Abstract
Renal anomalies are common birth defects that may manifest as a wide spectrum of anomalies from hydronephrosis (dilation of the renal pelvis and calyces) to renal aplasia (complete absence of the kidney(s)). Aneuploidies and mosaicisms are the most common syndromes associated with CAKUT. Syndromes with single gene and renal developmental defects are less common but have facilitated insight into the mechanism of renal and other organ development. Analysis of underlying genetic mutations with transgenic and mutant mice has also led to advances in our understanding of mechanisms of renal development.
References
Aguinaga M, Zenteno JC, Perez-Cano H, Moran V (2010) Sonic hedgehog mutation analysis in patients with VACTERL association. Am J Med Genet Part A 152a:781–783. doi:10.1002/ajmg.a.33293
Altug-Teber O et al (2007) Specific transcriptional changes in human fetuses with autosomal trisomies. Cytogenet Genome Res 119:171–184. doi:10.1159/000112058
Basson MA et al (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. doi:10.1016/j.ydbio.2006.08.051
Basta JM, Robbins L, Kiefer SM, Dorsett D, Rauchman M (2014) Sall1 balances self-renewal and differentiation of renal progenitor cells. Development 141:1047–1058. doi:10.1242/dev.095851
Bates CM (2011) Role of fibroblast growth factor receptor signaling in kidney development. Am J Physiol Renal Physiol 301:F245–F251. doi:10.1152/ajprenal.00186.2011
Bernard P, Harley VR (2007) Wnt4 action in gonadal development and sex determination. Int J Biochem Cell Biol 39:31–43. doi:10.1016/j.biocel.2006.06.007
Bernard P, Sim H, Knower K, Vilain E, Harley V (2008) Human SRY inhibits beta-catenin-mediated transcription. Int J Biochem Cell Biol 40:2889–2900. doi:10.1016/j.biocel.2008.06.006
Berthon A, Martinez A, Bertherat J, Val P (2012) Wnt/beta-catenin signalling in adrenal physiology and tumour development. Mol Cell Endocrinol 351:87–95. doi:10.1016/j.mce.2011.09.009
Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ (2004) A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46,XX woman. N Engl J Med 351:792–798. doi:10.1056/NEJMoa040533
Biason-Lauber A et al (2007) WNT4 deficiency—a clinical phenotype distinct from the classic Mayer–Rokitansky–Kuster–Hauser syndrome: a case report. Hum Reprod 22:224–229. doi:10.1093/humrep/del360
Bingham C et al (2001) Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease. Am J Hum Genet 68:219–224. doi:10.1086/316945
Blake J, Rosenblum ND (2014) Renal branching morphogenesis: morphogenetic and signaling mechanisms. Semin Cell Dev Biol 36:2–12. doi:10.1016/j.semcdb.2014.07.011
Bonnet CS et al (2009) Defects in cell polarity underlie TSC and ADPKD-associated cystogenesis. Hum Mol Genet 18:2166–2176. doi:10.1093/hmg/ddp149
Botto LD et al (1997) The spectrum of congenital anomalies of the VATER association: an international study. Am J Med Genet 71:8–15
Bridgewater D et al (2008) Canonical WNT/beta-catenin signaling is required for ureteric branching. Dev Biol 317:83–94. doi:10.1016/j.ydbio.2008.02.010
Brook-Carter PT et al (1994) Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease—a contiguous gene syndrome. Nat Genet 8:328–332. doi:10.1038/ng1294-328
Brosens E et al (2013) VACTERL association etiology: the impact of de novo and rare copy number variations. Mol Syndromol 4:20–26. doi:10.1159/000345577
Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP (2005) Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell 9:283–292. doi:10.1016/j.devcel.2005.05.016
Caruana G et al (2015) Copy-number variation associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 30:487–495. doi:10.1007/s00467-014-2962-9
Chassot AA et al (2011) RSPO1/β-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary. PLoS One 6. doi:10.1371/journal.pone.0025641
Chatterjee R et al (2012) Traditional and targeted exome sequencing reveals common, rare and novel functional deleterious variants in RET-signaling complex in a cohort of living US patients with urinary tract malformations. Hum Genet 131:1725–1738. doi:10.1007/s00439-012-1181-3
