Gene Symbol: Wnt2
Description: wingless-type MMTV integration site family, member 2
Alias: 2610510E18Rik, Int1l1, Irp, Mirp, Wnt-2, Wnt2a, protein Wnt-2, INT-1-related protein, wingless-related MMTV integration site 2
Species: mouse
Products:     Wnt2

Top Publications

  1. Bayle J, Fitch J, Jacobsen K, Kumar R, Lafyatis R, Lemaire R. Increased expression of Wnt2 and SFRP4 in Tsk mouse skin: role of Wnt signaling in altered dermal fibrillin deposition and systemic sclerosis. J Invest Dermatol. 2008;128:871-81 pubmed
    ..Tsk skin showed increased mRNA levels of several genes involved in Wnt signaling, including Wnt2, Wnt9a, Wnt10b and Wnt11; Dapper homolog antagonist of beta-catenin (DACT1) and DACT2; Wnt-induced secreted protein ..
  2. Zhang A, Shen C, Ma S, Ke Y, El Idrissi A. Altered expression of Autism-associated genes in the brain of Fragile X mouse model. Biochem Biophys Res Commun. 2009;379:920-3 pubmed publisher
    ..Genet. 142 (2006) 40-51]. We have used real-time PCR to investigate changes in expression levels of three genes: WNT2, MECP2, and FMR1 in different brain regions of Fagile X mice and litter mate controls...
  3. 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...
  4. Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, et al. Fgf10 is essential for limb and lung formation. Nat Genet. 1999;21:138-41 pubmed
    ..Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation. ..
  5. Pepicelli C, Lewis P, McMahon A. Sonic hedgehog regulates branching morphogenesis in the mammalian lung. Curr Biol. 1998;8:1083-6 pubmed
    ..In addition, the transcription of several mesenchymally expressed downstream targets of Shh is abolished. These results highlight the importance of epithelially derived Shh in regulating branching morphogenesis of the lung. ..
  6. Monkley S, Delaney S, Pennisi D, Christiansen J, Wainwright B. Targeted disruption of the Wnt2 gene results in placentation defects. Development. 1996;122:3343-53 pubmed
    ..Reported here for the first time is the expression of Wnt2 in the early heart field of 7.5-8...
  7. Tian Y, Yuan L, Goss A, Wang T, Yang J, Lepore J, et al. Characterization and in vivo pharmacological rescue of a Wnt2-Gata6 pathway required for cardiac inflow tract development. Dev Cell. 2010;18:275-87 pubmed publisher
    ..Here we show that Wnt2 is expressed specifically in the developing inflow tract mesoderm, which generates portions of the atria and atrio-..
  8. Harris Johnson K, Domyan E, Vezina C, Sun X. beta-Catenin promotes respiratory progenitor identity in mouse foregut. Proc Natl Acad Sci U S A. 2009;106:16287-92 pubmed publisher
    ..Our findings reveal an early role for beta-Catenin in the establishment of respiratory progenitors in mouse foregut endoderm. ..
  9. Goss A, Tian Y, Cheng L, Yang J, Zhou D, Cohen E, et al. Wnt2 signaling is necessary and sufficient to activate the airway smooth muscle program in the lung by regulating myocardin/Mrtf-B and Fgf10 expression. Dev Biol. 2011;356:541-52 pubmed publisher
    ..Here, we identify the Wnt2 ligand as a critical regulator of the earliest aspects of lung airway smooth muscle development...

More Information


  1. Goss A, Tian Y, Tsukiyama T, Cohen E, Zhou D, Lu M, et al. Wnt2/2b and beta-catenin signaling are necessary and sufficient to specify lung progenitors in the foregut. Dev Cell. 2009;17:290-8 pubmed publisher
    ..However, the molecular pathways specifying foregut endoderm progenitors are poorly understood. We show here that Wnt2/2b signaling is required to specify lung endoderm progenitors within the anterior foregut...
  2. Weidenfeld J, Shu W, Zhang L, Millar S, Morrisey E. The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium. J Biol Chem. 2002;277:21061-70 pubmed
    ..Together, these results suggest that WNT7b gene expression in the lung epithelium is regulated in a combinatorial fashion by TTF-1, GATA6, and Foxa2. ..
