Wnt4

Summary

Gene Symbol: Wnt4
Description: wingless-type MMTV integration site family, member 4
Alias: Wnt-4, protein Wnt-4, signal molecule, wingless-related MMTV integration site 4
Species: mouse
Products:     Wnt4

Top Publications

  1. Perantoni A, Timofeeva O, Naillat F, Richman C, Pajni Underwood S, Wilson C, et al. Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development. Development. 2005;132:3859-71 pubmed
    ..Prior to mutant morphological changes, Wnt4 and Lim1 expression, which is essential for nephrogenesis, is absent in MM...
  2. Park J, Ma W, O Brien L, Chung E, Guo J, Cheng J, et al. Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev Cell. 2012;23:637-51 pubmed publisher
    ..b>Wnt4 and Fgf8 are essential for progenitor commitment; cis-regulatory modules flanking each gene are cobound by Six2 and ..
  3. Louis I, Heinonen K, Chagraoui J, Vainio S, Sauvageau G, Perreault C. The signaling protein Wnt4 enhances thymopoiesis and expands multipotent hematopoietic progenitors through beta-catenin-independent signaling. Immunity. 2008;29:57-67 pubmed publisher
    ..Using gain-of-function and loss-of-function models, we found that Wnt4 differentially affected diverse subsets of hematopoietic stem and progenitor cells...
  4. Ottolenghi C, Omari S, Garcia Ortiz J, Uda M, Crisponi L, Forabosco A, et al. Foxl2 is required for commitment to ovary differentiation. Hum Mol Genet. 2005;14:2053-62 pubmed
    ..This suggests the possible continued involvement of sex-determining genes in maintaining ovarian function throughout female reproductive life. ..
  5. Heikkilä M, Prunskaite R, Naillat F, Itäranta P, Vuoristo J, Leppäluoto J, et al. The partial female to male sex reversal in Wnt-4-deficient females involves induced expression of testosterone biosynthetic genes and testosterone production, and depends on androgen action. Endocrinology. 2005;146:4016-23 pubmed
    ..These data imply that Wnt-4 signaling normally acts to suppress testosterone biosynthesis in the female, and that testosterone is the putative mediator of the masculinization phenotype in Wnt-4-deficient females. ..
  6. Chassot A, Ranc F, Gregoire E, Roepers Gajadien H, Taketo M, Camerino G, et al. Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet. 2008;17:1264-77 pubmed publisher
    ..Molecular analyses demonstrate an absence of female-specific activation of Wnt4 and as a consequence XY-like vascularization and steroidogenesis...
  7. 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. ..
  8. 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 ..
  9. Nef S, Verma Kurvari S, Merenmies J, Vassalli J, Efstratiadis A, Accili D, et al. Testis determination requires insulin receptor family function in mice. Nature. 2003;426:291-5 pubmed
    ..Reduced expression of both Sry and the early testis-specific marker Sox9 indicates that the insulin signalling pathway is required for male sex determination. ..
  10. Agalliu D, Takada S, Agalliu I, McMahon A, Jessell T. Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron. 2009;61:708-20 pubmed publisher
    ..show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate...

Detail Information

Publications62

  1. Perantoni A, Timofeeva O, Naillat F, Richman C, Pajni Underwood S, Wilson C, et al. Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development. Development. 2005;132:3859-71 pubmed
    ..Prior to mutant morphological changes, Wnt4 and Lim1 expression, which is essential for nephrogenesis, is absent in MM...
  2. Park J, Ma W, O Brien L, Chung E, Guo J, Cheng J, et al. Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev Cell. 2012;23:637-51 pubmed publisher
    ..b>Wnt4 and Fgf8 are essential for progenitor commitment; cis-regulatory modules flanking each gene are cobound by Six2 and ..
  3. Louis I, Heinonen K, Chagraoui J, Vainio S, Sauvageau G, Perreault C. The signaling protein Wnt4 enhances thymopoiesis and expands multipotent hematopoietic progenitors through beta-catenin-independent signaling. Immunity. 2008;29:57-67 pubmed publisher
    ..Using gain-of-function and loss-of-function models, we found that Wnt4 differentially affected diverse subsets of hematopoietic stem and progenitor cells...
