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Embryology

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Pediatric Nephrology

Abstract

In the last few decades, considerable advances have been made in understanding kidney development (1, 2). In previous years, this process was described in purely anatomic terms, but we can now interpret the anatomy in terms of dynamic morphogenesis, or acquisition of form, driven by the expression of specific genes. Although our long-term aim is to understand human kidney development, most functional studies have been performed in mice and therefore these animal experiments are described in some detail.

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References

  1. Woolf AS, Jenkins D. Development of the kidney. In Heptinstall’s Pathology of the Kidney, 6th edn. Jennette JC, Olson JL, Schwartz MM, Silva FG (eds.). Philadelphia-New York, USA, Lippincott-Raven, 2006, pp. 71–95.

    Google Scholar 

  2. Woolf AS, Welham SJM, Hermann MM, Winyard PJD. Maldevelopment of the human kidney and lower urinary tract: an overview. In The Kidney: From Normal Development to Congenital Disease. Vize PD, Woolf AS, Bard JBL (eds.). Elsevier Science/Academic, Amsterdam, 2003, pp. 377–393.

    Google Scholar 

  3. Kerecuk L, Schreuder MF, Woolf AS. Human renal tract malformations: perspectives for Nephrologists. Nat Clin Pract Nephrol 2008;4:312–325.

    Article  PubMed  Google Scholar 

  4. Woolf AS, Hillman KA. Unilateral renal agenesis and the congenital solitary functioning kidney: developmental, genetic and clinical perspectives. BJU Int 2007;99:17–21.

    Article  PubMed  CAS  Google Scholar 

  5. Woolf AS, Price K, Scambler PJ, Winyard PJD. Evolving concepts in human renal dysplasia. J Am Soc Nephrol 2004;15:998–1007.

    Article  PubMed  Google Scholar 

  6. Potter EL. Normal and abnormal development of the kidney. Chicago, Year Book Medical, 1972.

    Google Scholar 

  7. Keller G, Zimmer G, Mall G, Ritz E, Amann K. Nephron number in patients with primary hypertension. N Engl J Med 2003;348:101–108.

    Article  PubMed  Google Scholar 

  8. Welham SJM, Wade A, Woolf AS. Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis. Kidney Int 2002;61:1231–1242.

    Article  PubMed  CAS  Google Scholar 

  9. Woolf AS, Yuan HT. The development of kidney blood vessels. In The Kidney: From Normal Development to Congenital Disease. Vize PD, Woolf AS, Bard JBL (eds.). Elsevier Science/Academic, Amsterdam, 2003, pp. 251–266.

    Google Scholar 

  10. Sariola H, Timpl R, von der Mark K et al. Dual origin of glomerular basement membrane. Dev Biol 1984;101:86–96.

    Article  PubMed  CAS  Google Scholar 

  11. Jenkins D, Winyard PJD, Woolf AS. Immunohistochemical analysis of sonic hedgehog signalling in normal human urinary tract development. J Anat 2007;211:620–629.

    Article  PubMed  CAS  Google Scholar 

  12. Dekel B, Amariglio N, Kaminski N, Schwartz A, Goshen E, Arditti FD, Tsarfaty I, Passwell JH, Reisner Y, Rechavi G. Engranftment and differentiation of human metanephroi into functional mature nephrons after transplantation into mice is accompanied by a profile of gene expression similar to normal kidney development. J Am Soc Nephol 2002;13:977–990.

    CAS  Google Scholar 

  13. Price KL, Long DA, Jina N, Liapis H, Hubank M, Woolf AS, Winyard PJ. Microarray interrogation of human metanephric mesenchymal cells highlights potentially important molecules in vivo. Physiol Genomics 2007;23:193–202.

    Google Scholar 

  14. Grobstein C. Mechanisms of organotypic tissue interactions. Natl Cancer Inst Mono 1967;26:279–299.

    CAS  Google Scholar 

  15. Sariola H, Saarma M, Sainio K et al. Dependence of kidney morphogenesis on the expression of nerve growth factor receptor. Science 1991;254:571–573.

    Article  PubMed  CAS  Google Scholar 

  16. Woolf AS, Kolatsi-Joannou M, Hardman P et al. Roles of hepatocyte growth factor/scatter factor and the MET receptor in the early development of the metanephros. J Cell Biol 1995;128:171–184.

    Article  PubMed  CAS  Google Scholar 

  17. Klein G, Langegger M, Timpl R et al. Role of laminin A chain in the development of epithelial cell polarity. Cell 1988;55:331–341.

    Article  PubMed  CAS  Google Scholar 

  18. Woolf AS, Bosch RJ, Fine LG. Gene transfer into the mammalian kidney: micro-transplantation of retrovirus-transduced metanephric tissue. Exp Nephrol 1993;1:41–48.

    PubMed  CAS  Google Scholar 

  19. Qiao J, Herzlinger D. The metanephric blastema differentiates into collecting system and nephron epithelia in vitro. Development 1995;121:3207–3214.

    PubMed  CAS  Google Scholar 

  20. Burrow C, Wilson PD. A putative Wilms tumor-secreted growth factor activity required for primary culture of human nephroblasts. Proc Natl Acad Sci USA 1993;90:6066–6070.

    Article  PubMed  CAS  Google Scholar 

  21. Boyden EA. Experimental obstruction of the mesonephric ducts. Proc Soc Exp Biol Med 1927;24:572–576.

    Google Scholar 

  22. Yang SP, Woolf AS, Quinn F, Winyard PJD. Deregulation of renal transforming growth factor-β1 after experimental short-term ureteric obstruction in fetal sheep. Am J Pathol 2001;159:109–117.

    Article  PubMed  CAS  Google Scholar 

  23. Tse HK, Leung MB, Woolf AS, Menke AL, Hastie ND, Gosling JA, Pang CP, Shum AS. Implication of Wt1 in the pathogenesis of nephrogenic failure in a mouse model of retinoic acid-induced caudal regression syndrome. Am J Pathol 2005;166:1295–1307.

    Article  PubMed  CAS  Google Scholar 

  24. Kanwar YS, Nayak B, Lin S, Akagi S, Xie P, Wada J, Chugh SS, Danesh FR. Hyperglycemia: its imminent effects on mammalian nephrogenesis. Pediatr Nephrol 2005;20:858–866.

    Article  PubMed  Google Scholar 

  25. Welham SJ, Riley PR, Wade A, Hubank M, Woolf AS. Maternal diet programs embryonic kidney gene expression. Physiol Genomics 2005;22:48–56.

