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Role of the Wilms’ tumour transcription factor, Wt1, in blood vessel formation

  • Molecular and Genomic Physiology
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Abstract

Blood vessel formation is important for normal organ development and tumour growth. A highly specialised developmental program of vessel formation exists in the heart and is essential for normal cardiogenesis. From mouse models, it became clear that the Wilms’ tumour protein Wt1 is required for normal heart development. Originally identified as a tumour suppressor gene based on its mutational inactivation in Wilms’ tumour or nephroblastoma, Wt1 is nowadays recognised to have much broader functions in organogenesis and pathophysiology. The multiple tasks of Wt1 are not only limited to the kidney but involve the heart and vascular system as well. In this review, we focus on recent findings about the importance of Wt1 in heart and coronary vessel development and the identified molecular mechanisms. In addition, we discuss the implication of Wt1 in the vascular response to myocardial ischaemia and its oncogenic potential as a promoter of tumour angiogenesis.

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References

  1. Ahn A, Frishman WH, Gutwein A, Passeri J, Nelson M (2008) Therapeutic angiogenesis: a new treatment approach for ischemic heart disease—part I. Cardiol Rev 16:163–171

    Article  PubMed  Google Scholar 

  2. Armstrong JF, Pritchard-Jones K, Bickmore WA, Hastie ND, Bard JB (1993) The expression of the Wilms’ tumour gene, WT1, in the developing mammalian embryo. Mech Dev 40:85–97

    Article  PubMed  CAS  Google Scholar 

  3. Baird PN, Simmons PJ (1997) Expression of the Wilms’ tumor gene (WT1) in normal hemopoiesis. Exp Hematol 25:312–320

    PubMed  CAS  Google Scholar 

  4. Bruening W, Pelletier J (1996) A non-AUG translational initiation event generates novel WT1 isoforms. J Biol Chem 271:8646–8654

    Article  PubMed  CAS  Google Scholar 

  5. Cai CL, Martin JC, Sun Y, Cui L, Wang L, Ouyang K, Yang L, Bu L, Liang X, Zhang X, Stallcup WB, Denton CP, McCulloch A, Chen J, Evans SM (2008) A myocardial lineage derives from Tbx18 epicardial cells. Nature 454:104–108

    Article  PubMed  CAS  Google Scholar 

  6. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380:435–439

    Article  PubMed  CAS  Google Scholar 

  7. Carmeliet P (2005) Angiogenesis in life, disease and medicine. Nature 438:932–936

    Article  PubMed  CAS  Google Scholar 

  8. Carmona R, González-Iriarte M, Pérez-Pomares JM, Muñoz-Chápuli R (2001) Localization of the Wilm’s tumour protein WT1 in avian embryos. Cell Tissue Res 303:173–186

    Article  PubMed  CAS  Google Scholar 

  9. Cohen MM Jr (2006) Vascular update: morphogenesis, tumors, malformations, and molecular dimensions. Am J Med Genet A 140:2013–2038

    PubMed  Google Scholar 

  10. Cummins EP, Taylor CT (2005) Hypoxia-responsive transcription factors. Pflugers Arch 450:363–371

    Article  PubMed  CAS  Google Scholar 

  11. Davies JA, Ladomery M, Hohenstein P, Michael L, Shafe A, Spraggon L, Hastie N (2004) Development of an siRNA-based method for repressing specific genes in renal organ culture and its use to show that the Wt1 tumour suppressor is required for nephron differentiation. Hum Mol Genet 13:235–246

    Article  PubMed  CAS  Google Scholar 

  12. Dechant G (2001) Molecular interactions between neurotrophin receptors. Cell Tissue Res 305:229–238

    Article  PubMed  CAS  Google Scholar 

  13. Dettman RW, Denetclaw W Jr, Ordahl CP, Bristow J (1998) Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol 193:169–181

