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Encyclopedia of Signaling Molecules pp 5998–6004Cite as

WNT

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Synonyms

Wingless-related integration site; Wingless-type MMTV integration site family

Historical Background

Wnt is a primordial signaling pathway, which is conserved from lower invertebrates to higher vertebrates and mammal (Chen et al. 2008). The founders of this pathway were discovered in the late 1900s in fruit flies and in mouse mammary cancers (Lerner and Ohlsson 2015) The name “Wnt” originated from a combination of wingless (Wg) and integrase1 (Int1). The Int1 gene is an oncogene, while Wg is a developmental gene in drosophila which is homologous to Int1 (Nusse and Varmus 1982; Rijsewijk et al. 1987).

Wnt Proteins Structure

Wnts are secreted glycolipoproteins, which are approximately 350 amino acids long, 40 kDa in molecular weight, and contain several charged cysteine residues (approx. 23–25) (Farin et al. 2016). These cysteine residues mediate Wnt folding and multimerization by regulating the formation of intermolecular and intramolecular disulfide bond (Janda et al. 2012)....

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References

  • Bazan JF, de Sauvage FJ. Structural ties between cholesterol transport and morphogen signaling. Cell. 2009;138:1055–6.

    Article  PubMed  CAS  Google Scholar 

  • Biason-Lauber A, Konrad D. WNT4 and sex development. Sex Dev. 2008;2:210–8.

    Article  PubMed  CAS  Google Scholar 

  • Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ. A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46 XX woman. N Engl J Med. 2004;351:792–8.

    Article  PubMed  CAS  Google Scholar 

  • Bradley EW, Drissi MH. Wnt5b regulates mesenchymal cell aggregation and chondrocyte differentiation through the planar cell polarity pathway. J Cell Physiol. 2011;226:1683–93.

    Article  PubMed  CAS  Google Scholar 

  • Brisken C, Heineman A, Chavarria T, Elenbaas B, Tan J, Dey SK, et al. Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev. 2000;14:650–4.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP. Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell. 2005;9:283–92.

    Article  PubMed  CAS  Google Scholar 

  • Cervantes S, Yamaguchi TP, Hebrok M. Wnt5a is essential for intestinal elongation in mice. Dev Biol. 2009;326:285–94.

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Yang J, Evans PM, Liu C. Wnt signaling: the good and the bad. Acta Biochim Biophys Sin Shanghai. 2008;40:577–94.

    Article  PubMed  CAS  Google Scholar 

  • Cohen ED, Tian Y, Morrisey EE. Wnt signaling: an essential regulator of cardiovascular differentiation, morphogenesis and progenitor self-renewal. Development. 2008;135:789–98.

    Article  PubMed  CAS  Google Scholar 

  • Cunningham TJ, Kumar S, Yamaguchi TP, Duester G. Wnt8a and Wnt3a cooperate in the axial stem cell niche to promote mammalian body axis extension. Dev Dyn. 2015;244:797–807.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Das S, Yu S, Sakamori R, Stypulkowski E, Gao N. Wntless in Wnt secretion: molecular, cellular and genetic aspects. Front Biol (Beijing). 2012;7:587–93.

    Article  CAS  Google Scholar 

  • Farin HF, Jordens I, Mosa MH, Basak O, Korving J, Tauriello DV, et al. Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature. 2016;530:340–3.

    Article  PubMed  CAS  Google Scholar 

  • Gavin BJ, McMahon JA, McMahon AP. Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development. Genes Dev. 1990;4:2319–32.

    Article  PubMed  CAS  Google Scholar 

  • Gori F, Lerner U, Ohlsson C, Baron R. A new WNT on the bone: WNT16, cortical bone thickness, porosity and fractures. Bonekey Rep. 2015;4:669.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Greco TL, Takada S, Newhouse MM, McMahon JA, McMahon AP, Camper SA. Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development. Genes Dev. 1996;10:313–24.

    Article  PubMed  CAS  Google Scholar 

  • Hall AC, Lucas FR, Salinas PC. Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell. 2000;100:525–35.