  4. Ottolenghi C, Omari S, Garcia Ortiz J, Uda M, Crisponi L, Forabosco A, et al. Foxl2 is required for commitment to ovary differentiation. Hum Mol Genet. 2005;14:2053-62 pubmed
    ..This suggests the possible continued involvement of sex-determining genes in maintaining ovarian function throughout female reproductive life. ..
  5. Heikkilä M, Prunskaite R, Naillat F, Itäranta P, Vuoristo J, Leppäluoto J, et al. The partial female to male sex reversal in Wnt-4-deficient females involves induced expression of testosterone biosynthetic genes and testosterone production, and depends on androgen action. Endocrinology. 2005;146:4016-23 pubmed
    ..These data imply that Wnt-4 signaling normally acts to suppress testosterone biosynthesis in the female, and that testosterone is the putative mediator of the masculinization phenotype in Wnt-4-deficient females. ..
  6. Chassot A, Ranc F, Gregoire E, Roepers Gajadien H, Taketo M, Camerino G, et al. Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet. 2008;17:1264-77 pubmed publisher
    ..Molecular analyses demonstrate an absence of female-specific activation of Wnt4 and as a consequence XY-like vascularization and steroidogenesis...
  7. 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. ..
  8. 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 ..
  9. Nef S, Verma Kurvari S, Merenmies J, Vassalli J, Efstratiadis A, Accili D, et al. Testis determination requires insulin receptor family function in mice. Nature. 2003;426:291-5 pubmed
    ..Reduced expression of both Sry and the early testis-specific marker Sox9 indicates that the insulin signalling pathway is required for male sex determination. ..
  10. Agalliu D, Takada S, Agalliu I, McMahon A, Jessell T. Motor neurons with axial muscle projections specified by Wnt4/5 signaling. Neuron. 2009;61:708-20 pubmed publisher
    ..show that the specification of MMC fate involves a dorsoventral signaling program mediated by three Wnt proteins (Wnt4, Wnt5a, and Wnt5b) expressed in and around the floor plate...
  11. Bogani D, Siggers P, Brixey R, Warr N, Beddow S, Edwards J, et al. Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4) reveals a requirement for MAPK signalling in mouse sex determination. PLoS Biol. 2009;7:e1000196 pubmed publisher
  12. Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier M, et al. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol. 2006;4:e187 pubmed
    ..In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex determination...
  13. Ikegawa M, Han H, Okamoto A, Matsui R, Tanaka M, Omi N, et al. Syndactyly and preaxial synpolydactyly in the single Sfrp2 deleted mutant mice. Dev Dyn. 2008;237:2506-17 pubmed publisher
    ..Although joint formation was not disrupted, chondrocyte maturation was preaxially disturbed. Our results suggest that the Sfrp2 deleted mice can be a useful animal model to study human syndactyly/preaxial synpolydactyly defects...
  14. DeFalco T, Takahashi S, Capel B. Two distinct origins for Leydig cell progenitors in the fetal testis. Dev Biol. 2011;352:14-26 pubmed publisher
    ..This study highlights the cellular diversity of the interstitial cell population and suggests that complex cell-cell interactions among cells in the interstitium are involved in testis morphogenesis...
  15. Boyle S, Kim M, Valerius M, McMahon A, Kopan R. Notch pathway activation can replace the requirement for Wnt4 and Wnt9b in mesenchymal-to-epithelial transition of nephron stem cells. Development. 2011;138:4245-54 pubmed publisher
    ..Induction by Wnt9b directs cells to exit the stem cell niche and express Wnt4, which is both necessary and sufficient for the formation of epithelia...