    Article  PubMed  CAS  Google Scholar 

  14. Donovan MJ, Lin MI, Wiegn P, Ringstedt T, Kraemer R, Hahn R, Wang S, Ibañez CF, Rafii S, Hempstead BL (2000) Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. Development 127:4531–4540

    PubMed  CAS  Google Scholar 

  15. Duband JL, Monier F, Delannet M, Newgreen D (1995) Epithelium–mesenchyme transition during neural crest development. Acta Anat (Basel) 154:63–78

    Article  CAS  Google Scholar 

  16. Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442

    Article  PubMed  CAS  Google Scholar 

  17. Fischer C, Schneider M, Carmeliet P (2006) Principles and therapeutic implications of angiogenesis, vasculogenesis and arteriogenesis. Handb Exp Pharmacol 176(Pt 2):157–212

    Article  PubMed  CAS  Google Scholar 

  18. Gao X, Chen X, Taglienti M, Rumballe B, Little MH, Kreidberg JA (2005) Angioblast-mesenchyme induction of early kidney development is mediated by Wt1 and Vegfa. Development 132:5437–5449

    Article  PubMed  CAS  Google Scholar 

  19. Gittenberger-de Groot AC, Vrancken Peeters MP, Mentink MM, Gourdie RG, Poelmann RE (1998) Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res 82:1043–1052

    PubMed  CAS  Google Scholar 

  20. Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE (1991) Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci USA 88:9618–9622

    Article  PubMed  CAS  Google Scholar 

  21. Hashiya N, Jo N, Aoki M, Matsumoto K, Nakamura T, Sato Y, Ogata N, Ogihara T, Kaneda Y, Morishita R (2004) In vivo evidence of angiogenesis induced by transcription factor Ets-1: Ets-1 is located upstream of angiogenesis cascade. Circulation 109:3035–3041

    Article  PubMed  CAS  Google Scholar 

  22. Heil M, Schaper W (2007) Insights into pathways of arteriogenesis. Curr Pharm Biotechnol 8:35–42

    Article  PubMed  CAS  Google Scholar 

  23. Hofer T, Wenger H, Gassmann M (2002) Oxygen sensing, HIF-1alpha stabilization and potential therapeutic strategies. Pflugers Arch 443:503–507

    Article  PubMed  CAS  Google Scholar 

  24. Hohenstein P, Hastie ND (2006) The many facets of the Wilms’ tumour gene, WT1. Hum Mol Genet 15(Spec No 2):R196–R201

    Article  PubMed  CAS  Google Scholar 

  25. Iwasaka C, Tanaka K, Abe M, Sato Y (1996) Ets-1 regulates angiogenesis by inducing the expression of urokinase-type plasminogen activator and matrix metalloproteinase-1 and the migration of vascular endothelial cells. J Cell Physiol 169:522–531

    Article  PubMed  CAS  Google Scholar 

  26. Jomgeow T, Oji Y, Tsuji N, Ikeda Y, Ito K, Tsuda A, Nakazawa T, Tatsumi N, Sakaguchi N, Takashima S, Shirakata T, Nishida S, Hosen N, Kawakami M, Tsuboi A, Oka Y, Itoh K, Sugiyama H (2006) Wilms’ tumor gene WT1 17AA(−)/KTS(−) isoform induces morphological changes and promotes cell migration and invasion in vitro. Cancer Sci 97:259–270

    Article  PubMed  CAS  Google Scholar 

  27. Kim HS, Kim MS, Hancock AL, Harper JC, Park JY, Poy G, Perantoni AO, Cam M, Malik K, Lee SB (2007) Identification of novel Wilms’ tumor suppressor gene target genes implicated in kidney development. J Biol Chem 282:16278–16287

    Article  PubMed  CAS  Google Scholar 

  28. Kirschner KM, Wagner N, Wagner KD, Wellmann S, Scholz H (2006) The Wilms tumor suppressor Wt1 promotes cell adhesion through transcriptional activation of the alpha4integrin gene. J Biol Chem 281:31930–31939

