Gene Symbol: WNT4
Description: Wnt family member 4
Alias: SERKAL, WNT-4, protein Wnt-4, wingless-type MMTV integration site family, member 4
Species: human
Products:     WNT4

Top Publications

  1. Vainio S, Heikkilä M, Kispert A, Chin N, McMahon A. Female development in mammals is regulated by Wnt-4 signalling. Nature. 1999;397:405-9 pubmed
    ..Wnt-4 may also be required for maintenance of the female germ line. Thus, the establishment of sexual dimorphism is under the control of both local and systemic signals. ..
  2. Lyons J, Mueller U, Ji H, Everett C, Fang X, Hsieh J, et al. Wnt-4 activates the canonical beta-catenin-mediated Wnt pathway and binds Frizzled-6 CRD: functional implications of Wnt/beta-catenin activity in kidney epithelial cells. Exp Cell Res. 2004;298:369-87 pubmed
  3. Uno S, Zembutsu H, Hirasawa A, Takahashi A, Kubo M, Akahane T, et al. A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. Nat Genet. 2010;42:707-10 pubmed publisher
    ..A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, ..
  4. Huguet E, McMahon J, McMahon A, Bicknell R, Harris A. 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. Cancer Res. 1994;54:2615-21 pubmed
    ..We report the expression of Wnt3, Wnt4, and Wnt7b in human breast cell lines and Wnt2, Wnt3, Wnt4, and Wnt7b in human breast tissues...
  5. Taki M, Kamata N, Yokoyama K, Fujimoto R, Tsutsumi S, Nagayama M. Down-regulation of Wnt-4 and up-regulation of Wnt-5a expression by epithelial-mesenchymal transition in human squamous carcinoma cells. Cancer Sci. 2003;94:593-7 pubmed
    ..These results indicated that Wnt-4 and Wnt-5a are oppositely affected by EMT, and down-regulation of Wnt-4 and up-regulation of Wnt-5a are possible markers of the malignant phenotype of human SCC. ..
  6. Jordan B, Shen J, Olaso R, Ingraham H, Vilain E. Wnt4 overexpression disrupts normal testicular vasculature and inhibits testosterone synthesis by repressing steroidogenic factor 1/beta-catenin synergy. Proc Natl Acad Sci U S A. 2003;100:10866-71 pubmed
    Genetic studies in mice suggest that Wnt4 signaling antagonizes expression of male hormones and effectively blocks male development in the female embryo...
  7. Torban E, Dziarmaga A, Iglesias D, Chu L, Vassilieva T, Little M, et al. PAX2 activates WNT4 expression during mammalian kidney development. J Biol Chem. 2006;281:12705-12 pubmed
    ..In this study we hypothesized that PAX2 activates expression of WNT4, a secreted glycoprotein known to be critical for successful nephrogenesis...
  8. Biason Lauber A, de Filippo G, Konrad D, Scarano G, Nazzaro A, Schoenle E. WNT4 deficiency--a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report. Hum Reprod. 2007;22:224-9 pubmed
    ..Loss-of-function mutations in the WNT4 gene appear to cause developmental abnormalities of sexual differentiation in women and mice...
  9. Mandel H, Shemer R, Borochowitz Z, 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 pubmed publisher
    ..Using a candidate-gene approach, we identified a disease-causing homozygous missense mutation in the human WNT4 gene...

More Information

Publications110 found, 100 shown here

  1. Memarian A, Hojjat Farsangi M, Asgarian Omran H, Younesi V, Jeddi Tehrani M, Sharifian R, et al. Variation in WNT genes expression in different subtypes of chronic lymphocytic leukemia. Leuk Lymphoma. 2009;50:2061-70 pubmed publisher
    ..Our results indicate up-regulation of many members of the WNT gene family in CLL suggesting involvement of the Wnt canonical and/or noncanonical signaling pathways in CLL tumorigenesis. ..
  2. Wan X, Ji W, Mei X, Zhou J, Liu J, Fang C, et al. Negative feedback regulation of Wnt4 signaling by EAF1 and EAF2/U19. PLoS ONE. 2010;5:e9118 pubmed publisher
    ..At the same time, EAF2/U19 is a downstream factor in the non-canonical Wnt 4 signaling pathway required for eye development in Xenopus laevis, and along with EAF1, contributes to convergence ..
  3. Osada M, Park H, Nagakawa Y, Begum S, Yamashita K, Wu G, et al. A novel response element confers p63- and p73-specific activation of the WNT4 promoter. Biochem Biophys Res Commun. 2006;339:1120-8 pubmed
    ..We further analyzed the WNT4 promoter, which was induced by p63 and p73 but not p53, in order to clarify the mechanism of differential target ..
  4. Philibert P, Biason Lauber A, Rouzier R, Pienkowski C, Paris F, Konrad D, et al. Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and müllerian duct abnormalities: a French collaborative study. J Clin Endocrinol Metab. 2008;93:895-900 pubmed publisher
    Müllerian duct development depends on gene and hormone interactions. Female Wnt4-knockout mice lack müllerian ducts and are virilized due to the inappropriate expression of the enzymes required for androgen production (normally ..