    Article  PubMed  CAS  Google Scholar 

  26. Dressler GR, Wilkinson JE, Rothenpieler UW et al. Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities. Nature 1993;362:65–67.

    Article  PubMed  CAS  Google Scholar 

  27. Torres M, Gomez-Pardo E, Dressler GR et al. Pax-2 controls multiple steps of urogenital development. Development 1995;121:4057–4065.

    PubMed  CAS  Google Scholar 

  28. The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) http://www.gudmap.org/

  29. Mendelsohn C, Lohnes D, Decimo S et al. Function of the retinoic acid receptors (RAR) during development. Development 1994;120:2749–2771.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  31. Winyard PJD, Risdon RA, Sams VR et al. The PAX2 transcription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations. J Clin Invest 1996;98:451–459.

    Article  PubMed  CAS  Google Scholar 

  32. Oliver JA, Maarouf O, Cheema FH, Martens TP, Al-Awqati Q. The renal papilla is a niche for adult kidney stem cells. J Clin Invest 2004;114:795–804.

    PubMed  CAS  Google Scholar 

  33. Kampmeier OF. The metanephros or so-called permanent kidney in part provisional and vestigial. Anat Rec 1926;33:115–120.

    Article  Google Scholar 

  34. Kim J, Lee GS, Tisher CC, Madsen KM. Role of apoptosis in development of the ascending thin limb of the loop of Henle in rat kidney. Am J Physiol 1996;271:F831–F845.

    PubMed  CAS  Google Scholar 

  35. Kim J, Cha JH, Tisher CC, Madsen KM. Role of apoptotic and nonapoptotic death in removal of intercalated cells from developing rat kidney. Am J Physiol 1996;270:F575–F592.

    PubMed  CAS  Google Scholar 

  36. Fierlbeck W, Liu A, Coyle R, Ballermann BJ. Endothelial cell apoptosis during glomerular capillary lumen formation in vivo. J Am Soc Nephrol 2003;14:1349–1354.

    Article  PubMed  CAS  Google Scholar 

  37. Nadasy T, Laszik Z, Lajoie G, Blick KE, Wheeler DE, Silva FG. Proliferative activity of cyst epithelium in human renal cystic diseases. J Am Soc Nephrol 1995;5:1462–1468.

    Google Scholar 

  38. Veis DJ, Sorenson CM, Shutter JR et al. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys and hypopigmented hair. Cell 1994;75:229–240.

    Article  Google Scholar 

  39. Winyard PJD, Nauta J, Lirenman DS et al. Deregulation of cell survival in cystic and dysplastic renal development. Kidney Int 1996;49:135–146.

    Article  PubMed  CAS  Google Scholar 

  40. Herzlinger D, Koseki C, Mikawa T et al. Metanephric mesenchyme contains multipotent stem cells whose fate is restricted after induction. Development 1992;114:565–572.

    PubMed  CAS  Google Scholar 

  41. Schedl A. Renal abnormalities and their developmental origin. Nat Rev Genet 2007;8:791–802.

    Article  PubMed  CAS  Google Scholar 

  42. Yu J, McMahon AP, Valerius MT. Recent genetic studies of mouse kidney development. Curr Opin Genet Dev 2004;14:550–557.

    Article  PubMed  CAS  Google Scholar 

  43. Valerius MT, Patterson LT, Feng Y, Potter SS. Hoxa11 is upstream of integrin α8 expression in the developing kidney. Proc Natl Acad Sci USA 2002;99:8090–8095.

    Article  PubMed  CAS  Google Scholar 

  44. Gong KQ, Yallowitz AR, Sun H, Dressler GR, Wellik DM. A Hox-Eya-Pax complex regulates early kidney developmental gene expression. Mol Cell Biol 2007;27:7661–7668.

    Article  PubMed  CAS  Google Scholar 

  45. Yang SP, Woolf AS, Yuan HT, Scott RJ, Risdon RA, O’Hare MJ, Winyard PJD. Potential biological role of transforming growth factor β1 in human congenital kidney malformations. Am J Pathol 2000; 157:1633–1647.

    Article  PubMed  CAS  Google Scholar 

  46. Cale CM, Winyard PJD, Klein NJ, Woolf AS. Inflammatory mediators in human renal dysplasia. Nephrol Dial Transplant 2000;15:173–183.

    Article  PubMed  CAS  Google Scholar 

  47. Mikazaki Y, Ichikawa I. Role of the angiotensin receptor in the development of the mammalian kidney and urinary tract. Comp Biochem Physiol A Mol Integr Physiol 2001;128:89–97.

    Article  Google Scholar 

  48. Kobayashi A, Kwan KM, Carroll TJ, McMahon AP, Mendelsohn CL, Behringer RR. Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development 2005;132:2809–2823.

    Article  PubMed  CAS  Google Scholar 

  49. Sajithlal G, Zou D, Silvius D, Xu PX. Eyal acts as a critical regulator for specifying the metanephric mesenchyme. Dev Biol 2005;284:323–336.

    Article  PubMed  CAS  Google Scholar 

  50. Okada M, Fujimaru R, Morimoto N, Satomura K, Kaku Y, Tsuzuki K, Nozu K, Okuyama T, Iijima K. EYA1 and SIX1 gene mutations in Japanese patients with branchio-oto-renal (BOR) syndrome and related conditions. Pediatr Nephrol 2006;21:475–481.

    Article  PubMed  Google Scholar 

  51. Xu PX, Zheng W, Huang L, Maire P, Laclef C, Silvius D. Six1 is required for the early organogenesis of mammalian kidney. Development 2003;130:3085–3095.

    Article  PubMed  CAS  Google Scholar 

  52. Koseki C, Herzlinger D, Al-Awqati Q. Apoptosis in metanephric development. J Cell Biol 1992;119:1322–1333.

    Article  Google Scholar 

  53. Perantoni AO, Dove LF, Karavanova I. Basic fibroblast growth factor can mediate the early inductive events in renal development. Proc Natl Acad Sci USA 1995;92:4696–4700.

    Article  PubMed  CAS  Google Scholar 

  54. Barasch J, Pressler L, Connor J et al. A ureteric bud cell line induces nephrogenesis in two steps by two distinct signals. Am J Physiol 1996;271:F50–F61.

