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Genetic and developmental basis for urinary tract obstruction

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Abstract

Urinary tract obstruction results in obstructive nephropathy and uropathy. It is the most frequent cause of renal failure in infants and children. In the past two decades studies of transgenic models and humans have greatly enhanced our understanding of the genetic factors and developmental processes important in urinary tract obstruction. The emerging picture is that development of the urinary tract requires precise integration of a variety of progenitor cell populations of different embryonic origins. Such integration is controlled by an intricate signaling network that undergoes dynamic changes as the embryo develops. Most congenital forms of urinary tract obstruction result from the disruption of diverse factors and genetic pathways involved in these processes, especially in the morphogenesis of the urinary conduit or the functional aspects of the pyeloureteral peristaltic machinery.

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References

  1. Chevalier RL, Peters CA (2003) Congenital urinary tract obstruction: Proceedings of the State-Of-The-Art Strategic Planning Workshop—National Institutes of Health, Bethesda, Maryland, USA, 11–12 March 2002. Pediatr Nephrol 18:576–606

    PubMed  Google Scholar 

  2. Chevalier RL (1999) Molecular and cellular pathophysiology of obstructive nephropathy. Pediatr Nephrol 13:612–619

    CAS  PubMed  Google Scholar 

  3. Chevalier RL (1998) Pathophysiology of obstructive nephropathy in the newborn. Semin Nephrol 18:585–593

    CAS  PubMed  Google Scholar 

  4. Chang CP, McDill BW, Neilson JR, Joist HE, Epstein JA, Crabtree GR, Chen F (2004) Calcineurin is required in urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery. J Clin Invest 113:1051–1058

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Mendelsohn C (2004) Functional obstruction: the renal pelvis rules. J Clin Invest 113:957–959

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Bascands JL, Schanstra JP (2005) Obstructive nephropathy: insights from genetically engineered animals. Kidney Int 68:925–937

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Chevalier RL (2004) Promise for gene therapy in obstructive nephropathy. Kidney Int 66:1709–1710

    CAS  PubMed  Google Scholar 

  8. Peters CA (2005) Congenital obstructive nephropathy: is the fog lifting? Kidney Int 67:371–372

    PubMed  Google Scholar 

  9. Liapis H (2003) Biology of congenital obstructive nephropathy. Nephron Exp Nephrol 93:e87–e91

    CAS  PubMed  Google Scholar 

  10. Klahr S, Morrissey J (2002) Obstructive nephropathy and renal fibrosis. Am J Physiol Renal Physiol 283:F861–F875

    PubMed  Google Scholar 

  11. Chevalier RL (2002) Obstructive uropathy: state of the art. Pediatr Med Chir 24:95–97

    CAS  PubMed  Google Scholar 

  12. Kenda RB, Kenig T, Budihna N (1991) Detecting vesico-ureteral reflux in asymptomatic siblings of children with reflux by direct radionuclide cystography. Eur J Pediatr 150:735–737

    CAS  Google Scholar 

  13. Feather SA, Malcolm S, Woolf AS, Wright V, Blayton D, Reid CJ, Flinter FA, Proesmans W, Devriendt K, Carter J, Warwicker P, Goodship TH, Goodship JA (2000) Primary, nonsyndromic vesicoureteric reflux and its nephropathy is genetically heterogeneous, with a locus on chromosome 1. Am J Hum Genet 66:1420–1425

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Queisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger J (2002) Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990–1998). Arch Gynecol Obstet 266:163–167

    CAS  PubMed  Google Scholar 

  15. Schedl A (2007) Renal abnormalities and their developmental origin. Nat Rev Genet 8:791–802

    CAS  PubMed  Google Scholar 

  16. Dressler GR (2006) The cellular basis of kidney development. Annu Rev Cell Dev Biol 22:509–529

    CAS  PubMed  Google Scholar 

  17. 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

    CAS  Google Scholar 

  18. Xu PX, Adams J, Peters H, Brown MC, Heaney S, Maas R (1999) Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet 23:113–117

    CAS  PubMed  Google Scholar 

  19. Wellik DM, Hawkes PJ, Capecchi MR (2002) Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev 16:1423–1432

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Xu PX, Zheng W, Huang L, Marie P, Laclef DL (2003) Six1 is required for the early organogenesis of mammalian kidney. Development 130:3085–3094

