Gene Symbol: Wnt3a
Description: wingless-type MMTV integration site family, member 3A
Alias: Wnt-3a, protein Wnt-3a, vestigial tail, wingless-related MMTV integration site 3A
Species: mouse
Products:     Wnt3a

Top Publications

  1. Shimizu T, Kagawa T, Wada T, Muroyama Y, Takada S, Ikenaka K. Wnt signaling controls the timing of oligodendrocyte development in the spinal cord. Dev Biol. 2005;282:397-410 pubmed
    ..Addition of rmFz-8/Fc, a Wnt antagonist, increased the number of immature oligodendrocytes in the spinal cord explant culture, demonstrating that endogenous Wnt signaling controls oligodendrocyte development. ..
  2. Liu Z, Tang Y, Qiu T, Cao X, Clemens T. A dishevelled-1/Smad1 interaction couples WNT and bone morphogenetic protein signaling pathways in uncommitted bone marrow stromal cells. J Biol Chem. 2006;281:17156-63 pubmed
    ..Treatment with Wnt3a, but not BMP-2, stimulated Lef1-mediated transcriptional activity, whereas co-stimulation with both Wnt3a and BMP-..
  3. ten Berge D, Kurek D, Blauwkamp T, Koole W, Maas A, Eroglu E, et al. Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. Nat Cell Biol. 2011;13:1070-5 pubmed publisher
    ..Our results not only demonstrate that Wnt signals regulate the naive-to-primed pluripotency transition, but also identify Wnt as an essential and limiting ESC self-renewal factor. ..
  4. 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
    ..show, using surface plasmon resonance and purified proteins, that sFRP1, sFRP2, sFRP4, and Frzb bind directly to Wnt3a with affinities in the nanomolar range...
  5. Dunty W, Biris K, Chalamalasetty R, Taketo M, Lewandoski M, Yamaguchi T. Wnt3a/beta-catenin signaling controls posterior body development by coordinating mesoderm formation and segmentation. Development. 2008;135:85-94 pubmed
    Somitogenesis is thought to be controlled by a segmentation clock, which consists of molecular oscillators in the Wnt3a, Fgf8 and Notch pathways...
  6. 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. ..
  7. Cruciat C, Ohkawara B, Acebron S, Karaulanov E, Reinhard C, Ingelfinger D, et al. Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling. Science. 2010;327:459-63 pubmed publisher
    ..The results reveal an unsuspected role for the prorenin receptor, V-ATPase activity, and acidification during Wnt/beta-catenin signaling...
  8. Duncan A, Rattis F, DiMascio L, Congdon K, Pazianos G, Zhao C, et al. Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol. 2005;6:314-22 pubmed
    ..These data suggest that Notch signaling has a dominant function in inhibiting differentiation and provide a model for how HSCs may integrate multiple signals to maintain the stem cell state. ..
  9. Bikkavilli R, Feigin M, Malbon C. p38 mitogen-activated protein kinase regulates canonical Wnt-beta-catenin signaling by inactivation of GSK3beta. J Cell Sci. 2008;121:3598-607 pubmed publisher
    ..kinase (MAPK) pathways that might intersect with the canonical Wnt-beta-catenin signaling pathway in response to Wnt3a, we observed a strong activation of p38 MAPK in mouse F9 teratocarcinoma cells...

More Information


  1. Chu M, Ahn V, Choi H, Daniels D, Nusse R, Weis W. structural Studies of Wnts and identification of an LRP6 binding site. Structure. 2013;21:1235-42 pubmed publisher
    ..Structure-based mutational analysis of mouse Wnt3a shows that the linker between the N- and C-terminal domains is required for LRP6 binding...
  2. Muroyama Y, Fujihara M, Ikeya M, Kondoh H, Takada S. Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord. Genes Dev. 2002;16:548-53 pubmed
    ..Here, we demonstrate that absence of Wnt1 and Wnt3a, normally expressed in the roof plate, leads to diminished development of D1 and D2 neurons and a compensatory ..