  5. Miyakoshi T, Takei M, Kajiya H, Egashira N, Takekoshi S, Teramoto A, et al. Expression of Wnt4 in human pituitary adenomas regulates activation of the beta-catenin-independent pathway. Endocr Pathol. 2008;19:261-73 pubmed publisher
    ..A member of the Wnt family of genes, Wnt4, has been known to regulate proliferation of anterior pituitary cell types in the mouse during embryonic ..
  6. Li Q, Kannan A, Das A, Demayo F, Hornsby P, Young S, et al. WNT4 acts downstream of BMP2 and functions via ?-catenin signaling pathway to regulate human endometrial stromal cell differentiation. Endocrinology. 2013;154:446-57 pubmed publisher
    ..Using gene expression profiling, we identified wingless-related murine mammary tumor virus integration site 4 (WNT4) as a target of BMP2 regulation during decidualization...
  7. Camden A, Szwarc M, Chadchan S, DeMayo F, O Malley B, Lydon J, et al. Growth regulation by estrogen in breast cancer 1 (GREB1) is a novel progesterone-responsive gene required for human endometrial stromal decidualization. Mol Hum Reprod. 2017;23:646-653 pubmed publisher
    ..05 and P < 0.01). Finally, GREB1 knock down signficantly reduced expression of the PR target genes WNT4 and FOXOA1 (P < 0.05 and P < 0.01, respectively). This study used the Nuclear Receptor Signaling Atlas...
  8. Ma Z, Lv X, Zhan L, Chen L, Zou Q, Xiang J, et al. Human urokinase-type plasminogen activator gene-modified bone marrow-derived mesenchymal stem cells attenuate liver fibrosis in rats by down-regulating the Wnt signaling pathway. World J Gastroenterol. 2016;22:2092-103 pubmed publisher
    ..31% ± 1.21%). Both protein and mRNA expression of β-catenin, Wnt4 and Wnt5a was down-regulated in liver tissues following uPA gene modified BMSCs treatment when compared with the ..
  9. Zhu X, Zhang Z, Han G, Han J, Qiu D. Overexpression of miR?214 promotes the progression of human osteosarcoma by regulating the Wnt/??catenin signaling pathway. Mol Med Rep. 2017;15:1884-1892 pubmed publisher
    ..Of note, infection with the miR?214 lentivirus did not affect the levels of Wnt1, Wnt2, Wnt4, Axin or glycogen synthase kinase ? in the U2OS cells, whereas the expression levels of ??catenin in the MG63 cells ..
  10. Alvarado D, Hawkins R, Bashiardes S, Veile R, Ku Y, Powder K, et al. An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear. J Neurosci. 2011;31:4535-43 pubmed publisher
    ..These pathways intersect on WNT4, which is also necessary for proliferation...
  11. Simitsidellis I, Gibson D, Cousins F, Esnal Zufiaurre A, Saunders P. A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus. Endocrinology. 2016;157:2116-28 pubmed publisher
    ..by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands...
  12. Serra A, Denzer F, Hiort O, Barth T, Henne Bruns D, Barbi G, et al. Uniparental Disomy in Somatic Mosaicism 45,X/46,XY/46,XX Associated with Ambiguous Genitalia. Sex Dev. 2015;9:136-43 pubmed publisher
    ..DNA sequencing revealed intact sequences in SOX9, WNT4, NR0B1, NR5A1, CYP21A2, SRY, AR, and DHH...
  13. Yu M, Liu W, Wang J, Qin J, Wang Y, Wang Y. Effects of tamoxifen on autosomal genes regulating ovary maintenance in adult mice. Environ Sci Pollut Res Int. 2015;22:20234-44 pubmed publisher
    ..Accordingly, expression of the ovary development marker, forkhead transcription factor (FOXL2), and WNT4/FST signaling, were depressed. The levels of protein expression changed consistently with the target genes...
  14. Boucsein A, Benzler J, Hempp C, Stöhr S, Helfer G, Tups A. Photoperiodic and Diurnal Regulation of WNT Signaling in the Arcuate Nucleus of the Female Djungarian Hamster, Phodopus sungorus. Endocrinology. 2016;157:799-809 pubmed publisher
    ..Furthermore, they suggest that this pathway plays a key role in the neuroendocrine regulation of body weight and integration of the leptin signal. ..
  15. Al Naib A, Tucker H, Xie G, Keisler D, Bartol F, Rhoads R, et al. Prepubertal tamoxifen treatment affects development of heifer reproductive tissues and related signaling pathways. J Dairy Sci. 2016;99:5780-5792 pubmed publisher
    ..receptor ? (ESR1) and ? (ESR2) mRNA, ESR1 protein, IGFI, progesterone receptor, total growth hormone receptor, WNT4, WNT5A, and WNT7A mRNA, in addition to mitogen-activated protein kinase (MAPK) and phosphorylated MAPK proteins ..
  16. Al Hendy A, Laknaur A, Diamond M, Ismail N, Boyer T, Halder S. Silencing Med12 Gene Reduces Proliferation of Human Leiomyoma Cells Mediated via Wnt/β-Catenin Signaling Pathway. Endocrinology. 2017;158:592-603 pubmed publisher
    ..Med12 knockdown cells showed significantly (P < 0.05) reduced levels of Wnt4 and β-catenin proteins as well as cell proliferation, as compared with scrambled control cells...
