt5A protein and was accomplished by the multifunctional adaptor protein beta-arrestin 2 (betaarr2), which was ..
  43. Phillips H, Murdoch J, Chaudhry B, Copp A, Henderson D. Vangl2 acts via RhoA signaling to regulate polarized cell movements during development of the proximal outflow tract. Circ Res. 2005;96:292-9 pubmed
  44. Parr B, Cornish V, Cybulsky M, McMahon A. Wnt7b regulates placental development in mice. Dev Biol. 2001;237:324-32 pubmed
    ..Wnt7b also is required for normal organization of cells in the chorionic plate. Thus, Wnt7b signaling is central to the early stages of placental development in mammals. ..
  45. Lehtinen M, Zappaterra M, Chen X, Yang Y, Hill A, Lun M, et al. The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron. 2011;69:893-905 pubmed publisher
    ..The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions...
  46. Castelo Branco G, Wagner J, Rodriguez F, Kele J, Sousa K, Rawal N, et al. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc Natl Acad Sci U S A. 2003;100:12747-52 pubmed
    ..These findings indicate that Wnts are key regulators of proliferation and differentiation of DA precursors during VM neurogenesis and that different Wnts have specific and unique activity profiles. ..
  47. Endo Y, Beauchamp E, Woods D, Taylor W, Toretsky J, Uren A, et al. Wnt-3a and Dickkopf-1 stimulate neurite outgrowth in Ewing tumor cells via a Frizzled3- and c-Jun N-terminal kinase-dependent mechanism. Mol Cell Biol. 2008;28:2368-79 pubmed publisher
    ..Our data demonstrate that Fzd3, Dvl, and JNK activity mediate Wnt-dependent neurite outgrowth and that ESFT cell lines will be useful experimental models for the study of Wnt-dependent neurite extension. ..
  48. Qian D, Jones C, Rzadzinska A, Mark S, Zhang X, Steel K, et al. Wnt5a functions in planar cell polarity regulation in mice. Dev Biol. 2007;306:121-33 pubmed
    ..We show that Wnt5a forms a reciprocal expression pattern with a Wnt antagonist, the secreted frizzled-related protein 3 (Sfrp3 or ..
  49. Takada S, Stark K, Shea M, Vassileva G, McMahon J, McMahon A. Wnt-3a regulates somite and tailbud formation in the mouse embryo. Genes Dev. 1994;8:174-89 pubmed
    ..We suggest that dysmorphology is secondary to the mesodermal and axial defects and that dorsal patterning of the CNS may be regulated by inductive signals arising from surface ectoderm. ..
  50. Dissanayake S, Olkhanud P, O Connell M, Carter A, French A, Camilli T, et al. Wnt5A regulates expression of tumor-associated antigens in melanoma via changes in signal transducers and activators of transcription 3 phosphorylation. Cancer Res. 2008;68:10205-14 pubmed publisher
    ..In this study, we show that the noncanonical Wnt ligand, Wnt5A, can increase melanoma metastasis in vivo while down-regulating the expression of tumor-associated antigens ..
  51. Reddy S, Andl T, Bagasra A, Lu M, Epstein D, Morrisey E, et al. Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mech Dev. 2001;107:69-82 pubmed
    ..Among these, we find that Wnt5a is expressed in the developing dermal condensate of wild type but not Sonic hedgehog (Shh)-null embryos, ..
  52. Takada R, Hijikata H, Kondoh H, Takada S. Analysis of combinatorial effects of Wnts and Frizzleds on beta-catenin/armadillo stabilization and Dishevelled phosphorylation. Genes Cells. 2005;10:919-28 pubmed