  3. Wang H, Li T, Kidder G. WNT2 regulates DNA synthesis in mouse granulosa cells through beta-catenin. Biol Reprod. 2010;82:865-75 pubmed publisher
    ..Therefore, the objective of this study was to investigate the regulation and function of WNT2 signaling in mouse granulosa cells...
  4. Bühler T, Dale T, Kieback C, Humphreys R, Rosen J. Localization and quantification of Wnt-2 gene expression in mouse mammary development. Dev Biol. 1993;155:87-96 pubmed
    ..Furthermore, they suggest that Wnt-2, as well as several other family members, may play a role in pattern formation during early mammary gland development. ..
  5. Kaestner K, Silberg D, Traber P, Schutz G. The mesenchymal winged helix transcription factor Fkh6 is required for the control of gastrointestinal proliferation and differentiation. Genes Dev. 1997;11:1583-95 pubmed
  6. Chan A, Hilkens J, Kroezen V, Mitchell P, Scambler P, Wainwright B, et al. Molecular cloning and localization to chromosome 6 of mouse INT1L1 gene. Somat Cell Mol Genet. 1989;15:555-62 pubmed
    The human INT1L1 gene, which exhibits homology to the protooncogene INT1 is very closely linked to the MET gene and cystic fibrosis locus on human chromosome 7...
  7. Zhang X, Ramalho Santos M, McMahon A. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node. Cell. 2001;106:781-92 pubmed
    ..Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis. ..
  8. Bazzi H, Fantauzzo K, Richardson G, Jahoda C, Christiano A. The Wnt inhibitor, Dickkopf 4, is induced by canonical Wnt signaling during ectodermal appendage morphogenesis. Dev Biol. 2007;305:498-507 pubmed
    ..We propose that Dkk4 acts in a negative feedback loop to attenuate canonical Wnt signaling, and may facilitate a switch to the non-canonical Wnt planar cell polarity (PCP) pathway that is involved in cell movements during morphogenesis. ..
  9. Okubo T, Hogan B. Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm. J Biol. 2004;3:11 pubmed
    ..We discuss the relevance of our findings to the poorly understood pathological condition of intestinal metaplasia in humans. ..
  10. Zhang X, Ramalho Santos M, McMahon A. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node. Cell. 2001;105:781-92 pubmed
    ..Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis.[Dedicated to Rosa Beddington, a pioneer in mammalian embryology]. ..
  11. Zhang Y, Goss A, Cohen E, Kadzik R, Lepore J, Muthukumaraswamy K, et al. A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration. Nat Genet. 2008;40:862-70 pubmed publisher
    ..Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration. ..
  12. He F, Xiong W, Wang Y, Li L, Liu C, Yamagami T, et al. Epithelial Wnt/?-catenin signaling regulates palatal shelf fusion through regulation of Tgf?3 expression. Dev Biol. 2011;350:511-9 pubmed publisher
    ..Collectively, our results demonstrate an essential role for Wnt/?-catenin signaling in the epithelial component at the step of palate fusion during palate development by controlling the expression of Tgf?3 in the MEE. ..
  13. Kimura M, Nakajima Koyama M, Lee J, Nishida E. Transient Expression of WNT2 Promotes Somatic Cell Reprogramming by Inducing ?-Catenin Nuclear Accumulation. Stem Cell Reports. 2016;6:834-843 pubmed publisher
    ..Here we identify the upregulation of WNT2 and subsequent ?-catenin nuclear accumulation as key events in reprogramming...
  14. Yi L, Domyan E, Lewandoski M, Sun X. Fibroblast growth factor 9 signaling inhibits airway smooth muscle differentiation in mouse lung. Dev Dyn. 2009;238:123-37 pubmed publisher
    ..This model also represents our findings on the genetic relationship between FGF9 and sonic hedgehog (SHH) in the establishment of airway SMC pattern. ..
  15. 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. ..