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Nishinakamura R, Matsumoto Y, Nakao K, Nakamura K, Sato A, Copeland NG, Gilbert DJ, Jenkins NA, Scully S, Lacey DL, Katsuki M, Asashima M, Yokota T (2001) Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development 128:3105–3115

    CAS  PubMed  Google Scholar 

  22. Sajithlal G, Zou D, Silvius D, Xu PX (2005) Eya 1 acts as a critical regulator for specifying the metanephric mesenchyme. Dev Biol 284:323–336

    CAS  PubMed  Google Scholar 

  23. Wilm B, James RG, Schultheiss TM, Hogan BL (2004) The forkhead genes, Foxc1 and Foxc2, regulate paraxial versus intermediate mesoderm cell fate. Dev Biol 271:176–189

    CAS  PubMed  Google Scholar 

  24. Grieshammer U, Le M, Plump AS, Wang F (2004) SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev Cell 6:709–717

    CAS  PubMed  Google Scholar 

  25. Shakya R, Jho EH, Kotka P, Wu Z, Kholodilv N, Burke R, D’Agati V, Constantini F (2005) The role of GDNF in patterning the excretory system. Dev Biol 283:70–84

    CAS  PubMed  Google Scholar 

  26. Maeshima A, Sakurai H, Choi Y, Kitamura S, Vaughn DA, Tee JB, Nigam SK (2007) Glial cell-derived neurotrophic factor independent ureteric bud outgrowth from the Wolffian duct. J Am Soc Nephrol 18:3147–3155

    CAS  PubMed  Google Scholar 

  27. Bates CM (2007) Role of fibroblast growth factor receptor signaling in kidney development. Pediatr Nephrol 22:343–349

    PubMed  Google Scholar 

  28. Hains D, Sims-Lucas S, Kish K, Saha M, McHugh K, Bates CM (2008) Role of fibroblast growth factor receptor 2 in kidney mesenchyme. Pediatr Res 64:592–598

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Jain S, Encinas M, Johnson EM Jr, Milbrandt J (2006) Critical and distinct roles for key RET tyrosine docking sites in renal development. Genes Dev 20:321–333

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Costantini F, Shakya R (2006) GDNF/Ret signaling and the development of the kidney. Bioessays 28:117–127

    CAS  PubMed  Google Scholar 

  31. Basson MA, Akbulut S, Watson-Johnson J, Simon R, Carroll TJ, Shakya R, Gross I, Martin GR, Lufkin T, McMahon AP, Wilson PD, Costantini FD, Mason IJ, Licht JD (2005) Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev Cell 8:229–239

    CAS  PubMed  Google Scholar 

  32. Basson MA, Watson-Johnson J, Shakya R, Akbulut S, Hyink D, Constantini FD, Wilson PD, Mason IJ, Licht JD (2006) Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1. Dev Biol 299:466–477

    CAS  PubMed  Google Scholar 

  33. Dunn NR, Winnier GE, Hargett LK, Schrick JJ, Fogo AB, Hogan BL (1997) Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol 188:235–247

    CAS  PubMed  Google Scholar 

  34. Miyazaki Y, Oshima K, Fogo A, Hogan BL, Ichikawa I (2000) Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter. J Clin Invest 105:863–873

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Michos O, Panman L, Vintersten K, Beier K, Zeller R, Zuniga A (2004) Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development 131:3401–3410

    CAS  PubMed  Google Scholar 

  36. Batourina E, Choi C, Paragas N, Bello N, Hensle T, Constantini FD, Schuchardt A, Bacallao RL, Mendelsohn CL (2002) Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Nat Genet 32:109–115

    CAS  PubMed  Google Scholar 

  37. Marose TD, Merkel CE, McMahon AP, Carroll TJ (2008) Beta-catenin is necessary to keep cells of ureteric bud/Wolffian duct epithelium in a precursor state. Dev Biol 314:112–126

    CAS  PubMed  Google Scholar 

  38. Murer L, Benetti E, Artifoni L (2007) Embryology and genetics of primary vesico-ureteric reflux and associated renal dysplasia. Pediatr Nephrol 22:788–797