    Article  PubMed  CAS  Google Scholar 

  29. Kola I, Brookes S, Green AR, Garber R, Tymms M, Papas TS, Seth A (1993) The Ets1 transcription factor is widely expressed during murine embryo development and is associated with mesodermal cells involved in morphogenetic processes such as organ formation. Proc Natl Acad Sci USA 90:7588–7592

    Article  PubMed  CAS  Google Scholar 

  30. Komiyama M, Ito K, Shimada Y (1987) Origin and development of the epicardium in the mouse embryo. Anat Embryol (Berl) 176:183–189

    Article  CAS  Google Scholar 

  31. Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R (1993) WT-1 is required for early kidney development. Cell 74:679–691

    Article  PubMed  CAS  Google Scholar 

  32. Kuo CT, Morrisey EE, Anandappa R, Sigrist K, Lu MM, Parmacek MS, Soudais C, Leiden JM (1997) GATA4 transcription factor is required for ventral morphogenesis and heart tube formation. Genes Dev 11:1048–1060

    Article  PubMed  CAS  Google Scholar 

  33. Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595

    Article  PubMed  CAS  Google Scholar 

  34. Liao D, Johnson RS (2007) Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis Rev 26:281–290

    Article  PubMed  CAS  Google Scholar 

  35. Männer J (1992) The development of pericardial villi in the chick embryo. Anat Embryol (Berl) 186:379–385

    Google Scholar 

  36. Maurer U, Brieger J, Weidmann E, Mitrou PS, Hoelzer D, Bergmann L (1997) The Wilms’ tumor gene is expressed in a subset of CD34+ progenitors and downregulated early in the course of differentiation in vitro. Exp Hematol 25:945–950

    PubMed  CAS  Google Scholar 

  37. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399:271–275

    Article  PubMed  CAS  Google Scholar 

  38. Menssen HD, Renkl HJ, Entezami M, Thiel E (1997) Wilms’ tumor gene expression in human CD34+ hematopoietic progenitors during fetal development and early clonogenic growth. Blood 89:3486–3487

    PubMed  CAS  Google Scholar 

  39. Minchenko A, Bauer T, Salceda S, Caro J (1994) Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo. Lab Invest 71:374–379

    PubMed  CAS  Google Scholar 

  40. Mokrý J, Cízková D, Filip S, Ehrmann J, Osterreicher J, Kolár Z, English D (2004) Nestin expression by newly formed human blood vessels. Stem Cells Dev 13:658–664

    Article  PubMed  Google Scholar 

  41. Mokrý J, Nĕmecek S (1998) Immunohistochemical detection of intermediate filament nestin. Acta Medica (Hradec Kralove) 41:73–80

    Google Scholar 

  42. Mokry J, Pudil R, Ehrmann J, Cizkova D, Osterreicher J, Filip S, Kolar Z (2008) Re-expression of nestin in the myocardium of postinfarcted patients. Virchows Arch 453:33–41

    Article  PubMed  CAS  Google Scholar 

  43. Molkentin JD, Lin Q, Duncan SA, Olson EN (1997) Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev 11:1061–1072

    Article  PubMed  CAS  Google Scholar 

  44. Moore AW, McInnes L, Kreidberg J, Hastie ND, Schedl A (1999) YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis. Development 126:1845–1857

    PubMed  CAS  Google Scholar 

  45. Moore AW, Schedl A, McInnes L, Doyle M, Hecksher-Sorensen J, Hastie ND (1998) YAC transgenic analysis reveals Wilms’ tumour 1 gene activity in the proliferating coelomic epithelium, developing diaphragm and limb. Mech Dev 79:169–184

    Article  PubMed  CAS  Google Scholar 

  46. Morishita R, Aoki M, Hashiya N, Makino H, Yamasaki K, Azuma J, Sawa Y, Matsuda H, Kaneda Y, Ogihara T (2004) Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease. Hypertension 44:203–209