Chen L, Deng CX (2005) Roles of FGF signaling in skeletal development and human genetic diseases. Front Biosci J Virtual Libr 10:1961–1976
Chen R, Amoui M, Zhang Z, Mardon G (1997) Dachshund and eyes absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell 91:893–903
Cheng HT et al (2003) Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney. Development 130:5031–5042. doi:10.1242/dev.00697
Clissold RL, Hamilton AJ, Hattersley AT, Ellard S, Bingham C (2014) HNF1B-associated renal and extra-renal disease—an expanding clinical spectrum. Nat Rev Nephrol 11:102–112. doi:10.1038/nrneph.2014.232
Costantini F (2010) GDNF/Ret signaling and renal branching morphogenesis: from mesenchymal signals to epithelial cell behaviors. Organogenesis 6:252–262. doi:10.4161/org.6.4.12680
Costantini F, Shakya R (2006) GDNF/Ret signaling and the development of the kidney. Bioessays 28:117–127. doi:10.1002/bies.20357
Crino PB, Nathanson KL, Henske EP (2006) The tuberous sclerosis complex. N Engl J Med 355:1345–1356. doi:10.1056/NEJMra055323
Dibble CC et al (2012) TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1. Mol Cell 47:535–546. doi:10.1016/j.molcel.2012.06.009
DiMario FJ, Sahin M, Ebrahimi-Fakhari D (2015) Tuberous sclerosis complex. Pediatr Clin N Am 62:633–648. doi:10.1016/j.pcl.2015.03.005
Dixon BP, Hulbert JC, Bissler JJ (2011) Tuberous sclerosis complex renal disease. Nephron Exp Nephrol 118:e15–e20. doi:10.1159/000320891
Edghill EL, Bingham C, Ellard S, Hattersley AT (2006) Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 43:84–90. doi:10.1136/jmg.2005.032854
Gillick J, Mooney E, Giles S, Bannigan J, Puri P (2003) Notochord anomalies in the adriamycin rat model: a morphologic and molecular basis for the VACTERL association. J Pediatr Surg 38, 469–473; discussion 469–473. doi:10.1053/jpsu.2003.50081
Gresh L et al (2004) A transcriptional network in polycystic kidney disease. EMBO J 23:1657–1668. doi:10.1038/sj.emboj.7600160
Guo Q et al (2015) Adam10 mediates the choice between principal cells and intercalated cells in the kidney. J Am Soc Nephrol JASN 26:149–159. doi:10.1681/asn.2013070764
Hains DS et al (2010) High incidence of vesicoureteral reflux in mice with Fgfr2 deletion in kidney mesenchyma. J Urol 183:2077–2084. doi:10.1016/j.juro.2009.12.095
Handrigan GR et al (2013) Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation. J Med Genet 50:163–173. doi:10.1136/jmedgenet-2012-101288
Harrison SJ, Nishinakamura R, Monaghan AP (2008) Sall1 regulates mitral cell development and olfactory nerve extension in the developing olfactory bulb. Cereb Cortex (New York, N.Y.: 1991) 18:1604–1617. doi:10.1093/cercor/bhm191
Hartman TR et al (2009) The tuberous sclerosis proteins regulate formation of the primary cilium via a rapamycin-insensitive and polycystin 1-independent pathway. Hum Mol Genet 18:151–163. doi:10.1093/hmg/ddn325
Heidet L et al (2010) Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol CJASN 5:1079–1090. doi:10.2215/cjn.06810909
Hilger A et al (2013) De novo microduplications at 1q41, 2q37.3, and 8q24.3 in patients with VATER/VACTERL association. Eur J Hum Genet EJHG 21:1377–1382. doi:10.1038/ejhg.2013.58
Hill P, Wang B, Ruther U (2007) The molecular basis of Pallister Hall associated polydactyly. Hum Mol Genet 16:2089–2096. doi:10.1093/hmg/ddm156
Hines EA et al (2016) Syndactyly in a novel Fras1(rdf) mutant results from interruption of signals for interdigital apoptosis. Dev Dyn Off Publ Am Assoc Anat 245:497–507. doi:10.1002/dvdy.24389
Hofmann AD, Duess JW, Puri P (2014) Congenital anomalies of the kidney and urinary tract (CAKUT) associated with Hirschsprung’s disease: a systematic review. Pediatr Surg Int 30:757–761. doi:10.1007/s00383-014-3529-3
Horikawa Y et al (1997) Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 17:384–385. doi:10.1038/ng1297-384