    PubMed  PubMed Central  Google Scholar 

  39. Batourina E, Tsai S, Lambert S, Sprenkle P, Viana R, Dutta S, Hensle T, Wang F, Niederreither K, McMahon AP, Carroll TJ, Mendelsohn CL (2005) Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder. Nat Genet 37:1082–1089

    CAS  PubMed  Google Scholar 

  40. Brenner-Anantharam A, Cebrian C, Guillaume R, Hurtado R, Sunn TT, Herzlinger D (2007) Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling. Development 134:1967–1975

    CAS  PubMed  Google Scholar 

  41. Viana R, Batourina E, Huang H, Dressler GR, Kobayashi A, Behringer RR, Shapiro E, Hensle T, Lambert S, Mendelsohn C (2007) The development of the bladder trigone, the center of the anti-reflux mechanism. Development 134:3763–3769

    CAS  PubMed  Google Scholar 

  42. Airik R, Bussen M, Singh MK, Petry M, Kispert A (2006) Tbx18 regulates the development of the ureteral mesenchyme. J Clin Invest 116:663–674

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Mahoney ZX, Sammut B, Xavier RJ, Cunningham J, Go G, Brim KL, Stappenbeck TS, Miner JH, Swat W (2006) Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter. Proc Natl Acad Sci USA 103:19872–19877

    CAS  PubMed  Google Scholar 

  44. Iizuka-Kogo A, Ishidao T, Akiyama T, Senda T (2007) Abnormal development of urogenital organs in Dlgh1-deficient mice. Development 134:1799–1807

    CAS  PubMed  Google Scholar 

  45. Murawski IJ, Myburgh DB, Favor J, Gupta IR (2007) Vesico-ureteric reflux and urinary tract development in the Pax2 1Neu+/- mouse. Am J Physiol Renal Physiol 293:F1736–F1745

    CAS  PubMed  Google Scholar 

  46. Murawski IJ, Gupta IR (2006) Vesicoureteric reflux and renal malformations: a developmental problem. Clin Genet 69:105–117

    CAS  PubMed  Google Scholar 

  47. Lu W, Quintero-Rivera F, Fan Y, Alkuraya FS, Donovan DJ, Xi Q, Turbe-Doan A, Li QG, Campbell CG, Shanske AL, Sherr EH, Ahmad A, Peters R, Rilliet B, Parvex P, Bassuk AG, Harris DJ, Ferguson H, Kelly C, Walsh CA, Gronostajski RM, Devriendt K, Higgins A, Ligon AH, Quade BJ, Morton CC, Gusella JF, Maas RL (2007) NFIA haploinsufficiency is associated with a CNS malformation syndrome and urinary tract defects. PLoS Genet 3:e80

    PubMed  PubMed Central  Google Scholar 

  48. Alcaraz A, Vinaixa F, Tejedo-Mateu A, Fores MM, Gotzens V, Mestres CA, Oliveira J, Carretero P (1991) Obstruction and recanalization of the ureter during embryonic development. J Urol 145:410–416

    CAS  PubMed  Google Scholar 

  49. Santicioli P, Maggi CA (1998) Myogenic and neurogenic factors in the control of pyeloureteral motility and ureteral peristalsis. Pharmacol Rev 50:683–721

    CAS  PubMed  Google Scholar 

  50. DiBona GF, Kopp UC (1997) Neural control of renal function. Physiol Rev 77:75–197

    CAS  PubMed  Google Scholar 

  51. Mendelsohn C (2006) Going in circles: conserved mechanisms control radial patterning in the urinary and digestive tracts. J Clin Invest 116:635–637

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Yu J, Carroll TJ, McMahon AP (2002) Sonic hedgehog regulates proliferation and differentiation of mesenchymal cells in the mouse metanephric kidney. Development 129:5301–5312

    CAS  PubMed  Google Scholar 

  53. Caubit X, Lye CM, Martin E, Coré N, Long DA, Vola C, Jenkins D, Garratt AN, Skaer H, Woolf AS, Fasano L (2008) Teashirt 3 is necessary for ureteral smooth muscle differentiation downstream of SHH and BMP4. Development 135:3301–3310