  16. Chi L, Itäranta P, Zhang S, Vainio S. Sprouty2 is involved in male sex organogenesis by controlling fibroblast growth factor 9-induced mesonephric cell migration to the developing testis. Endocrinology. 2006;147:3777-88 pubmed
    ..Based on these data, we propose that the Sprouty proteins are involved normally in mediating the sexually dimorphic signaling of FGF9 and controlling cell migration from the mesonephros during testis development. ..
  17. 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. ..
  18. 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...
  19. Jeays Ward K, Dandonneau M, Swain A. Wnt4 is required for proper male as well as female sexual development. Dev Biol. 2004;276:431-40 pubmed
    ..The signaling molecule WNT4 has been shown to be important in female sexual development...
  20. 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. ..
  21. Jeays Ward K, Hoyle C, Brennan J, Dandonneau M, Alldus G, Capel B, et al. Endothelial and steroidogenic cell migration are regulated by WNT4 in the developing mammalian gonad. Development. 2003;130:3663-70 pubmed
    The signalling molecule WNT4 has been associated with sex reversal phenotypes in mammals. Here we show that the role of WNT4 in gonad development is to pattern the sex-specific vasculature and to regulate steroidogenic cell recruitment...
  22. Kispert A, Vainio S, Shen L, Rowitch D, McMahon A. Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips. Development. 1996;122:3627-37 pubmed
    ..We suggest that Wnt-11 acts as an autocrine factor within the ureter epithelium and that its expression is regulated at least in part by proteoglycans. ..
  23. Kiefer S, Robbins L, Rauchman M. Conditional expression of Wnt9b in Six2-positive cells disrupts stomach and kidney function. PLoS ONE. 2012;7:e43098 pubmed publisher
    ..These results demonstrate that expression of Wnt9b in Six2-positive cells disrupts cell fate decisions in the kidney and the gastrointestinal tract...
  24. Kimura T, Nakamura T, Murayama K, Umehara H, Yamano N, Watanabe S, et al. The stabilization of beta-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression. Dev Biol. 2006;300:545-53 pubmed
    ..Our results show that the suppression of Wnt/beta-catenin signaling is a prerequisite for the normal development of PGCs. ..
  25. Bagheri Fam S, Sim H, Bernard P, Jayakody I, Taketo M, Scherer G, et al. Loss of Fgfr2 leads to partial XY sex reversal. Dev Biol. 2008;314:71-83 pubmed
    ..In summary, we provide evidence that FGFR2 is important for male sex determination in mice, thereby rendering human FGFR2 a candidate gene for unsolved DSD cases such as 10q26 deletions. ..
  26. 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. ..
  27. 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
    ..In the absence of FGF8 signaling, nephron formation is initiated, but the nascent nephrons do not express Wnt4 or Lim1, and nephrogenesis does not progress to the S-shaped body stage...
  28. Heinonen K, Vanegas J, Brochu S, Shan J, Vainio S, Perreault C. Wnt4 regulates thymic cellularity through the expansion of thymic epithelial cells and early thymic progenitors. Blood. 2011;118:5163-73 pubmed publisher
    ..previously that posthematopoietic cell transplantation thymic function was improved by retroviral overexpression of Wnt4 in donor hematopoietic cells...
  29. Devgan V, Mammucari C, Millar S, Brisken C, Dotto G. p21WAF1/Cip1 is a negative transcriptional regulator of Wnt4 expression downstream of Notch1 activation. Genes Dev. 2005;19:1485-95 pubmed
    ..More specifically, expression of the Wnt4 gene is under negative control of endogenous p21 both in vitro and in vivo...
  30. Lyuksyutova A, Lu C, Milanesio N, King L, Guo N, Wang Y, et al. Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science. 2003;302:1984-8 pubmed
    ..We found that Wnt4 messenger RNA is expressed in a decreasing anterior-to-posterior gradient in the floor plate, and that a directed ..
  31. Park J, Valerius M, McMahon A. Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development. Development. 2007;134:2533-9 pubmed
    ..Several lines of evidence support the sequential roles of two Wnt family members, Wnt9b and Wnt4, in renal vesicle induction...