    Article  PubMed  CAS  Google Scholar 

  • Hasenpusch-Theil K, Watson JA, Theil T. Direct interactions between Gli3, Wnt8b, and Fgfs underlie patterning of the dorsal telencephalon. Cereb Cortex. 2017;27:1137–48.

    Google Scholar 

  • Hu B, Lefort K, Qiu W, Nguyen BC, Rajaram RD, 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ikeya M, Lee SM, Johnson JE, McMahon AP, Takada S. Wnt signalling required for expansion of neural crest and CNS progenitors. Nature. 1997;389:966–70.

    Article  PubMed  CAS  Google Scholar 

  • Janda CY, Waghray D, Levin AM, Thomas C, Garcia KC. Structural basis of Wnt recognition by frizzled. Science. 2012;337:59–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jin YR, Han XH, Taketo MM, Yoon JK. Wnt9b-dependent FGF signaling is crucial for outgrowth of the nasal and maxillary processes during upper jaw and lip development. Development. 2012;139:1821–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Karner CM, Das A, Ma Z, Self M, Chen C, Lum L, et al. Canonical Wnt9b signaling balances progenitor cell expansion and differentiation during kidney development. Development. 2011;138:1247–57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kemp C, Willems E, Abdo S, Lambiv L, Leyns L. Expression of all Wnt genes and their secreted antagonists during mouse blastocyst and postimplantation development. Dev Dyn. 2005;233:1064–75.

    Article  CAS  PubMed  Google Scholar 

  • Lavery DL, Martin J, Turnbull YD, Hoppler S. Wnt6 signaling regulates heart muscle development during organogenesis. Dev Biol. 2008;323:177–88.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lerner UH, Ohlsson C. The WNT system: background and its role in bone. J Intern Med. 2015;277:630–49.

    Article  CAS  PubMed  Google Scholar 

  • Li C, Xiao J, Hormi K, Borok Z, Minoo P. Wnt5a participates in distal lung morphogenesis. Dev Biol. 2002;248:68–81.

    Article  CAS  PubMed  Google Scholar 

  • Li L, Hutchins BI, Kalil K. Wnt5a induces simultaneous cortical axon outgrowth and repulsive axon guidance through distinct signaling mechanisms. J Neurosci. 2009;29:5873–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lickert H, Kispert A, Kutsch S, Kemler R. Expression patterns of Wnt genes in mouse gut development. Mech Dev. 2001;105:181–4.

    Article  PubMed  CAS  Google Scholar 

  • Liu CF, Parker K, Yao HH. WNT4/beta-catenin pathway maintains female germ cell survival by inhibiting activin betaB in the mouse fetal ovary. PLoS One. 2010;5:e10382.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu P, Wakamiya M, Shea MJ, Albrecht U, Behringer RR, Bradley A. Requirement for Wnt3 in vertebrate axis formation. Nat Genet. 1999;22:361–5.

    Article  PubMed  CAS  Google Scholar 

  • Malinauskas T, Aricescu AR, Lu W, Siebold C, Jones EY. Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1. Nat Struct Mol Biol. 2011;18:886–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mandel H, Shemer R, Borochowitz ZU, Okopnik M, Knopf C, Indelman M, et al. SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet. 2008;82:39–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mastick GS, Fan CM, Tessier-Lavigne M, Serbedzija GN, McMahon AP, Easter Jr SS. Early deletion of neuromeres in Wnt-1−/− mutant mice: evaluation by morphological and molecular markers. J Comp Neurol. 1996;374:246–58.

    Article  PubMed  CAS  Google Scholar 

  • McMahon AP, Bradley A. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell. 1990;62:1073–85.

    Article  PubMed  CAS  Google Scholar 

  • Millar SE, Willert K, Salinas PC, Roelink H, Nusse R, Sussman DJ, et al. WNT signaling in the control of hair growth and structure. Dev Biol. 1999;207:133–49.

    Article  PubMed  CAS  Google Scholar 

  • Miller C, Sassoon DA. Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract. Development. 1998;125:3201–11.