    CAS  PubMed  Google Scholar 

  54. Fujinaka H, Miyazaki Y, Matsusaka T, Yoshida H, Fogo AB, Inagami T, Ichikawa I (2000) Salutary role for angiotensin in partial urinary tract obstruction. Kidney Int 58:2018–2027

    CAS  PubMed  Google Scholar 

  55. Yosypiv IV, El-Dahr SS (2005) Role of the renin-angiotensin system in the development of the ureteric bud and renal collecting system. Pediatr Nephrol 20:1219–1229

    PubMed  Google Scholar 

  56. Oshima K, Miyazaki Y, Brock JW 3rd, Adams MC, Ichikawa I, Pope JC (2001) Angiotensin type II receptor expression and ureteral budding. J Urol 166:1848–1852

    CAS  PubMed  Google Scholar 

  57. Nishimura H, Yerkes E, Hohenfellner K, Miyazaki Y, Ma J, Hunley TE, Yoshida H, Ichiki T, Threadgill D, Phillips JA 3rd, Hogan BM, Fogo A, Brock JW 3rd, Inagami T, Ichikawa I (1999) Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. Mol Cell 3:1–10

    CAS  PubMed  Google Scholar 

  58. Miyazaki Y, Tsuchida S, Nishimura H, Pope JC, Harris RC, McKanna JM, Inagami T, Hogan BL, Fogo A, Ichikawa I (1998) Angiotensin induces the urinary peristaltic machinery during the perinatal period. J Clin Invest 102:1489–1497

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Oliverio MI, Kim HS, Ito M, Le T, Audoly L, Best CF, Hiller S, Kluckman K, Maeda N, Smithies O, Coffman TM (1998) Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Proc Natl Acad Sci USA 95:15496–15501

    CAS  PubMed  Google Scholar 

  60. Esther CR Jr, Howard TE, Marino EM, Goddard JM, Capecchi MR, Bernstein KE (1996) Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest 74:953–965

    CAS  PubMed  Google Scholar 

  61. Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T (1995) Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest 96:2947–2954

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Nagata M, Tanimoto K, Fukamizu A, Kon Y, Sugiyama F, Yagami K, Murakami K, Watanable T (1996) Nephrogenesis and renovascular development in angiotensinogen-deficient mice. Lab Invest 75:745–753

    CAS  PubMed  Google Scholar 

  63. Kong XT, Deng FM, Hu P, Liang FX, Zhou G, Auerbach AB, Genieser N, Nelson PK, Robbins ES, Shapiro E, Kachar B, Sun TT (2004) Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases. J Cell Biol 167:1195–1204

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Hu P, Deng FM, Liang FX, Hu CM, Auerbach AB, Shapiro E, Wu XR, Kachar B, Sun TT (2000) Ablation of uroplakin III gene results in small urothelial plaques, urothelial leakage, and vesicoureteral reflux. J Cell Biol 151:961–972

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Abbott BD, Birnbaum LS, Pratt RM (1987) TCDD-induced hyperplasia of the ureteral epithelium produces hydronephrosis in murine fetuses. Teratology 35:329–334

    CAS  PubMed  Google Scholar 

  66. Okazaki T, Otaka Y, Wang J, Hiai H, Takai T, Ravetch JV, Honjo T (2005) Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b−/−Pdcd1−/− mice. J Exp Med 202:1643–1648

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Lauder AJ, Jolin HE, Smith P, van den Berg JG, Jones A, Wisden W, Smith KG, Dasvarma A, Fallon PG, McKenzie AN (2004) Lymphomagenesis, hydronephrosis, and autoantibodies result from dysregulation of IL-9 and are differentially dependent on Th2 cytokines. J Immunol 173:113–122

    CAS  PubMed  Google Scholar 

  68. Izquierdo L, Porteous M, Paramo PG, Connor JM (1992) Evidence for genetic heterogeneity in hereditary hydronephrosis caused by pelvi-ureteric junction obstruction, with one locus assigned to chromosome 6p. Hum Genet 89:557–560

    CAS  PubMed  Google Scholar 

  69. Mackintosh P, Almarhoos G, Heath DA (1989) HLA linkage with familial vesicoureteral reflux and familial pelvi-ureteric junction obstruction. Tissue Antigens 34:185–189