  16. Knosp W, Knox S, Lombaert I, Haddox C, Patel V, Hoffman M. Submandibular parasympathetic gangliogenesis requires sprouty-dependent Wnt signals from epithelial progenitors. Dev Cell. 2015;32:667-77 pubmed publisher
    ..Thus, K5+ progenitors produce Wnt signals to establish the PSG-epithelial communication required for organ innervation and progenitor cell maintenance. ..
  17. Yamaguchi Y, Ogura S, Ishida M, Karasawa M, Takada S. Gene trap screening as an effective approach for identification of Wnt-responsive genes in the mouse embryo. Dev Dyn. 2005;233:484-95 pubmed
    ..These results indicate that the gene trap is an effective method for systematic identification of Wnt-responsive genes during embryogenesis. ..
  18. Alexandrovich A, Arno M, Patient R, Shah A, Pizzey J, Brewer A. Wnt2 is a direct downstream target of GATA6 during early cardiogenesis. Mech Dev. 2006;123:297-311 pubmed
    ..We show that early cardiac expression of one of these genes, Wnt2, mirrors that of GATA6 in vitro and in vivo...
  19. Hiester B, Galati D, Salinas P, Jones K. Neurotrophin and Wnt signaling cooperatively regulate dendritic spine formation. Mol Cell Neurosci. 2013;56:115-27 pubmed publisher
    ..Additionally, we show that BDNF regulates expression of Wnt2, and that Wnt2 is sufficient to promote cortical dendrite growth and dendritic spine formation...
  20. Sgantzis N, Yiakouvaki A, Remboutsika E, Kontoyiannis D. HuR controls lung branching morphogenesis and mesenchymal FGF networks. Dev Biol. 2011;354:267-79 pubmed publisher
    ..Our data reveals HuR as the first RBP identified to play a dominant role in lung development and as a key post-transcriptional regulator of networks guiding tissue remodeling during branching morphogenesis. ..
  21. Liu H, Mohamed O, Dufort D, Wallace V. Characterization of Wnt signaling components and activation of the Wnt canonical pathway in the murine retina. Dev Dyn. 2003;227:323-34 pubmed
  22. Loureiro J. The Wnts. Curr Biol. 1999;9:R4 pubmed
  23. Yin Y, Castro A, Hoekstra M, Yan T, Kanakamedala A, Dehner L, et al. Fibroblast Growth Factor 9 Regulation by MicroRNAs Controls Lung Development and Links DICER1 Loss to the Pathogenesis of Pleuropulmonary Blastoma. PLoS Genet. 2015;11:e1005242 pubmed publisher
    ..These studies identify an essential miRNA-FGF9 pathway for lung development and a non-cell autonomous signaling mechanism that contributes to the mesenchymal hyperplasia that is characteristic of Type I PPB. ..
  24. Zhang K, Xiang M, Zhou L, Liu J, Curry N, Heine Suñer D, et al. Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation. Hum Mol Genet. 2016;25:1140-51 pubmed publisher
    ..In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in SHF for atrial septation, providing a molecular framework for understanding the role of Tbx5 in CHD ontogeny. ..
  25. Sousa K, Villaescusa J, Cajanek L, Ondr J, Castelo Branco G, Hofstra W, et al. Wnt2 regulates progenitor proliferation in the developing ventral midbrain. J Biol Chem. 2010;285:7246-53 pubmed publisher
    ..In this study, we perform the first purification and signaling analysis of Wnt2 and define the function of Wnt2 in ventral midbrain precursor cultures, as well as in Wnt2-null mice in vivo...
  26. Yu X, Wang Y, Jiang M, Bierie B, Roy Burman P, Shen M, et al. Activation of beta-Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration. Prostate. 2009;69:249-62 pubmed publisher
  27. Rawnsley D, Xiao J, Lee J, Liu X, Mericko Ishizuka P, Kumar V, et al. The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development. J Biol Chem. 2013;288:24429-40 pubmed publisher
    ..Whether ATOH8 modulates GATA-FOG function at other sites or in more subtle ways in mammals is not yet known...
  28. Nishimoto S, Wilde S, Wood S, Logan M. RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation. Cell Rep. 2015;12:879-91 pubmed publisher
    ..Our results incorporate RA-, β-catenin/TCF/LEF-, and FGF-signaling pathways into a regulatory network acting to recruit cells of the embryo flank to become limb precursors. ..