  17. Chang Y, Hsu S, Yang C, Sung P, Chen Y, Huang T, et al. Enhanced protection against renal ischemia-reperfusion injury with combined melatonin and exendin-4 in a rodent model. Exp Biol Med (Maywood). 2016;241:1588-602 pubmed publisher
    ..target of rapamycin) biomarkers, as well the podocyte dysfunction biomarkers (Wnt1/Wnt4/?-catenin) displayed a pattern identical to that of creatinine level among the five groups (all p?<?0.001)...
  18. Huang Y, Zhang S, Fang X, Qin L, Fan Y, Ding D, et al. Plasma miR-199a-5p is increased in neutrophilic phenotype asthma patients and negatively correlated with pulmonary function. PLoS ONE. 2018;13:e0193502 pubmed publisher
    ..In vitro experiment, miR-199a-5p mimics inhibited the protein expressions of WNT2 and WNT4, decreased the c-myc expression and dramatically increased the Sm-MHC expression in HASMCs...
  19. Prathibha Y, Senthilkumaran B. Involvement of pax2 in ovarian development and recrudescence of catfish: a role in steroidogenesis. J Endocrinol. 2016;231:181-195 pubmed
    ..reduced the expression of various transcripts related to ovarian development like signaling molecules such as wnt4 and wnt5, estrogen receptors, several steroidogenic enzymes and transcription factors...
  20. Hallman M, Haapalainen A, Huusko J, Karjalainen M, Zhang G, Muglia L, et al. Spontaneous premature birth as a target of genomic research. Pediatr Res. 2019;85:422-431 pubmed publisher
    ..For example, selenocysteine-specific elongation factor (EEFSEC) influences synthesis of selenoproteins. WNT4 regulates decidualization, while a heat-shock protein family A (HSP70) member 1 like, HSPAIL, influences expression ..
  21. Schlessinger D, Garcia Ortiz J, Forabosco A, Uda M, Crisponi L, Pelosi E. Determination and stability of gonadal sex. J Androl. 2010;31:16-25 pubmed publisher
    ..In the soma, ablation of Foxl2 or the independently expressed gene Wnt4 (likely downstream of Rspo1) can produce partial testis differentiation in XX mice, and the double knockout results ..
  22. Liu Z, Ren Y, Pangas S, Adams J, Zhou W, Castrillon D, et al. FOXO1/3 and PTEN Depletion in Granulosa Cells Promotes Ovarian Granulosa Cell Tumor Development. Mol Endocrinol. 2015;29:1006-24 pubmed publisher
    ..and quantitative PCR analyses of mouse GCTs further confirmed expression of specific genes (Foxl2, Gata4, and Wnt4) controlling granulosa cell fate specification and proliferation, whereas others (Emx2, Nr0b1, Rspo1, and Wt1) were ..
  23. Ren Y, Liu Z, Mullany L, Fan C, Richards J. Growth Arrest Specific-1 (GAS1) Is a C/EBP Target Gene That Functions in Ovulation and Corpus Luteum Formation in Mice. Biol Reprod. 2016;94:44 pubmed publisher
    ..Interestingly, levels of mRNA for a number of genes (Cyp11a1, Star, Wnt4, Prlr, Cd52, and Sema3a) associated with luteinization are decreased in corpora lutea of Gas1 mutant mice as ..
  24. Muter J, Brighton P, Lucas E, Lacey L, Shmygol A, Quenby S, et al. Progesterone-Dependent Induction of Phospholipase C-Related Catalytically Inactive Protein 1 (PRIP-1) in Decidualizing Human Endometrial Stromal Cells. Endocrinology. 2016;157:2883-93 pubmed publisher
    ..of HESCs to deciduogenic cues, although the overall expression of differentiation markers, such as PRL, IGFBP1, and WNT4, was blunted...
  25. Chen K, Chen C, Wallace C, Chen Y, Yang C, Sung P, et al. Combined therapy with melatonin and exendin-4 effectively attenuated the deterioration of renal function in rat cardiorenal syndrome. Am J Transl Res. 2017;9:214-229 pubmed
    ..CD14/CD68), DNA/kidney-damaged (γ-H2AX/KIM-1) and podocyte/renal tubule dysfunction signaling (β-catenin/Wnt1/Wnt4) biomarkers in kidney tissue exhibited an identical pattern of creatinine level (all P<0.0001)...
  26. Wilson K, Park J, Curry T, Mishra B, Gossen J, Taniuchi I, et al. Core Binding Factor-? Knockdown Alters Ovarian Gene Expression and Function in the Mouse. Mol Endocrinol. 2016;30:733-47 pubmed publisher
    ..the affected transcripts are known regulators of ovulation and luteinization including Sfrp4, Sgk1, Lhcgr, Prlr, Wnt4, and Edn2 as well as many genes not yet characterized in the ovary...