    CAS  PubMed  Google Scholar 

  70. McDill BW, Li SZ, Kovach PA, Ding L, Chen F (2006) Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation. Proc Natl Acad Sci USA 103:6952–6957

    CAS  PubMed  Google Scholar 

  71. Feliubadalo L, Arbones ML, Manas S, Chillaron J, Visa J, Rodes M, Rousaud F, Zorzano A, Palacin M, Nunes V (2003) Slc7a9-deficient mice develop cystinuria non-I and cystine urolithiasis. Hum Mol Genet 12:2097–2108

    CAS  PubMed  Google Scholar 

  72. Shindo T, Kurihara H, Kuno K, Yokoyama H, Wada T, Kurihara Y, Imai T, Wang Y, Ogata M, Nishimatsu H, Moriyama N, Oh-hashi Y, Morita H, Ishikawa T, Nagai R, Yazaki Y, Matsushima K (2000) ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function. J Clin Invest 105:1345–1352

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS (2001) Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus. J Biol Chem 276:2775–2779

    CAS  PubMed  Google Scholar 

  74. Lloyd DJ, Hall FW, Tarantino LM, Gekakis N (2005) Diabetes insipidus in mice with a mutation in aquaporin-2. PLoS Genet 1:e20

    PubMed  PubMed Central  Google Scholar 

  75. Green M (1951) Further morphological effects of the short ear gene in the house mouse. J Morphol 88:1–22

    CAS  PubMed  Google Scholar 

  76. King JA, Marker PC, Seung KJ, Kinglesy DM (1994) BMP5 and the molecular, skeletal, and soft-tissue alterations in short ear mice. Dev Biol 166:112–122

    CAS  PubMed  Google Scholar 

  77. Kume T, Deng K, Hogan BL (2000) Murine forkhead/winged helix genes Foxc1 (Mf1) and Foxc2 (Mfh1) are required for the early organogenesis of the kidney and urinary tract. Development 127:1387–1395

    CAS  PubMed  Google Scholar 

  78. Zhou Y, Lim KC, Onodera K, Takahashi S, Ohta J, Minegishi N, Tsai FY, Orkin SH, Yamamoto M, Engel JD (1998) Rescue of the embryonic lethal hematopoietic defect reveals a critical role for GATA-2 in urogenital development. EMBO J 17:6689–6700

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Warot X, Fromental-Ramain C, Fraulob V, Chambon P, Dolle P (1997) Gene dosage-dependent effects of the Hoxa-13 and Hoxd-13 mutations on morphogenesis of the terminal parts of the digestive and urogenital tracts. Development 124:4781–4791

    CAS  PubMed  Google Scholar 

  80. Held T, Paprotta I, Khulan J, Hemmerlein B, Binder L, Wolf S, Schubert S, Meinhardt A, Engel W, Adham IM (2006) Hspa4l-deficient mice display increased incidence of male infertility and hydronephrosis development. Mol Cell Biol 26:8099–8108

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Aoki Y, Mori S, Kitajima K, Yokoyama O, Kanamaru H, Okada K, Yokota Y (2004) Id2 haploinsufficiency in mice leads to congenital hydronephrosis resembling that in humans. Genes Cells 9:1287–1296

    CAS  PubMed  Google Scholar 

  82. Debiec H, Kutsche M, Schachner M, Ronco M (2002) Abnormal renal phenotype in L1 knockout mice: a novel cause of CAKUT. Nephrol Dial Transplant 17 [Suppl 9]:42–44

    CAS  PubMed  Google Scholar 

  83. Gamp AC, Tanaka Y, Lullmann-Rauch R, Wittke D, D’Hooge R, De Deyn PP, Moser T, Maier H, Hartmann D, Reiss K, Illert AL, von Figura K, Saftig P (2003) LIMP-2/LGP85 deficiency causes ureteric pelvic junction obstruction, deafness and peripheral neuropathy in mice. Hum Mol Genet 12:631–646

    CAS  PubMed  Google Scholar 

  84. Carter T (1953) The genetics of luxate mice III. Horseshoe kidney, hydronephrosis and lumbar reduction. J Genet 51:441–457