  3. de Jesus Perez V, Alastalo T, Wu J, Axelrod J, Cooke J, Amieva M, et al. Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt-beta-catenin and Wnt-RhoA-Rac1 pathways. J Cell Biol. 2009;184:83-99 pubmed publisher
    ..These findings suggest that the recruitment of both canonical and noncanonical Wnt pathways is required in BMP-2-mediated angiogenesis. ..
  4. Almeida M, Han L, Bellido T, Manolagas S, Kousteni S. 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. J Biol Chem. 2005;280:41342-51 pubmed
    ..Serum withdrawal-induced apoptosis was prevented by the canonical Wnts (Wnt3a and Wnt1) and the noncanonical Wnt5a in all cell types...
  5. Aulehla A, Wehrle C, Brand Saberi B, Kemler R, Gossler A, Kanzler B, et al. Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev Cell. 2003;4:395-406 pubmed
    ..Moreover, Wnt3a is required for oscillating Notch signaling activity in the PSM...
  6. Rashbass P, Wilson V, Rosen B, Beddington R. Alterations in gene expression during mesoderm formation and axial patterning in Brachyury (T) embryos. Int J Dev Biol. 1994;38:35-44 pubmed
    ..This extension into ventromedial somite domains is more pronounced caudally, supporting a function for the notochord in ventralizing somites. ..
  7. 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
  8. Yamaguchi T, Takada S, Yoshikawa Y, Wu N, McMahon A. T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification. Genes Dev. 1999;13:3185-90 pubmed
    b>Wnt3a encodes a signal that is expressed in the primitive streak of the gastrulating mouse embryo and is required for paraxial mesoderm development. In its absence cells adopt ectopic neural fates...
  9. Lee J, Ishimoto A, Yanagawa S. Characterization of mouse dishevelled (Dvl) proteins in Wnt/Wingless signaling pathway. J Biol Chem. 1999;274:21464-70 pubmed
    ..These results are direct evidence that Dsh family proteins mediate a set of conserved biochemical processes in the Wnt/Wg signaling pathway. ..
  10. Greco T, Takada S, Newhouse M, McMahon J, McMahon A, Camper S. Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development. Genes Dev. 1996;10:313-24 pubmed
    Mice homozygous for the recessive mutation vestigial tail (vt), which arose spontaneously on Chromosome 11, exhibit vertebral abnormalities, including loss of caudal vertebrae leading to shortening of the tail...
  11. Kress E, Rezza A, Nadjar J, Samarut J, Plateroti M. The frizzled-related sFRP2 gene is a target of thyroid hormone receptor alpha1 and activates beta-catenin signaling in mouse intestine. J Biol Chem. 2009;284:1234-41 pubmed publisher
    ..Moreover, we describe in this study a novel mechanism of action of sFRP2, responsible for the activation of beta-catenin signaling. ..
  12. Blitzer J, Nusse R. A critical role for endocytosis in Wnt signaling. BMC Cell Biol. 2006;7:28 pubmed
    ..Moreover, as internalized Wnts transit partially through the transferrin recycling pathway, it is possible that a "signaling endosome" serves as a nexus for activated Wnt pathway components. ..
  13. Honda T, Yamamoto H, Ishii A, Inui M. PDZRN3 negatively regulates BMP-2-induced osteoblast differentiation through inhibition of Wnt signaling. Mol Biol Cell. 2010;21:3269-77 pubmed publisher
    ..Furthermore, the expression and Wnt3a-induced phosphorylation of LRP6 as well as the increase in the cytosolic abundance of ?-catenin induced by Wnt3a ..
  14. Nakaya M, Biris K, Tsukiyama T, Jaime S, Rawls J, Yamaguchi T. Wnt3a links left-right determination with segmentation and anteroposterior axis elongation. Development. 2005;132:5425-36 pubmed
    ..How morphogenesis is coupled to axis specification is not well understood. We demonstrate that Wnt3a is required for LR asymmetry...
