Gene Symbol: Wt1
Description: Wilms tumor 1 homolog
Alias: D630046I19Rik, Wt-1, Wilms tumor protein homolog
Species: mouse
Products:     Wt1

Top Publications

  1. Cacalano G, Farinas I, Wang L, Hagler K, Forgie A, Moore M, et al. GFRalpha1 is an essential receptor component for GDNF in the developing nervous system and kidney. Neuron. 1998;21:53-62 pubmed
  2. Discenza M, Pelletier J. Insights into the physiological role of WT1 from studies of genetically modified mice. Physiol Genomics. 2004;16:287-300 pubmed
    The identification of WT1 gene mutations in children with WAGR and Denys-Drash syndromes pointed toward a role for WT1 in genitourinary system development...
  3. Patterson L, Pembaur M, Potter S. Hoxa11 and Hoxd11 regulate branching morphogenesis of the ureteric bud in the developing kidney. Development. 2001;128:2153-61 pubmed
  4. Poladia D, Kish K, Kutay B, Hains D, Kegg H, Zhao H, et al. Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. Dev Biol. 2006;291:325-39 pubmed
    ..In metanephric mesenchymal rudiments, fgfr1 and fgfr2 appear to function downstream of Eya1 and Six1, but upstream of Six2, Sall1, and Pax2. Finally, this is the first example of renal aplasia in a conditional knockout model. ..
  5. Patek C, Fleming S, Miles C, Bellamy C, Ladomery M, Spraggon L, et al. Murine Denys-Drash syndrome: evidence of podocyte de-differentiation and systemic mediation of glomerulosclerosis. Hum Mol Genet. 2003;12:2379-94 pubmed
    Denys-Drash syndrome (DDS) is caused by dominant mutations of the Wilms' tumour suppressor gene, WT1, and characterized by a nephropathy involving diffuse mesangial sclerosis, male pseudohermaphroditism and/or Wilms' tumourigenesis...
  6. Rumballe B, Georgas K, Combes A, Ju A, Gilbert T, Little M. Nephron formation adopts a novel spatial topology at cessation of nephrogenesis. Dev Biol. 2011;360:110-22 pubmed publisher
    ..We propose that this phase of nephron formation represents an acceleration of differentiation within the cap mesenchyme due to a displacement of signals within the nephrogenic niche. ..
  7. Chau Y, BROWNSTEIN D, Mjoseng H, Lee W, Buza Vidas N, Nerlov C, et al. Acute multiple organ failure in adult mice deleted for the developmental regulator Wt1. PLoS Genet. 2011;7:e1002404 pubmed publisher
    ..Mice deleted for the Wilms' tumour gene, Wt1, lack kidneys, gonads, and spleen and die at mid-gestation due to defective coronary vasculature...
  8. Armstrong J, Pritchard Jones K, Bickmore W, Hastie N, Bard J. The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo. Mech Dev. 1993;40:85-97 pubmed
    In the developing mouse, the Wilms' tumour gene, WT1, is first expressed in the intermediate mesenchyme lateral to the coelomic cavity (13 somite, early 9 dpc embryo)...
  9. Rackley R, Flenniken A, Kuriyan N, Kessler P, Stoler M, Williams B. Expression of the Wilms' tumor suppressor gene WT1 during mouse embryogenesis. Cell Growth Differ. 1993;4:1023-31 pubmed
    b>WT1 is a Wilms' tumor suppressor gene that maps to human chromosome 11p13 and encodes a putative transcription factor implicated in controlling normal urogenital development...

More Information


  1. Georgas K, Rumballe B, Wilkinson L, Chiu H, Lesieur E, Gilbert T, et al. Use of dual section mRNA in situ hybridisation/immunohistochemistry to clarify gene expression patterns during the early stages of nephron development in the embryo and in the mature nephron of the adult mouse kidney. Histochem Cell Biol. 2008;130:927-42 pubmed publisher
    ..We have analysed in detail the protein expression of Wt1, Calb1 Aqp1, Aqp2 and Umod using these antibodies...
  2. Dallosso A, Hancock A, Malik S, Salpekar A, King Underwood L, Pritchard Jones K, et al. Alternately spliced WT1 antisense transcripts interact with WT1 sense RNA and show epigenetic and splicing defects in cancer. RNA. 2007;13:2287-99 pubmed
    ..b>WT1 is a well-characterized developmental gene that is mutated in Wilms' tumor (WT) and acute myeloid leukaemia (AML) ..