  27. Park J, Yi J, Park C, Lim Y, Lee K, Lee K, et al. Role of BRAF and RAS Mutations in Extrathyroidal Extension in Papillary Thyroid Cancer. Cancer Genomics Proteomics. 2016;13:171-81 pubmed
    ..Specifically, PAX8 and its downstream target WNT4 were differentially expressed according to mutation status in addition to ETE, indicating their critical roles in ..
  28. Monsivais D, Clementi C, Peng J, Fullerton P, Prunskaite Hyyryläinen R, Vainio S, et al. BMP7 Induces Uterine Receptivity and Blastocyst Attachment. Endocrinology. 2017;158:979-992 pubmed publisher
    ..defects also affected decidualization and resulted in decreased expression of decidual cell markers such as Wnt4, Cox2, Ereg, and Bmp2...
  29. Salamon S, Flisikowski K, Switonski M. Methylation Patterns of SOX3, SOX9, and WNT4 Genes in Gonads of Dogs with XX (SRY-Negative) Disorder of Sexual Development. Sex Dev. 2017;11:86-93 pubmed publisher
    ..was comparative methylation analysis of CpG islands in promoters of candidate genes for XX DSD: SOX9, SOX3, and WNT4. Methylation studies were performed on DNA extracted from formalin-fixed/paraffin-embedded or frozen gonads from 2 ..
  30. Parejo M, Wragg D, Henriques D, Vignal A, Neuditschko M. Genome-wide scans between two honeybee populations reveal putative signatures of human-mediated selection. Anim Genet. 2017;48:704-707 pubmed publisher
    ..Of particular interest is a selection signature on chromosome 1, which corresponds to the WNT4 gene, the family of which is conserved across the animal kingdom with a variety of functions...
  31. Zhou S, Eid K, Glowacki J. Cooperation between TGF-beta and Wnt pathways during chondrocyte and adipocyte differentiation of human marrow stromal cells. J Bone Miner Res. 2004;19:463-70 pubmed
    ..by macroarray, RT-PCR, and Western blot, TGF-beta activated genes in the TGF-beta/Smad pathway, upregulated Wnt2, Wnt4, Wnt5a, Wnt7a, Wnt10a, and Wnt co-receptor LRP5, and increased nuclear accumulation and stability of beta-catenin ..
  32. Liu R, Li N, Lin Y, Wang M, Peng Y, Lewi K, et al. Glucagon Like Peptide-1 Promotes Adipocyte Differentiation via the Wnt4 Mediated Sequestering of Beta-Catenin. PLoS ONE. 2016;11:e0160212 pubmed publisher
    ..The expression of Wnt4 was upregulated in the process of adipocyte differentiation, which was further enhanced by treatment with GLP-1...
  33. Jääskeläinen M, Prunskaite Hyyryläinen R, Naillat F, Parviainen H, Anttonen M, Heikinheimo M, et al. WNT4 is expressed in human fetal and adult ovaries and its signaling contributes to ovarian cell survival. Mol Cell Endocrinol. 2010;317:106-11 pubmed publisher
    b>WNT4 plays an important role in female sexual development and ovarian function. WNT4-deficiency leads disturbed development of the internal genitalia in mouse and human, and to a dramatic reduction of mouse oocytes...
  34. Chen Z, Zhu J, Fu Y, Richman A, Han Z. Wnt4 is required for ostia development in the Drosophila heart. Dev Biol. 2016;413:188-98 pubmed publisher
    ..We observed high levels of Wnt4 gene expression in Drosophila ostia progenitor cells, immediately prior to morphological differentiation of these ..
  35. Huang Z, Feng Y. Exosomes Derived From Hypoxic Colorectal Cancer Cells Promote Angiogenesis Through Wnt4-Induced ?-Catenin Signaling in Endothelial Cells. Oncol Res. 2017;25:651-661 pubmed publisher
    ..Furthermore, we discovered that these exosomes enriched with Wnt4 were dependent on HIF1?. Exosomal Wnt4 increased ?-catenin nuclear translocation in endothelial cells...
  36. Böhne A, Wilson C, Postlethwait J, Salzburger W. Variations on a theme: Genomics of sex determination in the cichlid fish Astatotilapia burtoni. BMC Genomics. 2016;17:883 pubmed
    ..LG5, the sex chromosome of the lab strain, is a fusion chromosome in A. burtoni. Wnt4 is located on this chromosome, representing the best candidate identified so far for the master sex-determining ..
  37. Zhang H, Yang Z, Duan C, Geng S, Wang K, Yu H, et al. WNT4 acts downstream of BMP2 to mediate the regulation of ATRA signaling on RUNX1 expression: Implications for terminal differentiation of antler chondrocytes. J Cell Physiol. 2018;233:1129-1145 pubmed publisher
    ..analysis evidenced that ATRA might induce chondrocyte terminal differentiation and modulate the expression of BMP2, WNT4, and RUNX1 through RAR?/RXR?...
  38. Canto P, Razo S, Söderlund D, Calzada León R, de la Luz Ruiz Reyes M, Ramon G, et al. Screening for mutations in the WNT-4 gene in patients with 46,XX true hermaphroditism. Mol Genet Metab. 2004;83:341-3 pubmed
    ..Direct sequencing of all five exons demonstrated no mutant alleles in any of the patients. The possibility of the existence of causative mutations in the untranslated regions of WNT-4, or within introns cannot be ruled out. ..