    Google Scholar 

  85. Singh S, Robinson M, Nahi F, Coley B, Robinson ML, Bates CM, Kornacker K, McHugh KM (2007) Identification of a unique transgenic mouse line that develops megabladder, obstructive uropathy, and renal dysfunction. J Am Soc Nephrol 18:461–471

    CAS  PubMed  Google Scholar 

  86. Takahashi N, Chernavvsky DR, Gomez RA, Igarashi P, Gitelman HJ, Smithies O (2000) Uncompensated polyuria in a mouse model of Bartter’s syndrome. Proc Natl Acad Sci USA 97:5434–5439

    CAS  PubMed  Google Scholar 

  87. Takahashi N, Lopez ML, Cowhig JE Jr, Taylor MA, Hatada T, Riggs E, Lee G, Gomez RA, Kim HS, Smithies O (2005) Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type. J Am Soc Nephrol 16:125–132

    PubMed  Google Scholar 

  88. Vega QC, Worby CA, Lechner MS, Dixon JE, Dressler GR (1996) Glial cell line-derived neurotrophic factor activates the receptor tyrosine kinase RET and promotes kidney morphogenesis. Proc Natl Acad Sci USA 93:10657–10661

    CAS  PubMed  Google Scholar 

  89. Sainio K, Suvanto P, Davies J, Wartiovaara J, Wartiovaara K, Saarma M, Arumäe U, Meng X, Lindahl M, Pachnis V, Sariola H (1997) Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development 124:4077–4087

    CAS  PubMed  Google Scholar 

  90. Yu OH, Murawski IJ, Myburgh DB, Gupta IR (2004) Overexpression of RET leads to vesicoureteric reflux in mice. Am J Physiol Renal Physiol 287:F1123–F1130

    CAS  PubMed  Google Scholar 

  91. Lu W, van Eerde AM, Fan X, Quintero-Rivera F, Kulkarni S, Ferguson H, Kim HG, Fan Y, Xi Q, Li QG, Sanlaville D, Andrews W, Sundaresan V, Bi W, Yan J, Giltay JC, Wijmenga C, de Jong TP, Feather SA, Woolf AS, Rao Y, Lupski JR, Eccles MR, Quade BJ, Gusella JF, Morton CC, Maas RL (2007) Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. Am J Hum Genet 80:616–632

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Bertoli-Avella AM, Conte ML, Punzo F, de Graaf BM, Lama G, La Manna A, Polito C, Grassia C, Nobili B, Rambaldi PF, Oostra BA, Perrotta S (2008) ROBO2 gene variants are associated with familial vesicoureteral reflux. J Am Soc Nephrol 19:825–831

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Lorenz JN, Baird NR, Judd LM, Noonan WT, Andringa A, Doetschman T, Manning PA, Liu LH, Miller ML, Schull GE (2002) Impaired renal NaCl absorption in mice lacking the ROMK potassium channel, a model for type II Bartter’s syndrome. J Biol Chem 277:37871–37880

    CAS  PubMed  Google Scholar 

  94. Oxburgh L, Chu GC, Michael SK, Robertson EJ (2004) TGFbeta superfamily signals are required for morphogenesis of the kidney mesenchyme progenitor population. Development 131:4593–4605

    CAS  PubMed  Google Scholar 

  95. Chi L, Zhang S, Lin Y, Prunskaite-Hyyrylainen R, Vuolteenaho R, Itaranta P, Vainio S (2004) Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelial Wnt11, mesenchymal Gdnf and stromal Fgf7 signalling during kidney development. Development 131:3345–3356

    CAS  PubMed  Google Scholar 

  96. Lo SH, Yu QC, Degenstein L, Chen LB, Fuchs E (1997) Progressive kidney degeneration in mice lacking tensin. J Cell Biol 136:1349–1361

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgment

The author wishes to thank Drs. Helen Liapis and Matthew Coussens for their critical reading of the manuscript. F.C. has been supported in part by a National Institutes of Health (NIH) grant (DK067386) and the George M. O’Brien Washington University Center for Kidney Disease Research (NIHP30DK079333).

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Correspondence to Feng Chen.

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Chen, F. Genetic and developmental basis for urinary tract obstruction. Pediatr Nephrol 24, 1621–1632 (2009). https://doi.org/10.1007/s00467-008-1072-y

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