    PubMed  CAS  Google Scholar 

  55. Barasch J, Yang J, Qiao J, Tempst P, Erdjument-Bromage H, Leung W, Oliver JA. Tissue inhibitor of metalloproteinase-2 stimulates mesenchymal growth and regulates epithelial branching during morphogenesis of the rat metanephros. J Clin Invest 1999;103:1299–1307.

    Article  PubMed  CAS  Google Scholar 

  56. Self M, Lagutin OV, Bowling B, Hendrix J, Cai Y, Dressler GR, Oliver G. Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J 2006;25:5214–5228.

    Article  PubMed  CAS  Google Scholar 

  57. Weber S, Taylor JC, Winyard P, Baker KF, Sullivan-Brown J, Schild R, Knüppel T, Zurowska AM, Caldas-Alfonso A, Litwin M, Emre S, Ghiggeri GM, Bakkaloglu A, Mehls O, Antignac C, Network E, Schaefer F, Burdine RD. SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol 2008;19:891–903.

    Article  PubMed  CAS  Google Scholar 

  58. Larsson SH, Charlieu J-P, Miyagawa K et al. Subnuclear localization of WT1 in splicing of transcription factor domains is regulated by alternative splicing. Cell 1995;81:391–401.

    Article  PubMed  CAS  Google Scholar 

  59. Kreidberg JA, Sariola H, Loring JM et al. WT-1 is required for early kidney development. Cell 1993;74:679–691.

    Article  PubMed  CAS  Google Scholar 

  60. Ruteshouser EC, Robinson SM, Huff V. Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors. Genes Chromosomes Cancer 2008;47:461–470.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  62. 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. Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development 2001;3105–3115.

    Google Scholar 

  63. Reardon W, Casserly LF, Birkenhäger R, Kohlhase J. Kidney failure in Townes-Brocks syndrome: an under recognized phenomenon? Am J Med Genet A 2007;143A:2588–2591.

    Article  PubMed  CAS  Google Scholar 

  64. Clark P, Dziarmaga A, Eccles M, Goodyer P. Rescue of defective branching nephrogenesis in renal-coloboma syndrome by the caspase inhibitor, Z-VAD-fmk. J Am Soc Nephrol 2004;15:299–305.

    Article  PubMed  CAS  Google Scholar 

  65. Rothenpieler UW, Dressler GR. Pax-2 is required for mesenchyme-to-epithelium conversion during kidney development. Development 1993;119:711–720.

    PubMed  CAS  Google Scholar 

  66. Favor J, Sandulache R, Neuhauser-Klaus A et al. The mouse Pax2 1Neu mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye and kidney. Proc Natl Acad Sci USA 1996;93:13870–13875.

    Article  PubMed  CAS  Google Scholar 

  67. Sanyanusin P, Schimmentl LA, McNoe LA et al. Mutations of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Nature Genet 1995;9:358–364.

    Article  PubMed  CAS  Google Scholar 

  68. Kolatsi-Joannou M, Moore R, Winyard PJD et al. Expression of hepatocyte growth factor/scatter factor and its receptor, MET, suggests roles in human embryonic organogenesis. Pediatr Res 1997;41:657–665.

    Article  PubMed  CAS  Google Scholar 

  69. Karp SL, Ortiz-Arduan A, Li S et al. Epithelial differentiation of metanephric mesenchymal cells after stimulation with hepatocyte growth factor or embryonic spinal cord. Proc Natl Acad Sci USA 1994;91:5286–5290.

    Article  PubMed  CAS  Google Scholar 

  70. Muller U, Wang D, Denda S et al. Integrin α8β1 is critically important for epithelial-mesenchymal interactions during kidney development. Cell 1997;88:603–613.

    Article  PubMed  CAS  Google Scholar 

  71. Denda S, Reichardt LF, Müller U. Identification of osteopontin as a novel ligand for the integrin α8β1 and potential roles for this integrin-ligand interaction in kidney morphogenesis. Mol Biol Cell 1998;9:1425–1435.

    PubMed  CAS  Google Scholar 

  72. Sorenson CM, Rogers SA, Korsmeyer SJ et al. Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am J Physiol 1995;268:F73–F81.

    PubMed  CAS  Google Scholar 

  73. Klein G, Langegger M, Garidis C et al. Neural cell adhesion molecules during embryonic induction and development of the kidney. Development 1988;102:749–761.

    PubMed  CAS  Google Scholar 

  74. Gumbiner B, Stevenson B, Grimalfi A. The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol 1988;107:1575–1587.

    Article  PubMed  CAS  Google Scholar 

  75. McNeil H, Ozawa M, Kemler R et al. Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity. Cell 1990;62:309–316.

    Article  Google Scholar 

  76. Ekblom P. Formation of basement membrane in the embryonic kidney: an immunohistological study. J Cell Biol 1981;91:1–10.

    Article  PubMed  CAS  Google Scholar 

  77. Sorokin L, Sonnenberg A, Aumailley M et al. Recognition of the laminin E8 cell-binding site by an integrin possessing the α6 subunit is essential for epithelial polarization in developing kidney tubules. J Cell Biol 1990;111:1265–1273.

    Article  PubMed  CAS  Google Scholar 

  78. Torban E, Dziarmaga A, Iglesias D, Chu LL, Vassilieva T, Little M, Eccles M, Discenza M, Pelletier J, Goodyer P. PAX2 activates WNT4 expression during mammalian kidney development. J Biol Chem 2006;281:12705–12712.

    Article  PubMed  CAS  Google Scholar 

  79. Stark K, Vainio S, Vassileva G et al. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 1994;372:679–683.

    Article  PubMed  CAS  Google Scholar 

  80. Mandel H, Shemer R, Borochowitz ZU, Okopnik M, Knopf C, Indelman M, Drugan A, Tiosano D, Gershoni-Baruch R, Choder M, Sprecher E. SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet 2008;82:39–47.

    Article  PubMed  CAS  Google Scholar 

  81. Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ. A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman. N Engl J Med 2004;351:792–798.

    Article  PubMed  CAS  Google Scholar 

  82. Dudley AT, Lyons KM, Robertson EJ. A requirement for BMP-7 during development of the mammalian kidney and eye. Genes Dev 1995;9:2795–2807.

    Article  PubMed  CAS  Google Scholar 

  83. Luo G, Hofmann C, Bronckers ALJJ et al. BMP-7 is an inducer of nephrogenesis and is also required for eye development and skeletal patterning. Genes Dev 1995;9:2808–2820.