  39. Riordan N, George B, Chandler T, McKenna R. Case report of non-healing surgical wound treated with dehydrated human amniotic membrane. J Transl Med. 2015;13:242 pubmed publisher
    ..Amniotic AlphaPatches contain concentrated molecules of PGE2, WNT4, and GDF-11 which have angiogenic, trophic, and anti-inflammatory effects on tissues that may be useful in ..
  40. 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
    ..The Wnt family member Wnt4 has been shown to be required for the development of kidney, gonads, thymus, mammary and pituitary glands...
  41. Tanigawa S, Sharma N, Hall M, Nishinakamura R, Perantoni A. Preferential Propagation of Competent SIX2+ Nephronic Progenitors by LIF/ROCKi Treatment of the Metanephric Mesenchyme. Stem Cell Reports. 2015;5:435-47 pubmed publisher
    ..Passaged MM cells express the key stem cell regulators Six2 and Pax2 and remain competent to respond to WNT4 induction and form mature tubular epithelia and glomeruli...
  42. Liu M, Yang H. WNT4-like protein is a cortical granule component in mouse oocytes and functions in regulating preimplantation embryogenesis. Syst Biol Reprod Med. 2016;62:49-56 pubmed publisher
    ..In the present study, a 66 kDa wingless-type MMTV integration site family, member 4 (WNT4)-like protein, with mouse CG origin was identified...
  43. Haller M, Au J, O Neill M, Lamb D. 16p11.2 transcription factor MAZ is a dosage-sensitive regulator of genitourinary development. Proc Natl Acad Sci U S A. 2018;115:E1849-E1858 pubmed publisher
    ..in differential expression of several WNT morphogens required for normal GU development, including Wnt11 and Wnt4. MAZ knockdown also prevents efficient transition into S phase, affects transcription of cell-cycle ..
  44. Altchek A, Deligdisch L. The unappreciated Wnt-4 gene. J Pediatr Adolesc Gynecol. 2010;23:187-91 pubmed publisher
  45. Wang Y, Yang Q, Liu W, Yu M, Zhang Z, Cui X. DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice. Toxicol Appl Pharmacol. 2016;307:123-129 pubmed publisher
    ..2mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, ?-catenin and Fst...
  46. Torres R, Prior C, Garcia M, Puig J. A review of the implication of hypoxanthine excess in the physiopathology of Lesch-Nyhan disease. Nucleosides Nucleotides Nucleic Acids. 2016;35:507-516 pubmed
    ..Hypoxanthine deregulates early neuronal differentiation increasing WNT4 and EN1 gene expression.
  47. Salker M, Singh Y, Durairaj R, Yan J, Alauddin M, Zeng N, et al. LEFTY2 inhibits endometrial receptivity by downregulating Orai1 expression and store-operated Ca2+ entry. J Mol Med (Berl). 2018;96:173-182 pubmed publisher
    ..lumen in mice with recombinant LEFTY2 inhibits the expression of key receptivity genes, including Cox2, Bmp2, and Wnt4, and blocks embryo implantation...
  48. Drummond J, Reis F, Boson W, Silveira L, Bicalho M, De Marco L. Molecular analysis of the WNT4 gene in 6 patients with Mayer-Rokitansky-Küster-Hauser syndrome. Fertil Steril. 2008;90:857-9 pubmed
    Molecular analysis of the WNT4 gene in 6 patients with Mayer-Rokitansky-Küster-Hauser syndrome without androgen excess excluded this gene as a major cause of this syndrome, regardless of the subtype.
  49. Grinspon R, Rey R. Disorders of Sex Development with Testicular Differentiation in SRY-Negative 46,XX Individuals: Clinical and Genetic Aspects. Sex Dev. 2016;10:1-11 pubmed publisher
    ..g. SOX family genes, or failure of pro-ovarian/anti-testis genes, such as WNT4 and RSPO1, may underlie the development of testicular tissue...
  50. Williams L, Demir Eksi D, Shen Y, Lossie A, Chorich L, Sullivan M, et al. Genetic analysis of Mayer-Rokitansky-Kuster-Hauser syndrome in a large cohort of families. Fertil Steril. 2017;108:145-151.e2 pubmed publisher
    ..Some of the top candidate genes are WNT4, HNF1B, and LHX1...
  51. Sanchez L, Chaouiya C. Primary sex determination of placental mammals: a modelling study uncovers dynamical developmental constraints in the formation of Sertoli and granulosa cells. BMC Syst Biol. 2016;10:37 pubmed publisher
    ..and two further signals that define the transition from the initiation to the maintenance phases, by inhibiting the Wnt4 signalling pathway on the one hand, and by activating Foxl2 on the other hand...
  52. Wu X, Liang W, Guan H, Liu J, Liu L, Li H, et al. Exendin-4 promotes pancreatic ?-cell proliferation via inhibiting the expression of Wnt5a. Endocrine. 2017;55:398-409 pubmed publisher
    ..it was reported that exendin-4 promoted pancreatic ? cell proliferation by regulating the expression level of Wnt4. The present study was designed to investigate whether other Wnt isoforms take part in accommodation of ?-cell ..