Hoskins BE et al (2007) Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. Am J Hum Genet 80:800–804. doi:10.1086/513322
Hwang DY et al (2014) Mutations in 12 known dominant disease-causing genes clarify many congenital anomalies of the kidney and urinary tract. Kidney Int 85:1429–1433. doi:10.1038/ki.2013.508
Iglesias DM et al (2007) Canonical WNT signaling during kidney development. Am J Physiol Renal Physiol 293:F494–F500. doi:10.1152/ajprenal.00416.2006
Inoki K, Li Y, Zhu T, Wu J, Guan K-L (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4:648–657. doi:10.1038/ncb839
Iwasaki N et al (1998) Liver and kidney function in Japanese patients with maturity-onset diabetes of the young. Diabetes Care 21:2144–2148
Jeanpierre C et al (2011) RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects. J Med Genet 48:497–504. doi:10.1136/jmg.2010.088526
Kakkar N, Menon S, Radotra BD (2006) Histomorphology of renal dysplasia—an autopsy study. Fetal Pediatr Pathol 25:73–86. doi:10.1080/15513810600788764
Kamath BM, Spinner NB, Rosenblum ND (2013) Renal involvement and the role of Notch signalling in Alagille syndrome. Nat Rev Nephrol 9:409–418. doi:10.1038/nrneph.2013.102
Kamath BM et al (2012) Renal anomalies in Alagille syndrome: a disease-defining feature. Am J Med Genet A 158A:85–89. doi:10.1002/ajmg.a.34369
Kanda S et al (2014) Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor. J Am Soc Nephrol JASN 25:2584–2595. doi:10.1681/asn.2013080896
Kiefer SM et al (2003) Expression of a truncated Sall1 transcriptional repressor is responsible for Townes–Brocks syndrome birth defects. Hum Mol Genet 12:2221–2227. doi:10.1093/hmg/ddg233
Kiefer SM et al (2010) Sall1-dependent signals affect Wnt signaling and ureter tip fate to initiate kidney development. Development 137:3099–3106. doi:10.1242/dev.037812
Kim J, Kim P, Hui CC (2001a) The VACTERL association: lessons from the Sonic hedgehog pathway. Clin Genet 59:306–315
Kim PC, Mo R, Hui CC (2001b) Murine models of VACTERL syndrome: role of sonic hedgehog signaling pathway. J Pediatr Surg 36:381–384
Kingswood JC et al (2016) Review of the tuberous sclerosis renal guidelines from the 2012 consensus conference: current data and future study. Nephron 133. doi:10.1159/000448293
Kohl S et al (2014) Mild recessive mutations in six Fraser syndrome-related genes cause isolated congenital anomalies of the kidney and urinary tract. J Am Soc Nephrol JASN 25:1917–1922. doi:10.1681/asn.2013101103
Kohlhase J (1993) In: Pagon RA et al (eds) GeneReviews(R). University of Washington, Seattle University of Washington, Seattle
Kolatsi-Joannou M et al (2001) Hepatocyte nuclear factor-1beta: a new kindred with renal cysts and diabetes and gene expression in normal human development. J Am Soc Nephrol JASN 12:2175–2180
Kopan R (2012) Notch signaling. Cold Spring Harb Perspect Biol 4:a011213. doi:10.1101/cshperspect.a011213
Krebs LT et al (2000) Notch signaling is essential for vascular morphogenesis in mice. Genes Dev 14:1343–1352
Krueger DA et al (2010) Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med 363:1801–1811. doi:10.1056/NEJMoa1001671
Lahiri D et al (2007) Nephropathy and defective spermatogenesis in mice transgenic for a single isoform of the Wilms’ tumour suppressor protein, WT1-KTS, together with one disrupted Wt1 allele. Mol Reprod Dev 74:300–311. doi:10.1002/mrd.20491
Landgraf K et al (2010) Sipl1 and Rbck1 are novel Eya1-binding proteins with a role in craniofacial development. Mol Cell Biol 30:5764–5775. doi:10.1128/mcb.01645-09
Lefebvre J et al (2015) Alternatively spliced isoforms of WT1 control podocyte-specific gene expression. Kidney Int 88:321–331. doi:10.1038/ki.2015.140
Li Y, Manaligod J, Weeks D (2010) EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis. Biol Cell 102:277–292. doi:10.1042/bc20090098
Lokmane L, Heliot C, Garcia-Villalba P, Fabre M, Cereghini S (2010) vHNF1 functions in distinct regulatory circuits to control ureteric bud branching and early nephrogenesis. Development 137:347–357. doi:10.1242/dev.042226