  29. Caprioli A, Villasenor A, Wylie L, Braitsch C, Marty Santos L, Barry D, et al. Wnt4 is essential to normal mammalian lung development. Dev Biol. 2015;406:222-34 pubmed publisher
    ..In addition, we observe reduction of the important lung growth factors Fgf9, Fgf10, Sox9 and Wnt2 in the lung bud during early stages of organogenesis, as well as decreased tracheal expression of the progenitor ..
  30. da Silva F, Rocha A, Motamedi F, Massa F, Basboga C, Morrison H, et al. Coronary Artery Formation Is Driven by Localized Expression of R-spondin3. Cell Rep. 2017;20:1745-1754 pubmed publisher
    ..These results identify a mechanism through which localized expression of RSPO3 induces proliferation of the coronary arteries at their stems and permits their formation. ..
  31. Salazar K, Lankford S, Brody A. Mesenchymal stem cells produce Wnt isoforms and TGF-beta1 that mediate proliferation and procollagen expression by lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2009;297:L1002-11 pubmed publisher
    ..In addition, anti-Wnt1 and anti-Wnt2 antibodies attenuated MSC-CM-induced proliferation, and increased expression of Wnt7b was identified...
  32. Gavin B, McMahon J, McMahon A. Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development. Genes Dev. 1990;4:2319-32 pubmed
    ..All new Wnt family members are expressed in adult tissues, particularly in brain and lung. These data support the view that the Wnt-1/int-1 family constitutes a large family of signaling peptides with diverse roles in mouse development. ..
  33. Chua S, Hennessey K, Zeitler P, Leibel R. The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse chromosome 6. Mamm Genome. 1993;4:555-9 pubmed
    ..Low level of message could reflect a primary molecular defect or be due to secondary hypoplasia of somatotropes.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  34. Bellusci S, Henderson R, Winnier G, Oikawa T, Hogan B. Evidence from normal expression and targeted misexpression that bone morphogenetic protein (Bmp-4) plays a role in mouse embryonic lung morphogenesis. Development. 1996;122:1693-702 pubmed
    ..A model is proposed for the role of BMP4 and other signalling molecules in embryonic lung morphogenesis. ..
  35. Alfieri C, Cheek J, Chakraborty S, Yutzey K. Wnt signaling in heart valve development and osteogenic gene induction. Dev Biol. 2010;338:127-35 pubmed publisher
    ..Multiple Wnt ligands and pathway genes are differentially expressed during heart valve development. At E12.5, Wnt2 is expressed in cushion mesenchyme, whereas Wnt4 and Wnt9b are predominant in overlying endothelial cells. At E17...
  36. Wainwright B, Scambler P, Stanier P, Watson E, Bell G, Wicking C, et al. Isolation of a human gene with protein sequence similarity to human and murine int-1 and the Drosophila segment polarity mutant wingless. EMBO J. 1988;7:1743-8 pubmed
    ..This human int-1 related protein, int-1 and Dint-1 have diverse patterns of expression, but the inferred structural similarities suggest that some of the functional characteristics of these proteins may be shared. ..
  37. Davies P, Melanitou E, Asano M, Avner P, Montagutelli X. An anchored molecular map of mouse chromosome 6 with an analysis of interference. Mamm Genome. 1995;6:738-40 pubmed
  38. Lickert H, Kispert A, Kutsch S, Kemler R. Expression patterns of Wnt genes in mouse gut development. Mech Dev. 2001;105:181-4 pubmed
    ..Here we describe the identification of Wnt genes, Wnt2a, 4, 5a, 5b, 6 and 11, expressed in mouse embryonic gut development...
  39. Verani R, Cappuccio I, Spinsanti P, Gradini R, Caruso A, Magnotti M, et al. Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid. J Neurochem. 2007;100:242-50 pubmed
    ..These data suggest that induction of Dkk-1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells. ..