    Article  PubMed  CAS  Google Scholar 

  84. Barasch J, Yang J, Ware CB, Taga T, Yoshida K, Erdjument-Bromage H, Tempst P, Parravicini E, Malach S, Aranoff T, Oliver JA. Mesenchymal to epithelial conversion in rat metanephros is induced by LIF. Cell 1999;99:377–386.

    Article  PubMed  CAS  Google Scholar 

  85. Levashova ZB, Plisov SY, Perantoni AO. Conditionally immortalized cell line of inducible metanephric mesenchyme. Kidney Int 2003; 63:2075–2087.

    Article  PubMed  CAS  Google Scholar 

  86. Rogers SA, Ryan G, Hammerman MR. Insulin-like growth factors I and II are produced in the metanephros and are required for growth and development in vitro. J Cell Biol 1991;113:1447–1453.

    Article  PubMed  CAS  Google Scholar 

  87. Jung AC, Denholm B, Skaer H, Affolter M. Renal tubule development in Drosophila: a closer look at the cellular level. J Am Soc Nephrol 2005;16:322–338.

    Article  PubMed  CAS  Google Scholar 

  88. Wingert RA, Selleck R, Yu J, Song HD, Chen Z, Song A, Zhou Y, Thisse B, Thisse C, McMahon AP, Davidson AJ. The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros. PLoS Genet 2007;3:1922–1938.

    Article  PubMed  CAS  Google Scholar 

  89. Vilar J, Gilbert T, Moreau E, Merlet-Bénichou C. Metanephros organogenesis is highly stimulated by vitamin A derivatives in organ culture. Kidney Int 1996;49:1478–1487.

    Article  PubMed  CAS  Google Scholar 

  90. Vilar J, Lalou C, Duong VH, Charrin S, Hardouin S, Raulais D, Merlet-Bénichou C, Leliévre-Pégorier M. Midkine is involved in kidney development and in its regulation by retinoids. J Am Soc Nephrol 2002;13:668–676.

    PubMed  CAS  Google Scholar 

  91. Cheng HT, Kim M, Valerius MT, Suerdran K, Schuster-Gossler K, Gossler A, McMahon AP, Kopan R. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development 2007;134:801–811.

    Article  PubMed  CAS  Google Scholar 

  92. Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC. Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet 2005;37:964–968.

    Article  PubMed  CAS  Google Scholar 

  93. Pryde PG, Sedman AB, Nugent CE, Barr M Jr. Angiotensin-converting enzyme inhibitor fetopathy. J Am Soc Nephrol 1993;3:1575–1582.

    PubMed  CAS  Google Scholar 

  94. Nakai S, Sugitani Y, Sato H, Ito S, Miura Y, Ogawa M, Nishi M, Jishage K, Minowa O, Noda T. Crucial roles of Brn1 in distal tubule formation and function in mouse kidney. Development 2003;130:4751–4759.

    Article  PubMed  CAS  Google Scholar 

  95. Ryan G, Steele-Perkins V, Morris JF et al. Repression of Pax-2 by WT1 during normal kidney development. Development 1995;121:867–875.

    PubMed  CAS  Google Scholar 

  96. Yang Y, Jeanpierre C, Dressler GR, Lacoste M, Niaudet P, Gubler MC. WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis. Am J Pathol 1999;154:181–192.

    Article  PubMed  CAS  Google Scholar 

  97. Gwin K, Cajaiba MM, Caminoa-Lizarralde A, Picazo ML, Nistal M, Reyes-Múgica M. Expanding the clinical spectrum of Frasier syndrome. Pediatr Dev Pathol 2008;11:122–127.

    Article  PubMed  Google Scholar 

  98. Dreyer SD, Zhou G, Baldini A, Winterpacht A, Zabel B, Cole W, Johnson RL, Lee B. Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nat Genet 1998;19:47–50.

    Article  PubMed  CAS  Google Scholar 

  99. Miner JH. Developmental biology of glomerular basement membrane components. Curr Opin Nephrol Hypertens 1998;7:13–19.

    Article  PubMed  CAS  Google Scholar 

  100. Morello R, Zhou G, Dreyer SD, Harvey SJ, Ninomiya Y, Thorner PS, Miner JH, Cole W, Winterpacht A, Zabel B, Oberg KC, Lee B. Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. Nat Genet 2001;27:205–208.

    Article  PubMed  CAS  Google Scholar 

  101. Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K. Positionally cloned gene for a novel glomerular protein—nephrin—is mutated in congenital nephrotic syndrome. Mol Cell 1998;1:575–82.

    Article  PubMed  Google Scholar 

  102. Philippe A, Nevo F, Esquivel EL, Reklaityte D, Gribouval O, Tête MJ, Loirat C, Dantal J, Fischbach M, Pouteil-Noble C, Decramer S, Hoehne M, Benzing T, Charbit M, Niaudet P, Antignac C. Nephrin mutations can cause childhood-onset steroid-resistant nephrotic syndrome. J Am Soc Nephrol 2008;19:1871–1878.

    Google Scholar 

  103. Roselli S, Gribouval O, Boute N, Sich M, Benessy F, Attié T, Gubler MC, Antignac C. Podocin localizes in the kidney to the slit diaphragm area. Am J Pathol 2002;160:131–139.

    Article  PubMed  CAS  Google Scholar 

  104. Philippe A, Weber S, Esquivel EL, Houbron C, Hamard G, Ratelade J, Kriz W, Schaefer F, Gubler MC, Antignac C. A missense mutation in podocin leads to early and severe renal disease in mice. Kidney Int 2008;73:1038–1047.

    Article  PubMed  CAS  Google Scholar 

  105. Jarad G, Cunningham J, Shaw AS, Miner JH. Proteinuria precedes podocyte abnormalities in Lamb2-/- mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Invest 2006;116:2272–2279.

    Article  PubMed  CAS  Google Scholar 

  106. Zenker M, Aigner T, Wendler O, Tralau T, Müntefering H, Fenski R, Pitz S, Schumacher V, Royer-Pokora B, Wühl E, Cochat P, Bouvier R, Kraus C, Mark K, Madlon H, Dötsch J, Rascher W, Maruniak-Chudek I, Lennert T, Neumann LM, Reis A. Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. Hum Mol Genet 2004;13:2625–2632.