  32. Cui S, Ross A, Stallings N, Parker K, Capel B, Quaggin S. Disrupted gonadogenesis and male-to-female sex reversal in Pod1 knockout mice. Development. 2004;131:4095-105 pubmed
    ..Our results establish that Pod1 is essential for gonadal development, and place it in a transcriptional network that orchestrates cell fate decisions in gonadal progenitors. ..
  33. 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
    ..Wnt9b acts upstream of another Wnt, Wnt4, in this process, and our data implicate canonical Wnt signaling as one of the major pathways in the organization ..
  34. Dudley A, Lyons K, Robertson E. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev. 1995;9:2795-807 pubmed
    ..Consequently, homozygous mutant animals exhibit renal dysplasia and anophthalmia at birth. Overall, these findings identify BMP-7 as an essential signaling molecule during mammalian kidney and eye development. ..
  35. Kato M, Patel M, Levasseur R, Lobov I, Chang B, Glass D, et al. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol. 2002;157:303-14 pubmed
    ..Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation. ..
  36. Shan J, Jokela T, Skovorodkin I, Vainio S. Mapping of the fate of cell lineages generated from cells that express the Wnt4 gene by time-lapse during kidney development. Differentiation. 2010;79:57-64 pubmed publisher
    The Wnt4 gene encodes a secreted signaling molecule controlling the development of several organs, such as the kidney, adrenal gland, ovary, mammary gland and pituitary gland...
  37. Michos O, Panman L, Vintersten K, Beier K, Zeller R, Zuniga A. Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development. 2004;131:3401-10 pubmed
    ..As a consequence, the metanephric mesenchyme is eliminated by apoptosis, in the same way as the core mesenchymal cells of the limb bud. ..
  38. Guo X, Day T, Jiang X, Garrett Beal L, Topol L, Yang Y. Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation. Genes Dev. 2004;18:2404-17 pubmed
    ..We have found that several Wnt genes, including Wnt4, Wnt14, and Wnt16, were expressed in overlapping and complementary patterns in the developing synovial joints, ..
  39. Tomizuka K, Horikoshi K, Kitada R, Sugawara Y, Iba Y, Kojima A, et al. R-spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling. Hum Mol Genet. 2008;17:1278-91 pubmed publisher
  40. 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. ..
  41. Surendran K, Simon T. CNP gene expression is activated by Wnt signaling and correlates with Wnt4 expression during renal injury. Am J Physiol Renal Physiol. 2003;284:F653-62 pubmed
    ..Induction of Nppc occurred in identical cell populations to those in which Wnt4 is induced after renal injury. In addition, Nppc was activated in Wnt4-expressing cells during nephrogenesis...
  42. Warr N, Bogani D, Siggers P, Brixey R, Tateossian H, Dopplapudi A, et al. Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1. PLoS ONE. 2011;6:e19572 pubmed publisher
    ..Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans. ..
  43. Surendran K, McCaul S, Simon T. A role for Wnt-4 in renal fibrosis. Am J Physiol Renal Physiol. 2002;282:F431-41 pubmed
    ..b>Wnt4 expression is induced throughout the collecting ducts in four murine models of renal injury that produce ..
  44. Uhlenhaut N, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, et al. Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell. 2009;139:1130-42 pubmed publisher
    ..They might also have important medical implications for the understanding and treatment of some disorders of sexual development in children and premature menopause in women. ..
  45. Warr N, Carré G, Siggers P, Faleato J, Brixey R, Pope M, et al. Gadd45? and Map3k4 interactions regulate mouse testis determination via p38 MAPK-mediated control of Sry expression. Dev Cell. 2012;23:1020-31 pubmed publisher
    ..Taken together, our data suggest a requirement for GADD45? in promoting MAP3K4-mediated activation of p38 MAPK signaling in embryonic gonadal somatic cells for testis determination in the mouse. ..