  3. Rudat C, Kispert A. Wt1 and epicardial fate mapping. Circ Res. 2012;111:165-9 pubmed publisher
    ..Genetic lineage tracing systems based on Wt1 regulatory sequences provided evidence that epicardium-derived cells also adopt a myocardial fate in the mouse...
  4. Red Horse K, Ueno H, Weissman I, Krasnow M. Coronary arteries form by developmental reprogramming of venous cells. Nature. 2010;464:549-53 pubmed publisher
    ..Understanding this new reprogramming process and identifying the endogenous signals should suggest more natural ways of engineering coronary bypass grafts and revascularizing the heart. ..
  5. Self M, Lagutin O, Bowling B, Hendrix J, Cai Y, Dressler G, et al. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J. 2006;25:5214-28 pubmed
    ..We propose that in the developing kidney, Six2 activity is required for maintaining the mesenchymal progenitor population in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud...
  6. Tevosian S, Albrecht K, Crispino J, Fujiwara Y, Eicher E, Orkin S. Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2. Development. 2002;129:4627-34 pubmed
    ..By contrast, Wt1 and Sf1, which are expressed prior to Sry and necessary for gonad development in both sexes, were expressed ..
  7. Schnabel C, Godin R, Cleary M. Pbx1 regulates nephrogenesis and ureteric branching in the developing kidney. Dev Biol. 2003;254:262-76 pubmed
    ..Taken together, these data establish a role for Pbx1 in mesenchymal-epithelial signaling and demonstrate that Pbx1 is an essential regulator of mesenchymal function during renal morphogenesis. ..
  8. Gao F, Maiti S, Alam N, Zhang Z, Deng J, Behringer R, et al. The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis. Proc Natl Acad Sci U S A. 2006;103:11987-92 pubmed
    Mutation of the transcription factor and tumor suppressor gene WT1 results in a range of genitourinary anomalies in humans, including 46,XY gonadal dysgenesis, indicating that WT1 plays a critical role in sex determination...
  9. Greulich F, Farin H, Schuster Gossler K, Kispert A. Tbx18 function in epicardial development. Cardiovasc Res. 2012;96:476-83 pubmed publisher
  10. Burn S, Webb A, Berry R, Davies J, Ferrer Vaquer A, Hadjantonakis A, et al. Calcium/NFAT signalling promotes early nephrogenesis. Dev Biol. 2011;352:288-98 pubmed publisher
    ..We propose that the non-canonical Calcium/NFAT Wnt signalling pathway plays an important role in early mammalian renal development and is required for complete MET during nephrogenesis, potentially acting downstream of Wnt4. ..
  11. Cain J, Islam E, Haxho F, Chen L, Bridgewater D, Nieuwenhuis E, et al. GLI3 repressor controls nephron number via regulation of Wnt11 and Ret in ureteric tip cells. PLoS ONE. 2009;4:e7313 pubmed publisher
    ..Thus, GLI3 repressor controls nephron number by regulating ureteric tip cell expression of Wnt11 and Ret. ..
  12. Hu Y, Okumura L, Page D. Gata4 is required for formation of the genital ridge in mice. PLoS Genet. 2013;9:e1003629 pubmed publisher
    ..At least four genes (Lhx9, Sf1, Wt1, and Emx2) have been demonstrated to be required for subsequent growth and maintenance of the genital ridge...
  13. Christoffels V, Grieskamp T, Norden J, Mommersteeg M, Rudat C, Kispert A. Tbx18 and the fate of epicardial progenitors. Nature. 2009;458:E8-9; discussion E9-10 pubmed publisher
  14. Zhou B, von Gise A, Ma Q, RIVERA FELICIANO J, Pu W. Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium. Biochem Biophys Res Commun. 2008;375:450-3 pubmed publisher
    ..Both Nkx2-5- and Isl1-expressing progenitors contributed to the proepicardium and expressed Wt1 and Tbx18, markers of proepicardial progenitor cells...
  15. Gross I, Morrison D, Hyink D, Georgas K, English M, Mericskay M, et al. The receptor tyrosine kinase regulator Sprouty1 is a target of the tumor suppressor WT1 and important for kidney development. J Biol Chem. 2003;278:41420-30 pubmed
    b>WT1 encodes a transcription factor involved in kidney development and tumorigenesis...
  16. Hammes A, Guo J, Lutsch G, Leheste J, Landrock D, Ziegler U, et al. Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation. Cell. 2001;106:319-29 pubmed
    Alternative splicing of Wt1 results in the insertion or omission of the three amino acids KTS between zinc fingers 3 and 4. In vitro experiments suggest distinct molecular functions for + and -KTS isoforms...