  53. Brown B, Williams H, Bond A, Angelini G, Johnson J, George S. Carotid artery ligation induced intimal thickening and proliferation is unaffected by ageing. J Cell Commun Signal. 2018;12:529-537 pubmed publisher
    ..Our group previously demonstrated that in a murine model of vascular occlusion, Wnt4 protein expression and β-catenin signalling was upregulated which promoted vascular smooth muscle cell (VSMC) ..
  54. Jameson S, Lin Y, Capel B. Testis development requires the repression of Wnt4 by Fgf signaling. Dev Biol. 2012;370:24-32 pubmed publisher
    ..Adoption of the male testicular fate is associated with the repression of many female genes including Wnt4. However, the importance of repression of Wnt4 to the establishment of male development was not previously ..
  55. Dai J, Wang Z, Xu W, Zhang M, Zhu Z, Zhao X, et al. Paternal nicotine exposure defines different behavior in subsequent generation via hyper-methylation of mmu-miR-15b. Sci Rep. 2017;7:7286 pubmed publisher
    ..As the target gene of mmu-miR-15b, Wnt4 expression was elevated in the thalamus of F1 mice due to the inheritance of DNA methylation patterns from the ..
  56. Elizalde C, Campa V, Caro M, Schlangen K, Aransay A, Vivanco M, et al. Distinct roles for Wnt-4 and Wnt-11 during retinoic acid-induced neuronal differentiation. Stem Cells. 2011;29:141-53 pubmed publisher
    ..These observations highlight the distinct roles of two noncanonical Wnts during the early stages of retinoic acid-induced neuronal differentiation. ..
  57. Durham A, McLaren A, Hayes B, Caramori G, Clayton C, Barnes P, et al. Regulation of Wnt4 in chronic obstructive pulmonary disease. FASEB J. 2013;27:2367-81 pubmed publisher
    ..Using microarray analysis of bronchial biopsy samples from patients with COPD and controls, we identified Wnt4 as being up-regulated in COPD...
  58. Lee C, Buttitta L, May N, Kispert A, Fan C. SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. Development. 2000;127:109-18 pubmed
    ..We further show that SFRP2-expressing cells can reduce the dermomyotome-inducing activity of WNT1 and WNT4, but not that of WNT3a...
  59. Hessinger C, Technau G, Rogulja Ortmann A. The Drosophila Hox gene Ultrabithorax acts in both muscles and motoneurons to orchestrate formation of specific neuromuscular connections. Development. 2017;144:139-150 pubmed publisher
    ..segments A2 to A7, RP motoneurons innervate the ventrolateral muscles VL1-4, with VL1 and VL2 being innervated in a Wnt4-dependent manner...
  60. Saulnier D, Ghanbari H, Brändli A. Essential function of Wnt-4 for tubulogenesis in the Xenopus pronephric kidney. Dev Biol. 2002;248:13-28 pubmed
    ..We therefore investigated the expression of Wnt genes during the pronephric kidney development in Xenopus. Wnt4 was found to be associated with developing pronephric tubules, but was absent from the pronephric duct...
  61. Christopoulos P, Gazouli M, Fotopoulou G, Creatsas G. The role of genes in the development of Mullerian anomalies: where are we today?. Obstet Gynecol Surv. 2009;64:760-8 pubmed publisher
  62. Filippone M, Di Palma T, Lucci V, Zannini M. Pax8 modulates the expression of Wnt4 that is necessary for the maintenance of the epithelial phenotype of thyroid cells. BMC Mol Biol. 2014;15:21 pubmed publisher
    ..of the gene expression profile of FRTL-5 differentiated thyroid cells after the silencing of Pax8 identified Wnt4 as a novel target...
  63. Fontana L, Gentilin B, Fedele L, Gervasini C, Miozzo M. Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Clin Genet. 2017;91:233-246 pubmed publisher
    ..Several candidate causative genes have been investigated, but to date only WNT4 has been associated with MRKH with hyperandrogenism...
  64. Li Y, Wang M, Huang B, Ping Y, You J, Gao J. Transcriptome-wide elucidation of liposomal formulations for anticancer drug delivery. Int J Nanomedicine. 2017;12:8557-8572 pubmed publisher
    ..equivalent dosage of Dox, free Dox substantially changed the expression of ANK1, ACTA2, GPR87, GDF15, FZD6, and WNT4 in MCF-7 cells...
  65. Surendran K, Simon T, Liapis H, McGuire J. Matrilysin (MMP-7) expression in renal tubular damage: association with Wnt4. Kidney Int. 2004;65:2212-22 pubmed
    ..A relationship to Wnt4, which is also induced in renal injury, was determined by RPA and in situ hybridization...
  66. Peltoketo H, Allinen M, Vuosku J, Kujala S, Lundan T, Salminen A, et al. Characterization and expression of the human WNT4; lack of associated germline mutations in high--to moderate--risk breast and ovarian cancer. Cancer Lett. 2004;213:83-90 pubmed
    b>Wnt4 is needed for correct development of several tissues in the mouse, and WNT4 is found here to be expressed in a temporal manner in human embryonic tissues. In addition, WNT4 mRNA is seen in several adult tissues. The 1...