    PubMed  CAS  Google Scholar 

  • Monkley SJ, Delaney SJ, Pennisi DJ, Christiansen JH, Wainwright BJ. Targeted disruption of the Wnt2 gene results in placentation defects. Development. 1996;122:3343–53.

    PubMed  CAS  Google Scholar 

  • Nagy II, Railo A, Rapila R, Hast T, Sormunen R, Tavi P, et al. Wnt-11 signalling controls ventricular myocardium development by patterning N-cadherin and beta-catenin expression. Cardiovasc Res. 2010;85:100–9.

    Article  CAS  PubMed  Google Scholar 

  • Nagy II, Xu Q, Naillat F, Ali N, Miinalainen I, Samoylenko A, et al. Impairment of Wnt11 function leads to kidney tubular abnormalities and secondary glomerular cystogenesis. BMC Dev Biol. 2016;16:30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Narayanan A, Thompson SA, Lee JJ, Lekven AC. A transgenic wnt8a:PAC reporter reveals biphasic regulation of vertebrate mesoderm development. Dev Dyn. 2011;240:898–907.

    Article  PubMed  CAS  Google Scholar 

  • Nusse R, Varmus H. Three decades of Wnts: a personal perspective on how a scientific field developed. EMBO J. 2012;31:2670–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982;31:99–109.

    Article  PubMed  CAS  Google Scholar 

  • Parr BA, Avery EJ, Cygan JA, McMahon AP. The classical mouse mutant postaxial hemimelia results from a mutation in the Wnt 7a gene. Dev Biol. 1998;202:228–34.

    Article  PubMed  CAS  Google Scholar 

  • Parr BA, Cornish VA, Cybulsky MI, McMahon AP. Wnt7b regulates placental development in mice. Dev Biol. 2001;237:324–32.

    Article  PubMed  CAS  Google Scholar 

  • Parr BA, McMahon AP. Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. Nature. 1995;374:350–3.

    Article  PubMed  CAS  Google Scholar 

  • Person AD, Garriock RJ, Krieg PA, Runyan RB, Klewer SE. Frzb modulates Wnt-9a-mediated beta-catenin signaling during avian atrioventricular cardiac cushion development. Dev Biol. 2005;278:35–48.

    Article  PubMed  CAS  Google Scholar 

  • Petropoulos H, Skerjanc IS. Beta-catenin is essential and sufficient for skeletal myogenesis in P19 cells. J Biol Chem. 2002;277:15393–9.

    Article  PubMed  CAS  Google Scholar 

  • Rijsewijk F, Schuermann M, Wagenaar E, Parren P, Weigel D, Nusse R. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless. Cell. 1987;50:649–57.

    Article  PubMed  CAS  Google Scholar 

  • Roker LA, Nemri K, Yu J. Wnt7b signaling from the ureteric bud epithelium regulates medullary capillary development. J Am Soc Nephrol. 2016. https://doi.org/10.1681/ASN.2015111205.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000;289:950–3.

    Article  PubMed  CAS  Google Scholar 

  • Schleiffarth JR, Person AD, Martinsen BJ, Sukovich DJ, Neumann A, Baker CV, et al. Wnt5a is required for cardiac outflow tract septation in mice. Pediatr Res. 2007;61:386–91.

    Article  PubMed  Google Scholar 

  • Sinha T, Li D, Theveniau-Ruissy M, Hutson MR, Kelly RG, Wang J. Loss of Wnt5a disrupts second heart field cell deployment and may contribute to OFT malformations in DiGeorge syndrome. Hum Mol Genet. 2015;24:1704–16.

    Article  PubMed  CAS  Google Scholar 

  • Spater D, Hill TP, O’Sullivan RJ, Gruber M, Conner DA, Hartmann C. Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis. Development. 2006;133:3039–49.

    Article  PubMed  CAS  Google Scholar 

  • Stark K, Vainio S, Vassileva G, McMahon AP. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature. 1994;372:679–83.