  40. Lu J, Zhang S, Nakano H, Simmons D, Wang S, Kong S, et al. A positive feedback loop involving Gcm1 and Fzd5 directs chorionic branching morphogenesis in the placenta. PLoS Biol. 2013;11:e1001536 pubmed publisher
    ..These data indicate that Gcm1 and Fzd5 function in an evolutionary conserved positive feedback loop that regulates trophoblast differentiation and sites of chorionic branching morphogenesis...
  41. Peng T, Tian Y, Boogerd C, Lu M, Kadzik R, Stewart K, et al. Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor. Nature. 2013;500:589-92 pubmed publisher
    ..mesoderm progenitors (CPPs) within the posterior pole of the heart that are marked by the expression of Wnt2, Gli1 and Isl1. We show that CPPs arise from cardiac progenitors before lung development...
  42. 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. ..
  43. Snowball J, Ambalavanan M, Whitsett J, Sinner D. Endodermal Wnt signaling is required for tracheal cartilage formation. Dev Biol. 2015;405:56-70 pubmed publisher
    ..In conclusion, Wnt ligands produced by the tracheal epithelium pattern the tracheal mesenchyme via modulation of gene expression and cell proliferation required for proper tracheal cartilage and smooth muscle differentiation. ..
  44. Zhang Y, Singh M, Degenhardt K, Lu M, Bennett J, Yoshida Y, et al. Tie2Cre-mediated inactivation of plexinD1 results in congenital heart, vascular and skeletal defects. Dev Biol. 2009;325:82-93 pubmed publisher
    ..These results demonstrate an important role for PlexinD1 in embryonic and adult vasculature. ..
  45. Williams H, Mill C, Monk B, Hulin Curtis S, Johnson J, George S. Wnt2 and WISP-1/CCN4 Induce Intimal Thickening via Promotion of Smooth Muscle Cell Migration. Arterioscler Thromb Vasc Biol. 2016;36:1417-24 pubmed publisher
    ..In this study, we determined whether Wnt proteins regulate VSMC migration and thereby intimal thickening. Wnt2 mRNA and protein expression were specifically increased in migrating mouse aortic VSMCs...
  46. Yao C, Carraro G, Konda B, Guan X, Mizuno T, Chiba N, et al. Sin3a regulates epithelial progenitor cell fate during lung development. Development. 2017;144:2618-2628 pubmed publisher
    ..Together, these findings reveal that Sin3a is an essential regulator for early lung endoderm specification and differentiation. ..
  47. Uusitalo M, Heikkilä M, Vainio S. Molecular genetic studies of Wnt signaling in the mouse. Exp Cell Res. 1999;253:336-48 pubmed
  48. Costello I, Pimeisl I, Dräger S, Bikoff E, Robertson E, Arnold S. The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation. Nat Cell Biol. 2011;13:1084-91 pubmed publisher
    ..Collectively, our experiments demonstrate that Eomes governs discrete context-dependent transcriptional programmes that sequentially specify cardiac and definitive endoderm progenitors during gastrulation. ..
  49. 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. ..
  50. Han L, Xu J, Grigg E, Slack M, Chaturvedi P, Jiang R, et al. Osr1 functions downstream of Hedgehog pathway to regulate foregut development. Dev Biol. 2017;427:72-83 pubmed publisher
    ..We conclude that Osr1 is a novel downstream target of HH pathway, required for lung specification, branching morphogenesis and foregut mesenchymal differentiation. ..
  51. Yu H, He K, Li L, Sun L, Tang F, Li R, et al. Deletion of STK40 protein in mice causes respiratory failure and death at birth. J Biol Chem. 2013;288:5342-52 pubmed publisher
    ..STK40 may associate with RCN2 to activate ERK/MAPK signaling and control the expression of multiple key regulators of lung development. ..
  52. Nusse R, Brown A, Papkoff J, Scambler P, Shackleford G, McMahon A, et al. A new nomenclature for int-1 and related genes: the Wnt gene family. Cell. 1991;64:231 pubmed
  53. Mohamed O, Dufort D, Clarke H. Expression and estradiol regulation of Wnt genes in the mouse blastocyst identify a candidate pathway for embryo-maternal signaling at implantation. Biol Reprod. 2004;71:417-24 pubmed