  17. Birk O, Casiano D, Wassif C, Cogliati T, Zhao L, Zhao Y, et al. The LIM homeobox gene Lhx9 is essential for mouse gonad formation. Nature. 2000;403:909-13 pubmed
    ..Unlike mice lacking other genes that mediate early stages of gonadogenesis, Lhx9 mutants do not exhibit additional major developmental defects. Thus, LHX9 mutations may underlie certain forms of isolated gonadal agenesis in humans. ..
  18. Miyamoto N, Yoshida M, Kuratani S, Matsuo I, Aizawa S. Defects of urogenital development in mice lacking Emx2. Development. 1997;124:1653-64 pubmed
    ..Degeneration of the Wolffian duct and mesonephric tubules was also abnormally accelerated without the formation of the Mullerian duct. ..
  19. Niksic M, Slight J, Sanford J, Caceres J, Hastie N. The Wilms' tumour protein (WT1) shuttles between nucleus and cytoplasm and is present in functional polysomes. Hum Mol Genet. 2004;13:463-71 pubmed
    Mutations of the Wilms' tumour-1 (WT1) gene in humans can lead to childhood kidney cancer, life-threatening glomerular nephropathy and gonadal dysgenesis...
  20. Veith A, Klattig J, Dettai A, Schmidt C, Englert C, Volff J. Male-biased expression of X-chromosomal DM domain-less Dmrt8 genes in the mouse. Genomics. 2006;88:185-95 pubmed
    ..Dmrt8.1 mRNA was detected in Sertoli cells by in situ hybridization. In embryos, Dmrt8.2 shows a dynamic expression restricted to male and female gonads and might therefore be involved in sexual development in the mouse. ..
  21. Katoh Fukui Y, Miyabayashi K, Komatsu T, Owaki A, Baba T, Shima Y, et al. Cbx2, a polycomb group gene, is required for Sry gene expression in mice. Endocrinology. 2012;153:913-24 pubmed publisher
    ..However, testes remained hypoplastic in these mice, indicating that the size and the sex of the gonad are determined by different sets of genes. Our study implicates Cbx2 in testis differentiation through regulating Sry gene expression. ..
  22. Zhou B, Ma Q, Rajagopal S, Wu S, Domian I, RIVERA FELICIANO J, et al. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature. 2008;454:109-13 pubmed publisher
    ..Here we identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium-an epithelial sheet overlying the heart...
  23. Rao M, Pham J, Imam J, Maclean J, Murali D, Furuta Y, et al. Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis. Genes Dev. 2006;20:147-52 pubmed
    ..the principle by which naturally occurring microRNAs (miRNA) are made, we demonstrate that the Wilms' tumor 1 (WT1) transcription factor has an essential role in spermatogenesis...
  24. Carroll T, Park J, Hayashi S, Majumdar A, McMahon A. 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 pubmed
    ..Together these findings suggest that Wnt9b is a common organizing signal regulating diverse components of the mammalian urogenital system...
  25. Manuylov N, Zhou B, Ma Q, Fox S, Pu W, Tevosian S. Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation. Dev Biol. 2011;353:229-41 pubmed publisher
    ..Our results now demonstrate that these two genes also have non-overlapping essential functions in testis development. ..
  26. Cai C, Martin J, Sun Y, Cui L, Wang L, Ouyang K, et al. A myocardial lineage derives from Tbx18 epicardial cells. Nature. 2008;454:104-8 pubmed publisher
    ..The pluripotency of Tbx18 proepicardial cells provides a theoretical framework for applying these progenitors to effect cardiac repair and regeneration. ..
  27. Ratelade J, Arrondel C, Hamard G, Garbay S, Harvey S, Biebuyck N, et al. A murine model of Denys-Drash syndrome reveals novel transcriptional targets of WT1 in podocytes. Hum Mol Genet. 2010;19:1-15 pubmed publisher
    The Wilms tumor-suppressor gene WT1, a key player in renal development, also has a crucial role in maintenance of the glomerulus in the mature kidney...
  28. Nishinakamura R, Matsumoto Y, Nakao K, Nakamura K, Sato A, Copeland N, et al. Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development. 2001;128:3105-15 pubmed
    ..Sall1 is therefore essential for ureteric bud invasion, the initial key step for metanephros development. ..
  29. Guadix J, Ruiz Villalba A, Lettice L, Velecela V, Muñoz Chápuli R, Hastie N, et al. Wt1 controls retinoic acid signalling in embryonic epicardium through transcriptional activation of Raldh2. Development. 2011;138:1093-7 pubmed publisher
    ..In the current study, we show that Wt1-null epicardial cells display decreased expression of Raldh2 both in vivo and in vitro...