  67. Shoar Z, Ganguly T, Anderson C, De Luca F, Suarez E. Absence of WNT4 gene mutation in a patient with MURCS association. J Pediatr Endocrinol Metab. 2014;27:555-9 pubmed publisher
    ..MURCS association, obesity, and clinical findings of hyperandrogenism who did not show any exonic mutation of the WNT4 gene...
  68. Weber Hall S, Phippard D, Niemeyer C, Dale T. Developmental and hormonal regulation of Wnt gene expression in the mouse mammary gland. Differentiation. 1994;57:205-14 pubmed
    ..Finally, Wnt-2, Wnt-4 and Wnt-5b were shown to be regulated by ovarian hormones. These results suggest that Wnt genes have non-redundant roles in breast development and may be involved in the hormonal regulation of mammary growth...
  69. Lescher B, Haenig B, Kispert A. sFRP-2 is a target of the Wnt-4 signaling pathway in the developing metanephric kidney. Dev Dyn. 1998;213:440-51 pubmed
  70. Philibert P, Biason Lauber A, Gueorguieva I, Stuckens C, Pienkowski C, Lebon Labich B, et al. Molecular analysis of WNT4 gene in four adolescent girls with mullerian duct abnormality and hyperandrogenism (atypical Mayer-Rokitansky-Küster-Hauser syndrome). Fertil Steril. 2011;95:2683-6 pubmed publisher
    ..Molecular analysis of the WNT4 gene permitted us to identify a new mutation (p.A233T)...
  71. Chang X, Qin Y, Xu C, Li G, Zhao X, Chen Z. Mutations in WNT4 are not responsible for Müllerian duct abnormalities in Chinese women. Reprod Biomed Online. 2012;24:630-3 pubmed publisher
    The WNT4 gene plays a crucial role in sexual differentiation and female genital tract development...
  72. Ravel C, Lorenço D, Dessolle L, Mandelbaum J, McElreavey K, Darai E, et al. Mutational analysis of the WNT gene family in women with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril. 2009;91:1604-7 pubmed publisher
    ..This supports the hypothesis that mutations in the coding sequence of WNT4, WNT5A, WNT7A, and WNT9B are not responsible for the Mayer-Rokitansky-Kuster-Hauser syndrome.
  73. Albertsen H, Chettier R, Farrington P, Ward K. Genome-wide association study link novel loci to endometriosis. PLoS ONE. 2013;8:e58257 pubmed publisher
    ..Three of the SNPs we identify associated at P<5×10(-8) in our combined analysis belong to two loci: LINC00339-WNT4 on 1p36.12 (rs2235529; P?=?8.65×10(-9), OR?=?1.29, CI?=?1.18-1.40) and RND3-RBM43 on 2q23.3 (rs1519761; P?=?4...
  74. Hendrickx G, Boudin E, Steenackers E, Nielsen T, Andersen M, Brixen K, et al. Genetic Screening of WNT4 and WNT5B in Two Populations with Deviating Bone Mineral Densities. Calcif Tissue Int. 2017;100:244-249 pubmed publisher
    A role for WNT4 and WNT5B in bone metabolism was indicated by genome-wide association studies (GWAS) and a Wnt4 knockout mouse model...
  75. Tayyeb A, Shahzad N, Ali G. Differentiation of Mesenchymal Stem Cells Towards Nephrogenic Lineage and Their Enhanced Resistance to Oxygen Peroxide-induced Oxidative Stress. Iran J Kidney Dis. 2017;11:271-279 pubmed
    ..Both types of differentiated cells showed significant expression of pronephrogenic markers (Wnt4, Wt1, and Pax2) and renal epithelial markers (Ecad and ZO1)...
  76. Biason Lauber A, Konrad D, Navratil F, Schoenle E. A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman. N Engl J Med. 2004;351:792-8 pubmed
    b>WNT4, a secreted protein that suppresses male sexual differentiation, is thought to repress the biosynthesis of gonadal androgen in female mammals...
  77. Lakhal B, Ben Hadj Khalifa S, Bouali N, Braham R, Hatem E, Saad A. Mutational screening of SF1 and WNT4 in Tunisian women with premature ovarian failure. Gene. 2012;509:298-301 pubmed publisher
    b>WNT4 and SF1 genes play an important role in ovarian development. They constitute coherent candidate genes associated with premature ovarian failure (POF) pathogenesis...
  78. Chang J, Sonoyama W, Wang Z, Jin Q, Zhang C, Krebsbach P, et al. Noncanonical Wnt-4 signaling enhances bone regeneration of mesenchymal stem cells in craniofacial defects through activation of p38 MAPK. J Biol Chem. 2007;282:30938-48 pubmed
    ..Taken together, our results reveal that noncanonical Wnt signaling could also play a role in osteogenic differentiation. Wnt-4 may have a potential use in improving bone regeneration and repair of craniofacial defects. ..