    Article  PubMed  CAS  Google Scholar 

  107. Abrahamson DR, St John PL, Isom K, Robert B, Miner JH. Partial rescue of glomerular laminin α5 mutations by wild-type endothelia produce hybrid glomeruli. J Am Soc Nephrol 2007;18:2285–2293.

    Article  PubMed  Google Scholar 

  108. Miner JH, Li C. Defective glomerulogenesis in the absence of laminin alpha5 demonstrates a developmental role for the kidney glomerular basement membrane. Dev Biol 2000;217:278–289.

    Article  PubMed  CAS  Google Scholar 

  109. Pozzi A, Jarad G, Moeckel GW, Coffa S, Zhang X, Gewin L, Eremina V, Hudson BG, Borza DB, Harris RC, Holzman LB, Phillips CL, Fassler R, Quaggin SE, Miner JH, Zent R. β1 integrin expression by podocytes is required to maintain glomerular structural integrity. Dev Biol 2008;316:288–301.

    Article  PubMed  CAS  Google Scholar 

  110. Kreidberg JA, Donovan MJ, Goldstein SL, Rennke H, Shepherd K, Jones RC, Jaenisch R. α3β1 integrin has a crucial role in kidney and lung organogenesis. Development 1996;122:3537–3547.

    PubMed  CAS  Google Scholar 

  111. Bernstein J, Cheng F, Roska J. Glomerular differentiation in metanephric culture. Lab Invest 1981;45:183–190.

    PubMed  CAS  Google Scholar 

  112. Sariola H, Ekblom P, Lehtonen E, et al. Differentiation and vascularisation of the metanephric kidney grafted on the chorioallantoic membrane. Dev Biol 1983;96:427–435.

    Article  PubMed  CAS  Google Scholar 

  113. Loughna S, Hardman P, Landels E et al. A molecular and genetic analysis of renal glomerular capillary development. Angiogenesis 1997;1:84–101.

    Article  PubMed  CAS  Google Scholar 

  114. Oliver JA, Barasch J, Yang J, Herzlinger D, Al-Awqati Q. Metanephric mesenchyme contains embryonic renal stem cells. Am J Physiol Renal Physiol 2002;283:F799–F809.

    PubMed  Google Scholar 

  115. Robert B, St John PL, Abrahamson DR. Direct visualization of renal vascular morphogenesis in Flk1 heterozygous mutant mice. Am J Physiol 1998;275:F164–F172.

    PubMed  CAS  Google Scholar 

  116. Hyink DP, Tucker DC, St. John PL et al. Endogenous origin of glomerular endothelial and mesangial cells in grafts of embryonic kidneys. Am J Physiol 1996;270:F886–F899.

    PubMed  CAS  Google Scholar 

  117. Tufro A, Norwood VF, Carey RM, Gomez RA. Vascular endothelial growth factor induced nephrogenesis and vasculogenesis. J Am Soc Nephrol 1999:2125–2134.

    Google Scholar 

  118. Kolatsi-Joannou M, Yuan HT, Li X, Suda T, Woolf AS. Expression and potential role of angiopoietins and Tie-2 in early development of the mouse metanephros. Dev Dyn 2001;222:120–126.

    Article  PubMed  CAS  Google Scholar 

  119. Loughna S, Yuan HT, Woolf AS. Effects of oxygen on vascular patterning in Tie1/LacZ metanephric kidneys in vitro. Biochem Biophys Res Commun 1998;247:361–366.

    Article  PubMed  CAS  Google Scholar 

  120. Freeburg PB, Robert B, St John PL, Abrahamson DR. Podocyte expression of hypoxia-inducible factor (HIF)-1 and HIF-2 during glomerular development. J Am Soc Nephrol 2003;14:927–938.

    Article  PubMed  CAS  Google Scholar 

  121. Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, Gerber HP, Kikkawa Y, Miner JH, Quaggin SE. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest 2003;111:707–716.

    PubMed  CAS  Google Scholar 

  122. Takahashi T, Takahashi K, Gerety S, Wang H, Anderson DJ, Daniel TO. Temporally compartmentalized expression of ephrin-B2 during renal glomerular development, J Am Soc Nephrol 2001;12:2673–2682.

    PubMed  CAS  Google Scholar 

  123. Sequeira Lopez ML, Pentz ES, Robert B, Abrahamson DR, Gomez RA. Embryonic origins and lineage of juxtaglomerular cells. Am J Physiol Renal Physiol 2001;281:F345–F356.

    PubMed  CAS  Google Scholar 

  124. Sequeira López ML, Pentz ES, Nomasa T, Smithies O, Gomez RA. Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened. Dev Cell 2004;6:719–728.

    Article  PubMed  Google Scholar 

  125. Bensoussan M, Heudes D, Nahmias C et al. Organ culture of rat kidney: a model for angiotensin II receptor ontogenic studies. Kidney Int 1995;48:1635–1640.

    Article  PubMed  CAS  Google Scholar 

  126. Fogo A, Yoshida Y, Yared A et al. Importance of angiogenic action of angiotensin II in the glomerular growth of maturing kidneys. Kidney Int 1990;38:1068–1074.

    Article  PubMed  CAS  Google Scholar 

  127. Pitera JE, Woolf AS, Gale NW, Yancopoulos GD, Yuan HT. Dysmorphogenesis of kidney cortical peritubular capillaries in angiopoietin-2-deficient mice. Am J Pathol 2004;165:1895–1906.

    Article  PubMed  CAS  Google Scholar 

  128. Davis B, Dei Cas A, Long DA, White KE, Hayward A, Ku CH, Woolf AS, Bilous R, Viberti G, Gnudi L. Podocyte-specific expression of angiopoietin-2 causes proteinuria and apoptosis of glomerular endothelia. J Am Soc Nephrol 2007;18:2320–2399.

    Article  PubMed  CAS  Google Scholar 

  129. Leveen P, Pekny M, Gebre Medhin S et al. Mice deficient for PDGFB show renal, cardiovascular, and hematological abnormalities. Genes Dev 1994;8:1875–1887.

    Article  PubMed  CAS  Google Scholar 

  130. Soriano P. Abnormal kidney development and hematological disorders in PDGFB receptor mutant mice. Genes Dev 1994;8:1888–1896.

    Article  PubMed  CAS  Google Scholar 

  131. Kolatsi-Joannou M, Woolf AS, Hardman P et al. The hepatocyte growth factor/scatter factor (HGF/SF) receptor, MET, transduces a morphogenetic signal in renal glomerular fibromuscular mesangial cells. J Cell Sci 1995;108:3703–3714.