  30. Wu M, Smith C, Hall J, Lee I, Luby Phelps K, Tallquist M. Epicardial spindle orientation controls cell entry into the myocardium. Dev Cell. 2010;19:114-25 pubmed publisher
    ..Taken together, these data suggest that directed mitotic spindle orientation contributes to epicardial EMT and implicate a junctional complex of beta-catenin and Numb in the regulation of spindle orientation. ..
  31. Ji S, Hao J, Li L, Zhang J, Zheng Q, Li X, et al. Expression of inhibin-alpha is regulated synergistically by Wilms' tumor gene 1 (Wt1) and steroidogenic factor-1 (Sf1) in sertoli cells. PLoS ONE. 2013;8:e53140 pubmed publisher
    b>Wt1 encodes a zinc finger nuclear transcriptional factor, which is specifically expressed in testicular Sertoli cells and knockdown of Wt1 in Sertoli cells causes male mice subfertility. However, the underlying mechanism is still unclear...
  32. Xu P, Adams J, Peters H, Brown M, Heaney S, Maas R. Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet. 1999;23:113-7 pubmed
    ..In addition, our results suggest that an evolutionarily conserved Pax-Eya-Six regulatory hierarchy is used in mammalian ear and kidney development. ..
  33. Mendelsohn C, Batourina E, Fung S, Gilbert T, Dodd J. Stromal cells mediate retinoid-dependent functions essential for renal development. Development. 1999;126:1139-48 pubmed
    ..Since c-ret signaling is required for ureteric bud morphogenesis, loss of c-ret expression is a likely cause of impaired ureteric bud branching in RARalpha beta2(-) mutants. ..
  34. Xu P, Zheng W, Huang L, Maire P, Laclef C, Silvius D. Six1 is required for the early organogenesis of mammalian kidney. Development. 2003;130:3085-94 pubmed
    ..These analyses establish a role for Six1 in the initial inductive step for metanephric development. ..
  35. Grieshammer U, Cebrian C, Ilagan R, Meyers E, Herzlinger D, Martin G. FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. Development. 2005;132:3847-57 pubmed
    ..Thus, unlike other FGF family members, which regulate growth and branching morphogenesis of the collecting duct system, Fgf8 encodes a factor essential for gene regulation and cell survival at distinct steps in nephrogenesis. ..
  36. Ryan G, Steele Perkins V, Morris J, Rauscher F, Dressler G. Repression of Pax-2 by WT1 during normal kidney development. Development. 1995;121:867-75 pubmed
    ..We have examined the spatial and temporal expression patterns of Pax-2 and the Wilm's tumor suppresser protein WT1 with specific antibodies in developing mouse kidneys...
  37. von Gise A, Zhou B, Honor L, Ma Q, Petryk A, Pu W. WT1 regulates epicardial epithelial to mesenchymal transition through ?-catenin and retinoic acid signaling pathways. Dev Biol. 2011;356:421-31 pubmed publisher
    ..In the developing embryo, the epicardium expresses the transcriptional regulator Wilm's Tumor Gene 1 (Wt1). Through incompletely understood mechanisms, Wt1 inactivation derails normal heart development...
  38. Airik R, Bussen M, Singh M, Petry M, Kispert A. Tbx18 regulates the development of the ureteral mesenchyme. J Clin Invest. 2006;116:663-74 pubmed
    ..Our analysis also showed that the ureteral mesenchyme derives from a distinct cell population that is separated early in kidney development from that of other mesenchymal cells of the renal system. ..
  39. Zeng B, Ren X, Cao F, Zhou X, Zhang J. Developmental patterns and characteristics of epicardial cell markers Tbx18 and Wt1 in murine embryonic heart. J Biomed Sci. 2011;18:67 pubmed publisher
    ..The present study therefore aimed to examine the the expression of Tbx18 and Wt1 in embryonic heart and to identify whether Tbx18 and Wt1 themselves expressed in the cardiomyocyte...
  40. Hilliard S, Aboudehen K, Yao X, El Dahr S. Tight regulation of p53 activity by Mdm2 is required for ureteric bud growth and branching. Dev Biol. 2011;353:354-66 pubmed publisher
    ..These results demonstrate a critical and cell autonomous role for Mdm2 in the UB lineage. Mdm2-mediated inhibition of p53 activity is a prerequisite for renal organogenesis. ..