Lopez-Rios J et al (2012) GLI3 constrains digit number by controlling both progenitor proliferation and BMP-dependent exit to chondrogenesis. Dev Cell 22:837–848. doi:10.1016/j.devcel.2012.01.006
Lubinsky M (2015) The VACTERL Association as a disturbance of cell fate determination. Am J Med Genet Part A 167a:2582–2588. doi:10.1002/ajmg.a.37238
Madariaga L et al (2013) Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes. Clin J Am Soc Nephrol CJASN 8:1179–1187. doi:10.2215/cjn.10221012
Mandel H et al (2008) SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet 82:39–47. doi:10.1016/j.ajhg.2007.08.005
Mao Z, Chong J, Ong ACM (2016) Autosomal dominant polycystic kidney disease: recent advances in clinical management. F1000Research 5. doi:10.12688/f1000research.9045.1
Marie PJ, Coffin JD, Hurley MM (2005) FGF and FGFR signaling in chondrodysplasias and craniosynostosis. J Cell Biochem 96:888–896. doi:10.1002/jcb.20582
Martucciello G, Ceccherini I, Lerone M, Jasonni V (2000) Special basic science review: pathogenesis of Hirschsprung’s disease. J Pediatr Surg 35:1017–1025. doi:10.1053/jpsu.2000.7763
Materna-Kiryluk A et al (2014) The emerging role of genomics in the diagnosis and workup of congenital urinary tract defects: a novel deletion syndrome on chromosome 3q13.31-22.1. Pediatr Nephrol 29:257–267. doi:10.1007/s00467-013-2625-2
McCright B (2003) Notch signaling in kidney development. Curr Opin Nephrol Hypertens 12:5–10. doi:10.1097/01.mnh.0000049802.69874.c0
McCright B et al (2001) Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development 128:491–502
Mendel DB, Hansen LP, Graves MK, Conley PB, Crabtree GR (1991) HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev 5:1042–1056
Michos O et al (2010) Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet 6:e1000809. doi:10.1371/journal.pgen.1000809
Morita Y et al (2016) Sall1 transiently marks undifferentiated heart precursors and regulates their fate. J Mol Cell Cardiol 92:158–162. doi:10.1016/j.yjmcc.2016.02.008
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. doi:10.1152/ajprenal.00597.2007
Munger SC, Natarajan A, Looger LL, Ohler U, Capel B (2013) Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination. PLoS Genet 9. doi:10.1371/journal.pgen.1003630
North American Pediatric Renal Trials and Collaborative Studies (2011) NAPRTCS 2011 annual dialysis report. The National Institute of Diabetes and Digestive and Kidney Diseases, pp 1–26
Natarajan D, Marcos-Gutierrez C, Pachnis V, de Graaff E (2002) Requirement of signalling by receptor tyrosine kinase RET for the directed migration of enteric nervous system progenitor cells during mammalian embryogenesis. Development 129:5151–5160
Ngan ES, Kim KH, Hui CC (2013) Sonic hedgehog signaling and VACTERL association. Mol Syndromol 4:32–45. doi:10.1159/000345725
Nishinakamura R et al (2001) Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development 128:3105–3115
Nishita M et al (2014) Role of Wnt5a-Ror2 signaling in morphogenesis of the metanephric mesenchyme during ureteric budding. Mol Cell Biol 34:3096–3105. doi:10.1128/mcb.00491-14
O’Brien LL et al (2016) Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators. Development 143:595–608. doi:10.1242/dev.127175
Park JS et al (2012) Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev Cell 23:637–651. doi:10.1016/j.devcel.2012.07.008
Passos-Bueno MR et al (1999) Clinical spectrum of fibroblast growth factor receptor mutations. Hum Mutat 14:115–125. doi:10.1002/(sici)1098-1004(1999)14:2<115::aid-humu3>3.0.co;2-2
Patek CE et al (2003) Murine Denys–Drash syndrome: evidence of podocyte de-differentiation and systemic mediation of glomerulosclerosis. Hum Mol Genet 12:2379–2394. doi:10.1093/hmg/ddg240
Pavlakis E, Chiotaki R, Chalepakis G (2011) The role of Fras1/Frem proteins in the structure and function of basement membrane. Int J Biochem Cell Biol 43:487–495. doi:10.1016/j.biocel.2010.12.016