  46. Boyer A, Lapointe E, Zheng X, Cowan R, Li H, Quirk S, et al. WNT4 is required for normal ovarian follicle development and female fertility. FASEB J. 2010;24:3010-25 pubmed publisher
    To study the role of WNT4 in the postnatal ovary, a mouse strain bearing a floxed Wnt4 allele was created and mated to the Amhr2(tm3(cre)Bhr) strain to target deletion of Wnt4 to granulosa cells...
  47. Kobayashi A, Kwan K, Carroll T, McMahon A, Mendelsohn C, Behringer R. Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development. 2005;132:2809-23 pubmed
    ..We also demonstrate that the nephric duct is essential for the elongation and maintenance of the adjacent Mullerian duct, the anlage of the female reproductive tract. ..
  48. 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. ..
  49. Kahn J, Shwartz Y, Blitz E, Krief S, Sharir A, Breitel D, et al. Muscle contraction is necessary to maintain joint progenitor cell fate. Dev Cell. 2009;16:734-43 pubmed publisher
    ..In conclusion, our findings provide the missing link between progenitor cell fate determination and embryonic movement, two processes shown to be essential for correct organogenesis. ..
  50. 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
    ..A (CSA), an inhibitor of Calcium/NFAT signalling, decreases nephron formation--a phenotype similar to that in Wnt4(-/-) embryos...
  51. Yao H, Aardema J, Holthusen K. Sexually dimorphic regulation of inhibin beta B in establishing gonadal vasculature in mice. Biol Reprod. 2006;74:978-83 pubmed
    ..On the other hand, in the ovary, inhibin beta B is repressed by WNT4 and its downstream target follistatin, leading to the absence of the coelomic vessel...
  52. Capel B. The battle of the sexes. Mech Dev. 2000;92:89-103 pubmed
  53. Barrionuevo F, Bagheri Fam S, Klattig J, Kist R, Taketo M, Englert C, et al. Homozygous inactivation of Sox9 causes complete XY sex reversal in mice. Biol Reprod. 2006;74:195-201 pubmed
    ..5 reveals immediate, complete sex reversal, as shown by expression of the early ovary-specific markers Wnt4 and Foxl2 and by lack of testis cord and Leydig cell formation...
  54. 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...
  55. Karner C, 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 pubmed publisher
    ..These findings provide novel insights into the molecular mechanisms that regulate progenitor cell differentiation during normal and pathological conditions. ..
  56. Heinonen K, Vanegas J, Lew D, Krosl J, Perreault C. Wnt4 enhances murine hematopoietic progenitor cell expansion through a planar cell polarity-like pathway. PLoS ONE. 2011;6:e19279 pubmed publisher
    ..b>Wnt4 is one of the Wnt proteins that can elicit non-canonical pathways...
  57. 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
    ..enzymes (p450scc, 3betaHSD and p450c17) were not expressed in XY Fog2(-/-) and Gata(ki/ki) gonads, whereas Wnt4, a gene required for normal ovarian development, was expressed ectopically...
  58. Jordan B, Mohammed M, Ching S, Delot E, Chen X, Dewing P, et al. Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans. Am J Hum Genet. 2001;68:1102-9 pubmed
    ..These observations suggest that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway. ..
  59. Kobayashi A, Valerius M, Mugford J, Carroll T, Self M, Oliver G, et al. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell. 2008;3:169-81 pubmed publisher
    ..Taken together, our observations suggest that Six2 activity cell-autonomously regulates a multipotent nephron progenitor population. ..
  60. Levinson R, Batourina E, Choi C, Vorontchikhina M, Kitajewski J, Mendelsohn C. Foxd1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development. 2005;132:529-39 pubmed
  61. Naillat F, Prunskaite Hyyryläinen R, Pietilä I, Sormunen R, Jokela T, Shan J, et al. Wnt4/5a signalling coordinates cell adhesion and entry into meiosis during presumptive ovarian follicle development. Hum Mol Genet. 2010;19:1539-50 pubmed publisher
    ..These findings indicate a critical role for Wnt signalling in meiosis. Thus, the Wnt signals are important somatic cell signals that coordinate presumptive female follicle development. ..
  62. 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. ..