  15. 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. ..
  16. Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol. 1998;14:59-88 pubmed
    ..Here we review recent data that have started to unravel the mechanisms of Wnt signaling. ..
  17. Doubravska L, Krausova M, Gradl D, Vojtechova M, Tumova L, Lukas J, et al. Fatty acid modification of Wnt1 and Wnt3a at serine is prerequisite for lipidation at cysteine and is essential for Wnt signalling. Cell Signal. 2011;23:837-48 pubmed publisher
    ..these modifications contribute to the secretion, extracellular movement and signalling activity of mouse Wnt1 and Wnt3a ligands. We revealed that O-linked acylation of serine is required for the subsequent S-palmitoylation of cysteine...
  18. Goh K, Yang J, Hynes R. Mesodermal defects and cranial neural crest apoptosis in alpha5 integrin-null embryos. Development. 1997;124:4309-19 pubmed
  19. Lickert H, Cox B, Wehrle C, Taketo M, Kemler R, Rossant J. Dissecting Wnt/beta-catenin signaling during gastrulation using RNA interference in mouse embryos. Development. 2005;132:2599-609 pubmed
    ..This functional genomic approach allows the rapid identification of functionally important components of embryonic development from large datasets of putative targets. ..
  20. Alvarez Medina R, Cayuso J, Okubo T, Takada S, Marti E. Wnt canonical pathway restricts graded Shh/Gli patterning activity through the regulation of Gli3 expression. Development. 2008;135:237-47 pubmed
    ..Here, we show that Wnt1/Wnt3a, by signalling through the canonical beta-catenin/Tcf pathway, control expression of dorsal genes and suppression ..
  21. Nam J, Turcotte T, Smith P, Choi S, Yoon J. Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression. J Biol Chem. 2006;281:13247-57 pubmed
    ..Our findings expand the repertoire of ligands that induce beta-catenin/TCF-dependent gene activation and implicate the presence of active beta-catenin-dependent gene activation in a Wnt-free biological context. ..
  22. Osakada F, Ooto S, Akagi T, Mandai M, Akaike A, Takahashi M. Wnt signaling promotes regeneration in the retina of adult mammals. J Neurosci. 2007;27:4210-9 pubmed
    ..b>Wnt3a treatment increases proliferation of dedifferentiated Müller glia >20-fold in the photoreceptor-damaged retina...
  23. Pinson K, Brennan J, Monkley S, Avery B, Skarnes W. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature. 2000;407:535-8 pubmed
    ..Furthermore, we show a genetic enhancement of a Wnt mutant phenotype in mice lacking one functional copy of LRP6. Together, our results support a broad role for LRP6 in the transduction of several Wnt signals in mammals. ..
  24. 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. ..
  25. Yokoyama N, Golebiewska U, Wang H, Malbon C. Wnt-dependent assembly of supermolecular Dishevelled-3-based complexes. J Cell Sci. 2010;123:3693-702 pubmed publisher
    ..4 to 2.0 MDa. Addition of Wnt3a stimulates the formation of Dvl3-based complexes of greater molecular mass within 30 minutes...
  26. Munji R, Choe Y, Li G, Siegenthaler J, Pleasure S. Wnt signaling regulates neuronal differentiation of cortical intermediate progenitors. J Neurosci. 2011;31:1676-87 pubmed publisher
    ..Upregulation of Wnt-?-catenin signaling by overexpression of Wnt3a in the neocortex induced early differentiation of IPs into neurons and the accumulation of these newly born ..
  27. Chapman D, Papaioannou V. Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6. Nature. 1998;391:695-7 pubmed
  28. Ikeya M, Takada S. Wnt-3a is required for somite specification along the anteroposterior axis of the mouse embryo and for regulation of cdx-1 expression. Mech Dev. 2001;103:27-33 pubmed
    ..These results indicate that Wnt-3a is necessary for correct anteroposterior patterning of vertebra, and that cdx-1 may be one of the mediator genes of Wnt-3a signaling in this process. ..