    Article  PubMed  CAS  Google Scholar 

  47. Morrison AA, Viney RL, Ladomery MR (2008) The post-transcriptional roles of WT1, a multifunctional zinc-finger protein. Biochim Biophys Acta 1785:55–62

    PubMed  CAS  Google Scholar 

  48. Morrison AA, Viney RL, Saleem MA, Ladomery MR (2008) New insights into the function of the Wilms tumor suppressor gene WT1 in podocytes. Am J Physiol Renal Physiol 295:F12–F17

    Article  PubMed  CAS  Google Scholar 

  49. Muñoz-Chápuli R, Pérez-Pomares JM, Macías D, García-Garrido L, Carmona R, González-Iriarte M (2001) The epicardium as a source of mesenchyme for the developing heart. Ital J Anat Embryol 106:187–196

    PubMed  Google Scholar 

  50. Oikawa M, Abe M, Kurosawa H, Hida W, Shirato K, Sato Y (2001) Hypoxia induces transcription factor ETS-1 via the activity of hypoxia-inducible factor-1. Biochem Biophys Res Commun 289:39–43

    Article  PubMed  CAS  Google Scholar 

  51. Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, Houghton DC, Junien C, Habib R, Fouser L et al (1991) Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys–Drash syndrome. Cell 67:437–447

    Article  PubMed  CAS  Google Scholar 

  52. Pelosi E, Valtieri M, Coppola S, Botta R, Gabbianelli M, Lulli V, Marziali G, Masella B, Müller R, Sgadari C, Testa U, Bonanno G, Peschle C (2002) Identification of the hemangioblast in postnatal life. Blood 100:3203–3208

    Article  PubMed  CAS  Google Scholar 

  53. Pérez-Pomares JM, Carmona R, González-Iriarte M, Atencia G, Wessels A, Muñoz-Chápuli R (2002) Origin of coronary endothelial cells from epicardial mesothelium in avian embryos. Int J Dev Biol 46:1005–1013

    PubMed  Google Scholar 

  54. Poelmann RE, Gittenberger-de Groot AC, Mentink MM, Bökenkamp R, Hogers B (1993) Development of the cardiac coronary vascular endothelium, studied with antiendothelial antibodies, in chicken-quail chimeras. Circ Res 73:559–568

    PubMed  CAS  Google Scholar 

  55. Pritchard-Jones K, Fleming S, Davidson D, Bickmore W, Porteous D, Gosden C, Bard J, Buckler A, Pelletier J, Housman D et al (1990) The candidate Wilms’ tumour gene is involved in genitourinary development. Nature 346:194–197

    Article  PubMed  CAS  Google Scholar 

  56. Rackley RR, Flenniken AM, Kuriyan NP, Kessler PM, Stoler MH, Williams BR (1993) Expression of the Wilms’ tumor suppressor gene WT1 during mouse embryogenesis. Cell Growth Differ 4:1023–1031

    PubMed  CAS  Google Scholar 

  57. Rao MK, Pham J, Imam JS, MacLean JA, Murali D, Furuta Y, Sinha-Hikim AP, Wilkinson MF (2006) Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis. Genes Dev 20:147–152

    Article  PubMed  CAS  Google Scholar 

  58. Ratajska A, Czarnowska E, Ciszek B (2008) Embryonic development of the proepicardium and coronary vessels. Int J Dev Biol 52:229–236

    Article  PubMed  Google Scholar 

  59. Rivera MN, Haber DA (2005) Wilms’ tumour: connecting tumorigenesis and organ development in the kidney. Nat Rev Cancer 5:699–712

    Article  PubMed  CAS  Google Scholar 

  60. Roberts SG (2005) Transcriptional regulation by WT1 in development. Curr Opin Genet Dev 15:542–547

    Article  PubMed  CAS  Google Scholar 

  61. Romano LA, Runyan RB (1999) Slug is a mediator of epithelial–mesenchymal cell transformation in the developing chicken heart. Dev Biol 212:243–254