    PubMed  CAS  Google Scholar 

  132. Jing S, Wun D, Yu Y et al. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-α a novel receptor for GDNF. Cell 1996;85:1113–1124.

    Article  PubMed  CAS  Google Scholar 

  133. Schuchardt A, D’Agati V, Larsson-Blomberg L et al. Defects in the kidney and nervous system of mice lacking the receptor tyrosine kinase receptor Ret. Nature 1994;367:380–383.

    Article  PubMed  CAS  Google Scholar 

  134. Schuchardt A, D’Agati V, Pachnis V et al. Renal agenesis and hypodysplasia in ret-k-. mutant mice result from defects in ureteric bud development. Development 1996;122:1919–1929.

    PubMed  CAS  Google Scholar 

  135. Moore MW, Klein RD, Farinas I et al. Renal and neuronal abnormalities in mice lacking GDNF. Nature 1996;382:76–79.

    Article  PubMed  CAS  Google Scholar 

  136. Pichel JG, Shen L, Sheng HZ et al. Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 1996;382:73–76.

    Article  PubMed  CAS  Google Scholar 

  137. Sanchez MP, Silos-Santiago I, Frisen J et al. Renal agenesis and the absence of enteric neurones in mice lacking GDNF. Nature 1996;382:70–73.

    Article  PubMed  CAS  Google Scholar 

  138. Towers PR, Woolf AS, Hardman P. Glial cell line-derived neurotrophic factor stimulates ureteric bud outgrowth and enhances survival of ureteric bud cells in vitro. Exp Nephrol 1998;6:337–351.

    Article  PubMed  CAS  Google Scholar 

  139. O’Rourke DA, Sakurai H, Spokes K, Kjelsberg C, Takahashi M, Nigam S, Cantley L. Expression of c-ret promotes morphogenesis and cell survival in mIMCD-3 cells. Am J Physiol 1999;276:F581–F588.

    PubMed  Google Scholar 

  140. Skinner MA, Safford SD, Reeves JG, Jackson ME, Freemerman AJ. Renal aplasia in humans is associated with RET mutations. Am J Hum Genet 2008;82:344–351.

    Article  PubMed  CAS  Google Scholar 

  141. Yang Y, Houle AM, Letendre J, Richter A. RET Gly691Ser mutation is associated with primary vesicoureteral reflux in the French-Canadian population from Quebec. Hum Mutat 2008;29:695–702.

    Article  PubMed  CAS  Google Scholar 

  142. Basson MA, Watson-Johnson J, Shakya R, Akbulut S, Hyink D, Costantini FD, Wilson PD, Mason IJ, Licht JD. Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1. Dev Biol 2006 15;299:466–477.

    Article  PubMed  CAS  Google Scholar 

  143. 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. Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev Cell 2005;8:229–239.

    Article  PubMed  CAS  Google Scholar 

  144. Grieshammer U, Le Ma, Plump AS, Wang F, Tessier-Lavigne M, Martin GR. SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev Cell 2004;6:709–717.

    Article  PubMed  CAS  Google Scholar 

  145. 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. Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. Am J Hum Genet 2007;80:616–632.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  147. Michos O, Gonçalves A, Lopez-Rios J, Tiecke E, Naillat F, Beier K, Galli A, Vainio S, Zeller R. Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Development 2007;134:2397–405.

    Article  PubMed  CAS  Google Scholar 

  148. Qiao J, Uzzo R, Obara-Ishihara T, Degenstein L, Fuchs E, Herzlinger D. FGF-7 modulates ureteric bud growth and nephron number in the developing kidney. Development 1999;126:547–554.

    PubMed  CAS  Google Scholar 

  149. Woolf AS, Kolatsi-Joannou M, Hardman P, Andermarcher E, Moorby C, Fine LG, Jat PS, Noble MD, Gherardi E. Roles of hepatocyte growth factor/scatter factor and the met receptor in the early development of the metanephros. J Cell Biol 1995;128:171–184.

    Article  PubMed  CAS  Google Scholar 

  150. Majumdar A, Vainio S, Kispert A, McMahon J, McMahon AP. Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 2003;130:3175–3185.

    Article  PubMed  CAS  Google Scholar 

  151. Esquela AF, Lee SJ. Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol 2003;257:356–370.

    Article  PubMed  CAS  Google Scholar 

  152. Ostrom L, Tang MJ, Gruss P, Dressler GR. Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease. Dev Biol 2000;219:250–258.

    Article  PubMed  CAS  Google Scholar 

  153. Clarke JC, Patel SR, Raymond RM Jr, Andrew S, Robinson BG, Dressler GR, Brophy PD. Regulation of c-Ret in the developing kidney is responsive to Pax2 gene dosage. Hum Mol Genet 2006;15:3420–3428.

    Article  PubMed  CAS  Google Scholar 

  154. Brophy PD, Ostrom L, Lang KM, Dressler GR. Regulation of ureteric bud outgrowth by Pax2-dependent activation of the glial derived neurotrophic factor gene. Development 2001;128:4747–4756.

    PubMed  CAS  Google Scholar 

  155. Bridgewater D, Cox B, Cain J, Lau A, Athaide V, Gill PS, Kuure S, Sainio K, Rosenblum ND. Canonical WNT/β-catenin signaling is required for ureteric branching. Dev Biol 2008;317:83–94.

    Article  PubMed  CAS  Google Scholar 

  156. Santos OFP, Nigam SK. HGF-induced tubulogenesis and branching of epithelial cells is modulated by extracellular matrix and TGF-β. Dev Biol 1993;160:293–302.

    Article  PubMed  CAS  Google Scholar 

  157. Sakurai H, Nigam SK. Transforming growth factor-β selectively inhibits branching morphogenesis but not tubulogenesis. Am J Physiol 1997;410:F139–F146.

    Google Scholar 

  158. Linton JM, Martin GR, Reichardt LF. The ECM protein nephronectin promotes kidney development via integrin α8β1-mediated stimulation of Gdnf expression. Development 2007;134:2501–2509.

    Article  PubMed  CAS  Google Scholar 

  159. Hardelin JP, Julliard AK, Moniot B, Soussi-Yanicostas N, Verney C, Schwanzel-Fukuda M, Ayer-Le Lievre C, Petit C. Anosmin-1 is a regionally restricted component of basement membranes and interstitial matrices during organogenesis: implications for the developmental anomalies of X chromosome-linked Kallmann syndrome. Dev Dyn 1999;215:26–44.