  29. Bilic J, Huang Y, Davidson G, Zimmermann T, Cruciat C, Bienz M, et al. Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation. Science. 2007;316:1619-22 pubmed
    ..We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and beta-catenin stabilization. ..
  30. Endo Y, Wolf V, Muraiso K, Kamijo K, Soon L, Uren A, et al. Wnt-3a-dependent cell motility involves RhoA activation and is specifically regulated by dishevelled-2. J Biol Chem. 2005;280:777-86 pubmed
    ..Specific knock-down of Dvl-2 expression markedly reduced Wnt-3a-dependent changes in cell shape and movement, suggesting that this Dvl isoform had a predominant role in mediating Wnt-3a-dependent motility in Chinese hamster ovary cells. ..
  31. Wittler L, Shin E, Grote P, Kispert A, Beckers A, Gossler A, et al. Expression of Msgn1 in the presomitic mesoderm is controlled by synergism of WNT signalling and Tbx6. EMBO Rep. 2007;8:784-9 pubmed
    ..These findings emphasize the crucial role of WNT signalling in the control of psm formation, maturation and segmentation. ..
  32. Wang J, Ruan N, Qian L, Lei W, Chen F, Luo Z. Wnt/beta-catenin signaling suppresses Rapsyn expression and inhibits acetylcholine receptor clustering at the neuromuscular junction. J Biol Chem. 2008;283:21668-75 pubmed publisher
    ..Here we report that Wnt3a negatively regulates acetylcholine receptor (AChR) clustering by repressing the expression of Rapsyn, an AChR-..
  33. Garel S, Huffman K, Rubenstein J. Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants. Development. 2003;130:1903-14 pubmed
    ..Overall, our study demonstrates the role of endogenous Fgf8 in regulating early gradients of transcription factors in cortical progenitor cells and in molecular regionalization of the cortical plate. ..
  34. 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. Wnt11 is highly expressed at the gastro-esophageal junctions, while Wnt4 is found in the epithelium lining the pyloric region of the stomach but not in the epithelium of the prospective gland region. ..
  35. 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
    ..paraxial mesoderm and lead to the formation of additional neural tubes, phenotypes identical to those reported for Wnt3a-deficient mice...
  36. 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. ..
  37. Biris K, Dunty W, Yamaguchi T. Mouse Ripply2 is downstream of Wnt3a and is dynamically expressed during somitogenesis. Dev Dyn. 2007;236:3167-72 pubmed
    ..Notch-centered segmentation clock, whereas boundaries are spatially positioned by the secreted signaling molecules Wnt3a and Fgf8...
  38. Roelink H, Nusse R. Expression of two members of the Wnt family during mouse development--restricted temporal and spatial patterns in the developing neural tube. Genes Dev. 1991;5:381-8 pubmed
    ..Characteristic expression patterns of these two closely related genes suggest that Wnt-3 and Wnt-3A play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube. ..
  39. Rawal N, Corti O, Sacchetti P, Ardilla Osorio H, Sehat B, Brice A, et al. Parkin protects dopaminergic neurons from excessive Wnt/beta-catenin signaling. Biochem Biophys Res Commun. 2009;388:473-8 pubmed publisher
    ..b>Wnt3a signaling also causes death of post-mitotic DA neurons in parkin null animals, suggesting that both increased ..
  40. Assimacopoulos S, Grove E, Ragsdale C. Identification of a Pax6-dependent epidermal growth factor family signaling source at the lateral edge of the embryonic cerebral cortex. J Neurosci. 2003;23:6399-403 pubmed
    ..We find that the antihem is lost in mice homozygous for the Small eye (Pax6) mutation and suggest the loss of EGF signaling at least partially explains defects in cortical patterning and cell migration in Small eye mice. ..
  41. 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. ..
  42. 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. ..