  41. Kusaka M, Katoh Fukui Y, Ogawa H, Miyabayashi K, Baba T, Shima Y, et al. Abnormal epithelial cell polarity and ectopic epidermal growth factor receptor (EGFR) expression induced in Emx2 KO embryonic gonads. Endocrinology. 2010;151:5893-904 pubmed publisher
    ..Our results strongly suggest that Emx2 is required for regulation of tight junction assembly and allowing migration of the gonadal epithelia to the mesenchyme, which are possibly mediated by suppression of Egfr expression...
  42. Luo G, Hofmann C, Bronckers A, Sohocki M, Bradley A, Karsenty G. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev. 1995;9:2808-20 pubmed
    ..In addition, BMP-7-deficient mice have eye defects that appear to originate during lens induction. Finally, BMP-7-deficient mice also have skeletal patterning defects restricted to the rib cage, the skull, and the hindlimbs. ..
  43. Miyamoto Y, Taniguchi H, Hamel F, Silversides D, Viger R. A GATA4/WT1 cooperation regulates transcription of genes required for mammalian sex determination and differentiation. BMC Mol Biol. 2008;9:44 pubmed publisher
  44. Hosen N, Shirakata T, Nishida S, Yanagihara M, Tsuboi A, Kawakami M, et al. The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis. Leukemia. 2007;21:1783-91 pubmed
    The Wilms' tumor gene WT1 is overexpressed in most of human leukemias regardless of disease subtypes...
  45. Zhou B, von Gise A, Ma Q, Hu Y, Pu W. Genetic fate mapping demonstrates contribution of epicardium-derived cells to the annulus fibrosis of the mammalian heart. Dev Biol. 2010;338:251-61 pubmed publisher
    ..Abnormalities of this differentiation process may underlie development of some forms of re-entrant atrioventricular tachycardia. ..
  46. Esquela A, Lee S. Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol. 2003;257:356-70 pubmed
    ..Our studies suggest that Gdf11 may be important in directing the initial outgrowth of the ureteric bud from the Wolffian duct by controlling the expression of Gdnf in the metanephric mesenchyme. ..
  47. Hartwig S, Bridgewater D, Di Giovanni V, Cain J, Mishina Y, Rosenblum N. BMP receptor ALK3 controls collecting system development. J Am Soc Nephrol. 2008;19:117-24 pubmed publisher
    ..In summary, normal kidney development requires ALK3-dependent BMP signaling, which controls ureteric bud branching. ..
  48. Schnabel C, Selleri L, Cleary M. Pbx1 is essential for adrenal development and urogenital differentiation. Genesis. 2003;37:123-30 pubmed
    ..These findings establish a Pbx1-dependent pathway that regulates the expansion of SF-1 positive cells essential for adrenal formation and gonadal differentiation and demonstrate an early requirement for Pbx1 in urogenital development. ..
  49. Stark K, Vainio S, Vassileva G, McMahon A. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature. 1994;372:679-83 pubmed
    ..Thus, Wnt-4 appears to act as an autoinducer of the mesenchyme to epithelial transition that underlies nephron development. ..
  50. Gao F, Maiti S, Sun G, Ordonez N, Udtha M, Deng J, et al. The Wt1+/R394W mouse displays glomerulosclerosis and early-onset renal failure characteristic of human Denys-Drash syndrome. Mol Cell Biol. 2004;24:9899-910 pubmed
    ..To help elucidate this, we generated a mouse strain carrying the missense mutation Wt1 R394W, which predisposes humans to glomerulosclerosis and early-onset renal failure (Denys-Drash syndrome [DDS])...
  51. Carpenter B, Hill K, Charalambous M, Wagner K, Lahiri D, James D, et al. BASP1 is a transcriptional cosuppressor for the Wilms' tumor suppressor protein WT1. Mol Cell Biol. 2004;24:537-49 pubmed
    The Wilms' tumor suppressor protein WT1 is a transcriptional regulator that plays a key role in the development of the kidneys...
  52. Hu Q, Gao F, Tian W, Ruteshouser E, Wang Y, Lazar A, et al. Wt1 ablation and Igf2 upregulation in mice result in Wilms tumors with elevated ERK1/2 phosphorylation. J Clin Invest. 2011;121:174-83 pubmed publisher
    ..Several genetic alterations have been identified in WT patients, including inactivating mutations in WT1 and loss of heterozygosity or loss of imprinting at 11p15, which results in biallelic expression of IGF2...
  53. Katz T, Singh M, Degenhardt K, RIVERA FELICIANO J, Johnson R, Epstein J, et al. Distinct compartments of the proepicardial organ give rise to coronary vascular endothelial cells. Dev Cell. 2012;22:639-50 pubmed publisher