    Article  PubMed  CAS  Google Scholar 

  160. Duke V, Quinton R, Gordon I, Bouloux PM, Woolf AS. Proteinuria, hypertension and chronic renal failure in X-linked Kallmann’s syndrome, a defined genetic cause of solitary functioning kidney. Nephrol Dial Transplant 1998;13:1998–2003.

    Article  PubMed  CAS  Google Scholar 

  161. McGregor L, Makela V, Darling SM, Vrontou S, Chalepakis G, Roberts C, Smart N, Rutland P, Prescott N, Hopkins J, Bentley E, Shaw A, Roberts E, Mueller R, Jadeja S, Philip N, Nelson J, Francannet C, Perez-Aytes A, Megarbane A, Kerr B, Wainwright B, Woolf AS, Winter RM, Scambler PJ. Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet 2003;34:203–208.

    Article  PubMed  CAS  Google Scholar 

  162. Jadeja S, Smyth I, Pitera JE, Taylor MS, van Haelst M, Bentley E, McGregor L, Hopkins J, Chalepakis G, Philip N, Perez-Aytes A, Watt FM, Darling SM, Jackson I, Woolf AS, Scambler PJ. Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs. Nat Genet 2005;37:520–525.

    Article  PubMed  CAS  Google Scholar 

  163. Kiyozumi D, Sugimoto N, Sekiguchi K. Breakdown of the reciprocal stabilization of QBRICK/Frem1, Fras1, and Frem2 at the basement membrane provokes Fraser syndrome-like defects. Proc Natl Acad Sci USA 2006;103:11981–11986.

    Article  PubMed  CAS  Google Scholar 

  164. Pitera JE, Scambler PJ, Woolf AS. Fras 1, a basement membrane-associated protein mutated in Fraser syndrome, mediates both the initiation of the mammalian kidney and the integrity of renal glomeruli. Hum Mol Genet 2008;17:3953–3964.

    Google Scholar 

  165. Karihaloo A, Karumanchi SA, Barasch J, Jha V, Nickel CH, Yang J, Grisaru S, Bush KT, Nigam S, Rosenblum ND, Sukhatme VP, Cantley LG. Endostatin regulates branching morphogenesis of renal epithelial cells and ureteric bud. Proc Natl Acad Sci USA 2001;98:12509–12514.

    Article  PubMed  CAS  Google Scholar 

  166. Hartwig S, Hu MC, Cella C, Piscione T, Filmus J, Rosenblum ND. Glypican-3 modulates inhibitory Bmp2-Smad signaling to control renal development in vivo. Mech Dev 2005;122:928–938.

    Article  PubMed  CAS  Google Scholar 

  167. Pilia G, Hughes-Benzie RM, MacKenzie A et al. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet 1996;12:241–247.

    Article  PubMed  CAS  Google Scholar 

  168. Evan AP, Satlin LM, Gattone II VH et al. Postnatal maturation of rabbit renal collecting duct. II. Morphological observations. Am J Physiol 1991;261:F91–F107.

    PubMed  CAS  Google Scholar 

  169. Fejes-Toth G, Naray-Fejes-Toth A. Differentiation of renal α-intercalated cells to β-intercalated and principal cells in culture. Proc Natl Acad Sci USA 1992;89:5487–5491.

    Article  PubMed  CAS  Google Scholar 

  170. Slotkin TA, Seidler FJ, Kavlock RJ et al. Fetal dexamethasone exposure accelerates development of renal function: relationship to dose, cell differentiation and growth inhibition. J Dev Physiol 1992;17:55–61.

    PubMed  CAS  Google Scholar 

  171. Avner ED, Sweeney WE, Nelson WJ. Abnormal sodium pump distribution during renal tubulogenesis in congenital murine polycystic kidney disease. Proc Natl Acad Sci USA 1992;89:7447–7451.

    Article  PubMed  CAS  Google Scholar 

  172. Bullock SL, Johnson T, Bao Q, Winyard PJD, Hughes RC, Woolf AS. Galectin-3 modulates ureteric bud branching in organ culture of the developing mouse kidney. J Am Soc Nephrol 2001;12:515–523.

    PubMed  CAS  Google Scholar 

  173. Winyard PJD, Bao Q, Hughes RC et al. Epithelial galectin-3 during human nephrogenesis and childhood cystic diseases. J Am Soc Nephrol 1997;8:1647–1657.

    PubMed  CAS  Google Scholar 

  174. Chiu MG, Johnson TM, Woolf AS, Dahm-Vicker EM, Long DA, Guay-Woodford L, Hillman KA, Bawumia S, Venner K, Hughes RC, Poirier F, Winyard PJ. Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease. Am J Pathol 2006;169:1925–1938.

    Article  PubMed  CAS  Google Scholar 

  175. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 2003;33:129–37.

    Article  PubMed  CAS  Google Scholar 

  176. Torkko JM, Manninen A, Schuck S, Simons K. Depletion of apical transport proteins perturbs epithelial cyst formation and ciliogenesis. J Cell Sci 2008;121:1193–1203.

    Article  PubMed  CAS  Google Scholar 

  177. Hikita C, Vijayakumar S, Takito J, Erdjument-Bromage H, Tempst P, Al-Awqati Q. Induction of terminal differentiation in epithelial cells requires polymerization of hensin by galectin 3. J Cell Biol 2000;151:1235–1246.

    Article  PubMed  CAS  Google Scholar 

  178. Geng L, Segay Y, Peissel B et al. Identification and localisation of polycystin, the PKD1 gene product. J Clin Invest 1996;2674–2683.

    Google Scholar 

  179. Fan H, Harrell JR, Dipp S, Saifudeen Z, El-Dahr SS. A novel pathological role of p53 in kidney development revealed by gene-environment interactions. Am J Physiol Renal Physiol 2005;288:F98–F107.

    Article  PubMed  CAS  Google Scholar 

  180. Gresh L, Fischer E, Reimann A, Tanguy M, Garbay S, Shao X, Hiesberger T, Fiette L, Igarashi P, Yaniv M, Pontoglio M. A transcriptional network in polycystic kidney disease. EMBO J 2004;23:1657–1668.

    Article  PubMed  CAS  Google Scholar 

  181. Fischer E, Legue E, Doyen A, Nato F, Nicolas JF, Torres V, Yaniv M, Pontoglio M. Defective planar cell polarity in polycystic kidney disease. Nat Genet 2006;38:21–23.