  43. Backman M, Machon O, Mygland L, van den Bout C, Zhong W, Taketo M, et al. Effects of canonical Wnt signaling on dorso-ventral specification of the mouse telencephalon. Dev Biol. 2005;279:155-68 pubmed
    ..Thus, our data suggest that canonical Wnt signals are involved in maintaining the identity of the pallium by controlling expression of dorsal markers and by suppressing ventral programs from being activated in pallial progenitor cells. ..
  44. Mangale V, Hirokawa K, Satyaki P, Gokulchandran N, Chikbire S, Subramanian L, et al. Lhx2 selector activity specifies cortical identity and suppresses hippocampal organizer fate. Science. 2008;319:304-9 pubmed publisher
    ..In addition to providing functional evidence for Lhx2 selector activity, these findings show that the cortical hem is a hippocampal organizer. ..
  45. Yoshida M, Assimacopoulos S, Jones K, Grove E. Massive loss of Cajal-Retzius cells does not disrupt neocortical layer order. Development. 2006;133:537-45 pubmed
    ..Our findings indicate, however, that the sheet of reelin-rich CR cells that covers the neocortical primordium is not required to direct layer order. ..
  46. Cambray N, Wilson V. Two distinct sources for a population of maturing axial progenitors. Development. 2007;134:2829-40 pubmed
    ..Therefore, at least some aspects of progenitor status are conferred by the environment and are not an intrinsic property of the cells...
  47. Lu W, Kim K, Liu J, Abo A, Feng X, Cao X, et al. R-spondin1 synergizes with Wnt3A in inducing osteoblast differentiation and osteoprotegerin expression. FEBS Lett. 2008;582:643-50 pubmed publisher
    ..We reported herein that R-sponin1 (Rspo1) acted synergistically with Wnt3A to activate Wnt/beta-catenin signaling in the uncommitted mesenchymal C2C12 cells...
  48. Bouillet P, Oulad Abdelghani M, Ward S, Bronner S, Chambon P, Dolle P. A new mouse member of the Wnt gene family, mWnt-8, is expressed during early embryogenesis and is ectopically induced by retinoic acid. Mech Dev. 1996;58:141-52 pubmed
    ..We also show that mWnt-8 expression is ectopically induced in the rostral neural plate in response to RA exposure of presumitic (7-7.5 days post coitum) cultured mouse embryos. ..
  49. Wisniewska M, Misztal K, Michowski W, Szczot M, Purta E, Lesniak W, et al. LEF1/beta-catenin complex regulates transcription of the Cav3.1 calcium channel gene (Cacna1g) in thalamic neurons of the adult brain. J Neurosci. 2010;30:4957-69 pubmed publisher
    ..of Cacna1g is high in the thalamus and is further increased in thalamic neurons treated in vitro with LiCl or WNT3A, activators of beta-catenin...
  50. Hanashima C, Fernandes M, Hebert J, Fishell G. The role of Foxg1 and dorsal midline signaling in the generation of Cajal-Retzius subtypes. J Neurosci. 2007;27:11103-11 pubmed
  51. Willert K, Brown J, Danenberg E, Duncan A, Weissman I, Reya T, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423:448-52 pubmed
    ..Here we have isolated active Wnt molecules, including the product of the mouse Wnt3a gene. By mass spectrometry, we found the proteins to be palmitoylated on a conserved cysteine...
  52. Satoh K, Kasai M, Ishidao T, Tago K, Ohwada S, Hasegawa Y, et al. Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor (ICAT), a negative regulator of Wnt signaling. Proc Natl Acad Sci U S A. 2004;101:8017-21 pubmed
    ..Analysis of the neuronal differentiation of embryonic stem cells revealed that Wnt3a redirects the fate of neural progenitors to a posterior character, whereas ICAT induces forebrain cells by ..
  53. Yoshikawa Y, Fujimori T, McMahon A, Takada S. Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse. Dev Biol. 1997;183:234-42 pubmed
    ..These results suggest that Wnt-3a signaling may play a role in regulating paraxial mesodermal fates, at the expense of neurectodermal fates, within the primitive ectoderm of the gastrulating mouse embryo. ..