    Article  PubMed  CAS  Google Scholar 

  62. Salceda S, Caro J (1997) Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin–proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem 272:22642–22647

    Article  PubMed  CAS  Google Scholar 

  63. Schulte I, Schlueter J, Abu-Issa R, Brand T, Männer J (2007) Morphological and molecular left-right asymmetries in the development of the proepicardium: a comparative analysis on mouse and chick embryos. Dev Dyn 236:684–695

    Article  PubMed  Google Scholar 

  64. Semenza GL (2003) Angiogenesis in ischemic and neoplastic disorders. Annu Rev Med 54:17–28

    Article  PubMed  CAS  Google Scholar 

  65. Semenza GL (2007) Vasculogenesis, angiogenesis, and arteriogenesis: mechanisms of blood vessel formation and remodeling. J Cell Biochem 102:840–847

    Article  PubMed  CAS  Google Scholar 

  66. Sharma PM, Bowman M, Madden SL, Rauscher FJ 3rd, Sukumar S (1994) RNA editing in the Wilms’ tumor susceptibility gene, WT1. Genes Dev 8:720–731

    Article  PubMed  CAS  Google Scholar 

  67. Shi Q, Rafii S, Wu MH, Wijelath ES, Yu C, Ishida A, Fujita Y, Kothari S, Mohle R, Sauvage LR, Moore MA, Storb RF, Hammond WP (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92:362–367

    PubMed  CAS  Google Scholar 

  68. Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845

    Article  PubMed  CAS  Google Scholar 

  69. Smolen GA, Vassileva MT, Wells J, Matunis MJ, Haber DA (2004) SUMO-1 modification of the Wilms’ tumor suppressor WT1. Cancer Res 64:7846–7851

    Article  PubMed  CAS  Google Scholar 

  70. Timár J, Mészáros L, Orosz Z, Albini A, Rásó E (2005) WT1 expression in angiogenic tumours of the skin. Histopathology 47:67–73

    Article  PubMed  Google Scholar 

  71. Tjwa M, Luttun A, Autiero M, Carmeliet P (2003) VEGF and PlGF: two pleiotropic growth factors with distinct roles in development and homeostasis. Cell Tissue Res 314:5–14

    Article  PubMed  CAS  Google Scholar 

  72. Viney RL, Morrison AA, van den Heuvel LP, Ni L, Mathieson PW, Saleem MA, Ladomery MR (2007) A proteomic investigation of glomerular podocytes from a Denys–Drash syndrome patient with a mutation in the Wilms tumour suppressor gene WT1. Proteomics 7:804–815

    Article  PubMed  CAS  Google Scholar 

  73. Virágh S, Challice CE (1981) The origin of the epicardium and the embryonic myocardial circulation in the mouse. Anat Rec 201:157–168

    Article  PubMed  Google Scholar 

  74. Vrancken Peeters MP, Gittenberger-de Groot AC, Mentink MM, Poelmann RE (1999) Smooth muscle cells and fibroblasts of the coronary arteries derive from epithelial–mesenchymal transformation of the epicardium. Anat Embryol (Berl) 199:367–378

    Article  CAS  Google Scholar 

  75. Wagner KD, Wagner N, Bondke A, Nafz B, Flemming B, Theres H, Scholz H (2002) The Wilms’ tumor suppressor Wt1 is expressed in the coronary vasculature after myocardial infarction. FASEB J 16:1117–1119

    PubMed  CAS  Google Scholar 

  76. Wagner KD, Wagner N, Vidal VP, Schley G, Wilhelm D, Schedl A, Englert C, Scholz H (2002) The Wilms’ tumor gene Wt1 is required for normal development of the retina. EMBO J 21:1398–1405