  79. Hamilton P, Sun Y, Henry J. Lens regeneration from the cornea requires suppression of Wnt/β-catenin signaling. Exp Eye Res. 2016;145:206-215 pubmed publisher
    ..Numerous frizzled receptors (fzd1, fzd2, fzd3, fzd4, fzd6, fzd7, fzd8, and fzd10) and wnt ligands (wnt2b.a, wnt3a, wnt4, wnt5a, wnt5b, wnt6, wnt7b, wnt10a, wnt11, and wnt11b) are expressed in the cornea epithelium, demonstrating that ..
  80. Yang X, Ikhwanuddin M, Li X, Lin F, Wu Q, Zhang Y, et al. Comparative Transcriptome Analysis Provides Insights into Differentially Expressed Genes and Long Non-Coding RNAs between Ovary and Testis of the Mud Crab (Scylla paramamosain). Mar Biotechnol (NY). 2018;20:20-34 pubmed publisher
    ..Homologous genes involved in sex determination and gonadal development pathways (Sxl-Tra/Tra-2-Dsx/Fru, Wnt4, thyroid hormone synthesis pathway, etc.) were identified...
  81. Vainio S. Nephrogenesis regulated by Wnt signaling. J Nephrol. 2003;16:279-85 pubmed
    ..The varied role of Wnt signaling in the developing kidney is discussed. ..
  82. Pikkarainen T, Nurmi T, Sasaki T, Bergmann U, Vainio S. Role of the extracellular matrix-located Mac-2 binding protein as an interactor of the Wnt proteins. Biochem Biophys Res Commun. 2017;491:953-957 pubmed publisher
    ..Here, we expressed epitope-tagged Wnt4 in HEK293 cells, and identified Mac-2 binding protein (Mac-2BP) as its binding partner in the serum-free ..
  83. Zhang G, Feenstra B, Bacelis J, Liu X, Muglia L, Juodakis J, et al. Genetic Associations with Gestational Duration and Spontaneous Preterm Birth. N Engl J Med. 2017;377:1156-1167 pubmed publisher
    ..In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration...
  84. Farah O, Biechele S, Rossant J, Dufort D. Porcupine-dependent Wnt activity within the uterine epithelium is essential for fertility. Biol Reprod. 2017;97:688-697 pubmed publisher
    ..of Porcupine in the epithelium resulted in the stromal dysregulation of members of the Wnt signaling pathway (Lef1, Wnt4, and Wnt16), dysregulation of receptors and ligands in the Notch signaling pathway (Notch1, Notch4, and Dll4) as ..
  85. Nyholt D, Low S, Anderson C, Painter J, Uno S, Morris A, et al. Genome-wide association meta-analysis identifies new endometriosis risk loci. Nat Genet. 2012;44:1355-9 pubmed publisher
    ..6 × 10(-3)), and we confirm association of rs7521902 at 1p36.12 near WNT4. In addition, we establish an association of rs13394619 in GREB1 at 2p25...
  86. Liang Y, Li Y, Liu K, Chen P, Wang D. Expression and Significance of WNT4 in Ectopic and Eutopic Endometrium of Human Endometriosis. Reprod Sci. 2016;23:379-85 pubmed publisher
    The objective was to investigate the expression of the WNT4 gene in ectopic endometrium and eutopic endometrium (EU) during endometriosis and the relationship of WNT4 expression with the menstrual cycle...
  87. Nielson C, Liu C, Smith A, Ackert Bicknell C, Reppe S, Jakobsdottir J, et al. Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2. J Bone Miner Res. 2016;31:2085-2097 pubmed publisher
    ..We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36...
  88. Suwa T, Chen M, Hawks C, Hornsby P. Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex. J Endocrinol. 2003;178:149-58 pubmed
    ..Consistent with previously published data on the effects of Wnt4 gene disruption in the mouse, we found only WNT4 expression within the WNT family in both human and mouse RNA...
  89. Wang G, Zhang Z, Chen C, Zhang Y, Zhang C. Dysfunction of WNT4/WNT5A in deciduas: possible relevance to the pathogenesis of preeclampsia. J Hypertens. 2016;34:719-27 pubmed publisher
    ..b>WNT4 and WNT5A are highly expressed in the deciduas of mice and human beings; their deficiency causes the abnormality of ..
  90. Bagheri Fam S, Bird A, Zhao L, Ryan J, Yong M, Wilhelm D, et al. Testis Determination Requires a Specific FGFR2 Isoform to Repress FOXL2. Endocrinology. 2017;158:3832-3843 pubmed publisher
    ..Together with previous findings, our data suggest that testis determination involves FGFR2c-mediated repression of both the WNT4- and FOXL2-driven ovarian-determining pathways.
  91. Vivante A, Mark Danieli M, Davidovits M, Harari Steinberg O, Omer D, Gnatek Y, et al. Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling. J Am Soc Nephrol. 2013;24:550-8 pubmed publisher
    ..mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1...
  92. Bashamboo A, Donohoue P, Vilain E, Rojo S, Calvel P, Seneviratne S, et al. A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development. Hum Mol Genet. 2016;25:3446-3453 pubmed publisher
    ..g. WNT4); however, the genetic cause of the more common non-syndromic forms is unknown...