    Article  PubMed  CAS  Google Scholar 

  • Takada R, Satomi Y, Kurata T, Ueno N, Norioka S, Kondoh H, et al. Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Dev Cell. 2006;11:791–801.

    Article  PubMed  CAS  Google Scholar 

  • Takada S, Stark KL, Shea MJ, Vassileva G, McMahon JA, McMahon AP. Wnt-3a regulates somite and tailbud formation in the mouse embryo. Genes Dev. 1994;8:174–89.

    Article  PubMed  CAS  Google Scholar 

  • Trowbridge JJ, Guezguez B, Moon RT, Bhatia M. Wnt3a activates dormant c-Kit(-) bone marrow-derived cells with short-term multilineage hematopoietic reconstitution capacity. Stem Cells. 2010;28:1379–89.

    Article  PubMed  CAS  Google Scholar 

  • Tsukiyama T, Yamaguchi TP. Mice lacking Wnt2b are viable and display a postnatal olfactory bulb phenotype. Neurosci Lett. 2012;512:48–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vainio S, Heikkila M, Kispert A, Chin N, McMahon AP. Female development in mammals is regulated by Wnt-4 signalling. Nature. 1999;397:405–9.

    Article  PubMed  CAS  Google Scholar 

  • van Tienen FH, Laeremans H, van der Kallen CJ, Smeets HJ. Wnt5b stimulates adipogenesis by activating PPARgamma, and inhibiting the beta-catenin dependent Wnt signaling pathway together with Wnt5a. Biochem Biophys Res Commun. 2009;387:207–11.

    Article  PubMed  CAS  Google Scholar 

  • Vendrell V, Vazquez-Echeverria C, Lopez-Hernandez I, Alonso BD, Martinez S, Pujades C, et al. Roles of Wnt8a during formation and patterning of the mouse inner ear. Mech Dev. 2013;130:160–8.

    Article  PubMed  CAS  Google Scholar 

  • Vertino AM, Taylor-Jones JM, Longo KA, Bearden ED, Lane TF, McGehee Jr RE, et al. Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts. Mol Biol Cell. 2005;16:2039–48.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang C, Ren L, Peng L, Xu P, Dong G, Ye L. Effect of Wnt6 on human dental papilla cells in vitro. J Endod. 2010;36:238–43.

    Article  PubMed  Google Scholar 

  • Waschk DE, Tewes AC, Romer T, Hucke J, Kapczuk K, Schippert C, et al. Mutations in WNT9B are associated with Mayer-Rokitansky-Kuster-Hauser syndrome. Clin Genet. 2016;89:590–6.

    Article  PubMed  CAS  Google Scholar 

  • Wayman GA, Impey S, Marks D, Saneyoshi T, Grant WF, Derkach V, et al. Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron. 2006;50:897–909.

    Article  PubMed  CAS  Google Scholar 

  • Wergedal JE, Kesavan C, Brommage R, Das S, Mohan S. Role of WNT16 in the regulation of periosteal bone formation in female mice. Endocrinology. 2015;156:1023–32.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi TP, Bradley A, McMahon AP, Jones S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development. 1999a;126:1211–23.

    PubMed  CAS  Google Scholar 

  • Yamaguchi TP, Takada S, Yoshikawa Y, Wu N, McMahon AP. T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification. Genes Dev. 1999b;13:3185–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yoshikawa Y, Fujimori T, McMahon AP, 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.

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Huang Y, Cao X, Xu J, Zhang L, Wang J, et al. WNT2 promotes cervical carcinoma metastasis and induction of epithelial-mesenchymal transition. PLoS One. 2016;11:e0160414.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhavan, 31 MG Marg, Lucknow, 226001, India

    Anuradha Yadav & Rajnish Kumar Chaturvedi

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  1. Anuradha Yadav
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  2. Rajnish Kumar Chaturvedi
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Correspondence to Rajnish Kumar Chaturvedi .

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  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

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Yadav, A., Chaturvedi, R.K. (2018). WNT. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101790

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