    Article  PubMed  CAS  Google Scholar 

  77. Wagner KD, Wagner N, Wellmann S, Schley G, Bondke A, Theres H, Scholz H (2003) Oxygen-regulated expression of the Wilms’ tumor suppressor Wt1 involves hypoxia-inducible factor-1 (HIF-1). FASEB J 17:1364–1366

    PubMed  CAS  Google Scholar 

  78. Wagner N, Michiels JF, Schedl A, Wagner KD (2008) The Wilms’ tumour suppressor WT1 is involved in endothelial cell proliferation and migration: expression in tumour vessels in vivo. Oncogene 27:3662–3672

    Article  PubMed  CAS  Google Scholar 

  79. Wagner N, Panelos J, Massi D, Wagner KD (2008) The Wilms’ tumor suppressor WT1 is associated with melanoma proliferation. Pflugers Arch 455:839–847

    Article  PubMed  CAS  Google Scholar 

  80. Wagner N, Wagner KD, Hammes A, Kirschner KM, Vidal VP, Schedl A, Scholz H (2005) A splice variant of the Wilms’ tumour suppressor Wt1 is required for normal development of the olfactory system. Development 132:1327–1336

    Article  PubMed  CAS  Google Scholar 

  81. Wagner N, Wagner KD, Scholz H, Kirschner KM, Schedl A (2006) Intermediate filament protein nestin is expressed in developing kidney and heart and might be regulated by the Wilms’ tumor suppressor Wt1. Am J Physiol Regul Integr Comp Physiol 291:R779–R787

    PubMed  CAS  Google Scholar 

  82. Wagner N, Wagner KD, Theres H, Englert C, Schedl A, Scholz H (2005) Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms’ tumor transcription factor Wt1. Genes Dev 19:2631–4226

    Article  PubMed  CAS  Google Scholar 

  83. Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92:5510–5514

    Article  PubMed  CAS  Google Scholar 

  84. Wang GL, Semenza GL (1995) Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270:1230–1237

    Article  PubMed  CAS  Google Scholar 

  85. Watt AJ, Battle MA, Li J, Duncan SA (2004) GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc Natl Acad Sci USA 101:12573–12578

    Article  PubMed  CAS  Google Scholar 

  86. Wilm B, Ipenberg A, Hastie ND, Burch JB, Bader DM (2005) The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development 132:5317–5328

    Article  PubMed  CAS  Google Scholar 

  87. Yang JT, Rayburn H, Hynes RO (1995) Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development. Development 121:549–560

    PubMed  CAS  Google Scholar 

  88. Ye Y, Raychaudhuri B, Gurney A, Campbell CE, Williams BR (1996) Regulation of WT1 by phosphorylation: inhibition of DNA binding, alteration of transcriptional activity and cellular translocation. EMBO J 15:5606–5615

    PubMed  CAS  Google Scholar 

  89. Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT (2008) Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454:109–113

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The work was supported by grants to K.D.W. from Fondation Recherche Medicale, Fondation Cœur et Artères, and Association pour la Recherche sur le Cancer and Fondation Cœur et Artères. N.W. was the recipient of a fellowship from the Fondation de France. H.S. appreciates the continued support of his work by the Deutsche Forschungsgemeinschaft. We apologise to those colleagues whose original contributions could not be cited in this article due to space constraints.

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  1. Institut für Vegetative Physiologie, Charité–Universitätsmedizin Berlin, Tucholskystraße 2, 10117, Berlin, Germany

    Holger Scholz

  2. INSERM U907, Nice, France

    Kay-Dietrich Wagner & Nicole Wagner

  3. Faculté de Médecine, Université de Nice-Sophia Antipolis, Nice, France

    Kay-Dietrich Wagner & Nicole Wagner

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  1. Holger Scholz
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Correspondence to Holger Scholz.

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Scholz, H., Wagner, KD. & Wagner, N. Role of the Wilms’ tumour transcription factor, Wt1, in blood vessel formation. Pflugers Arch - Eur J Physiol 458, 315–323 (2009). https://doi.org/10.1007/s00424-008-0621-3

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