    Article  PubMed  CAS  Google Scholar 

  182. Van Bodegom D, Saifudeen Z, Dipp S, Puri S, Magenheimer BS, Calvet JP, El-Dahr SS. The polycystic kidney disease-1 gene is a target for p53-mediated transcriptional repression. J Biol Chem 2006;281:31234–31244.

    Article  PubMed  CAS  Google Scholar 

  183. Kolatsi-Joannou M, Bingham C, Ellard S, Bulman MP, Allen LIS, Hattersley AT, Woolf AS. Hepatocyte nuclear factor 1β: a new kindred with renal cysts and diabetes, and gene expression in normal human development. J Am Soc Nephrol 2001;12:2175–2180.

    PubMed  CAS  Google Scholar 

  184. Bingham C, Ellard S, van’t Hoff WG, Simmonds HA, Marinaki AM, Badman MK, Winocour PH, Stride A, Lockwood CR, Nicholls AJ, Owen KR, Spyer G, Pearson ER, Hattersley AT. nAtypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1b gene mutation. Kidney Int 2003;63:1645–1651.

    Article  PubMed  CAS  Google Scholar 

  185. Adalat S, Woolf AS, Johnstone KA, Wirsing A, Harries LW, Long DA, Hennekam RC, Ledermann SE, Rees L, van’t Hoff W, Marks SD, Trompeter RS, Tullus K, Winyard PJ, Cansick J, Mushtaq I, Dhillon HK, Bingham C, Edghill EL, Ellard S, Shroff R, Stanescu H, Ryffel G, Bockenhauer D. Hepatocyte Nuclear Factor 1B mutations are associated with hypomagnesemia and renal magnesium wasting. J AM Soc Nephrol, in press.

    Google Scholar 

  186. Sariola H, Aufderheide E, Bernhard H et al. Antibodies to cell surface ganglioside GD3 perturb inductive epithelial-mesenchymal interactions. Cell 1988;54:235–245.

    Article  PubMed  CAS  Google Scholar 

  187. Schmidt-Ott KM, Chen X, Paragas N, Levinson RS, Mendelsohn CL, Barasch J. c-kit delineates a distinct domain of progenitors in the developing kidney. Dev Biol 2006;299:238–249.

    Article  PubMed  CAS  Google Scholar 

  188. Hatini V, Huh SO, Herzlinger D et al. Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of Winged Helix transcription factor BF-2. Genes Dev 1996;10:1467–1478.

    Article  PubMed  CAS  Google Scholar 

  189. Batourina E, Gim S, Bello N, Shy M, Clagett-Dame M, Srinivas S, Costantini F, Mendelsohn C. Vitamin A controls epithelial/mesenchymal interactions through Ret expression. Nat Genet 2001;27:74–78.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  191. Karavanov A, Sainio K, Palgi J et al. Neurotrophin-3 rescues neuronal precursors from apoptosis and promotes neuronal differentiation in the embryonic metanephric kidney. Proc Natl Acad Sci USA 1995;92:11279–11280.

    Article  PubMed  CAS  Google Scholar 

  192. Sariola H, Ekblom P, Henke-Fahle S. Embryonic neurons as in vitro inducers of differentiation of nephrogenic mesenchyme. Dev Biol 1989;132:271–281.

    Article  PubMed  CAS  Google Scholar 

  193. Sariola H, Holm K, Henke-Fahle S. Early innervation of the metanephric kidney. Development 1988;104:563–589.

    Google Scholar 

  194. Dravis C, Yokoyama N, Chumley MJ, Cowan CA, Silvany RE, Shay J, Baker LA, Henkemeyer M. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev Biol 2004;271:272–290.

    Article  PubMed  CAS  Google Scholar 

  195. Mo R, Kim JH, Zhang J, Chiang C, Hui CC, Kim PC. Anorectal malformations caused by defects in sonic hedgehog signaling. Am J Pathol 2001;159:765–774.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  198. Haraguchi R, Motoyama J, Sasaki H, Satoh Y, Miyagawa S, Nakagata N, Moon A, Yamada G. Molecular analysis of coordinated bladder and urogenital organ formation by hedgehog signaling. Development 2007;134:525–533.

    Article  PubMed  CAS  Google Scholar 

  199. Jenkins D, Winyard PJ, Woolf AS. Immunohistochemical analysis of Sonic hedgehog signalling in normal human urinary tract development. J Anat 2007;211:620–629.

    Article  PubMed  CAS  Google Scholar 

  200. Shiroyanagi Y, Liu B, Cao M, Agras K, Li J, Hsieh MH, Willingham EJ, Baskin LS. Urothelial sonic hedgehog signaling plays an important role in bladder smooth muscle formation. Differentiation 2007;75:968–977.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  204. Miyazaki Y, Tsuchida S, Nishimura H, Pope JC 4th, Harris RC, McKanna JM, Inagami T, Hogan BL, Fogo A, Ichikawa I. Angiotensin induces the urinary peristaltic machinery during the perinatal period. J Clin Invest 1998;102:1489–1497.

    Article  PubMed  CAS  Google Scholar 

  205. Funjinaka H, Mijazaki Y, Matsusaka T, Yoshida H, Fogo AB, Inaga T, Ichikawa I. Salutary role for angiotensin in partial urinary tract obstruction. Kidney Int 2000;58:2018–2027.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  207. Yi ES, Shabaik AS, Lacey DL et al. Keratinocyte growth factor causes proliferation of urothelium in vivo. J Urol 1995;154:1566–1570.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  209. Jenkins D, Bitner-Glindzicz M, Malcolm S, Hu CC, Allison J, Winyard PJ, Gullett AM, Thomas DF, Belk RA, Feather SA, Sun TT, Woolf AS. De novo Uroplakin IIIa heterozygous mutations cause human renal adysplasia leading to severe kidney failure. J Am Soc Nephrol 2005;16:2141–2149.

    PubMed  CAS  Google Scholar 

  210. Jenkins D, Woolf AS. Uroplakins: new molecular players in the biology of urinary tract malformations. Kidney Int 2007;71:195–200.

    Article  PubMed  CAS  Google Scholar 

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Woolf, A.S., Pitera, J.E. (2009). Embryology. In: Avner, E., Harmon, W., Niaudet, P., Yoshikawa, N. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-76341-3_1

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  • DOI: https://doi.org/10.1007/978-3-540-76341-3_1

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