Pema M et al (2016) mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex. Nat Commun 7:10786. doi:10.1038/ncomms10786
Pignoni F et al (1997) The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell 91:881–891
Pini Prato A et al (2009) Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association. Medicine 88:83–90. doi:10.1097/MD.0b013e31819cf5da
Pitera JE, Scambler PJ, Woolf AS (2008) Fras1, 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 17:3953–3964. doi:10.1093/hmg/ddn297
Pitera JE, Woolf AS, Basson MA, Scambler PJ (2012) Sprouty1 haploinsufficiency prevents renal agenesis in a model of Fraser syndrome. J Am Soc Nephrol JASN 23:1790–1796. doi:10.1681/asn.2012020146
Plank TL, Yeung RS, Henske EP (1998) Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles. Cancer Res 58:4766–4770
Poladia DP et al (2006) Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. Dev Biol 291:325–339. doi:10.1016/j.ydbio.2005.12.034
Rakowski SK et al (2006) Renal manifestations of tuberous sclerosis complex: incidence, prognosis, and predictive factors. Kidney Int 70:1777–1782. doi:10.1038/sj.ki.5001853
Reidy KJ, Rosenblum ND (2009) Cell and molecular biology of kidney development. Semin Nephrol 29:321–337. doi:10.1016/j.semnephrol.2009.03.009
Riccio P, Cebrian C, Zong H, Hippenmeyer S, Costantini F (2016) Ret and Etv4 promote directed movements of progenitor cells during renal branching morphogenesis. PLoS Biol 14:e1002382. doi:10.1371/journal.pbio.1002382
Ruf RG et al (2004) SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1–SIX1–DNA complexes. Proc Natl Acad Sci USA 101:8090–8095. doi:10.1073/pnas.0308475101
Sadowski CE et al (2015) A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol JASN 26:1279–1289. doi:10.1681/asn.2014050489
Saisawat P et al (2014) Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association. Kidney Int 85:1310–1317. doi:10.1038/ki.2013.417
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. doi:10.1016/j.ydbio.2005.05.029
Sanna-Cherchi S et al (2012) Copy-number disorders are a common cause of congenital kidney malformations. Am J Hum Genet 91:987–997. doi:10.1016/j.ajhg.2012.10.007
Schneider J, Arraf AA, Grinstein M, Yelin R, Schultheiss TM (2015) Wnt signaling orients the proximal-distal axis of chick kidney nephrons. Development 142:2686–2695. doi:10.1242/dev.123968
Schuchardt A, D’Agati V, Pachnis V, Costantini F (1996) Renal agenesis and hypodysplasia in ret-k-mutant mice result from defects in ureteric bud development. Development 122:1919–1929
Seyedzadeh A, Kompani F, Esmailie E, Samadzadeh S, Farshchi B (2008) High-grade vesicoureteral reflux in Pfeiffer syndrome. Urol J 5:200–202
Shakya R, Watanabe T, Costantini F (2005) The role of GDNF/Ret signaling in ureteric bud cell fate and branching morphogenesis. Dev Cell 8:65–74. doi:10.1016/j.devcel.2004.11.008
Shillingford JM et al (2006) The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci USA 103:5466–5471. doi:10.1073/pnas.0509694103
Siroky BJ, Yin H, Bissler JJ (2011) Clinical and molecular insights into tuberous sclerosis complex renal disease. Pediatr Nephrol 26:839–852. doi:10.1007/s00467-010-1689-5
Si-Tayeb K, Lemaigre FP, Duncan SA (2010) Organogenesis and development of the liver. Dev Cell 18:175–189. doi:10.1016/j.devcel.2010.01.011
Song R, Yosypiv IV (2011) Genetics of congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 26:353–364. doi:10.1007/s00467-010-1629-4
Stark K, Vainio S, Vassileva G, McMahon AP (1994) Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372:679–683. doi:10.1038/372679a0
Stoll C, Dott B, Alembik Y, Roth MP (2014) Associated nonurinary congenital anomalies among infants with congenital anomalies of kidney and urinary tract (CAKUT). Eur J Med Genet 57:322–328. doi:10.1016/j.ejmg.2014.04.014
Stoll C, Dott B, Alembik Y, Roth MP (2015) Associated congenital anomalies among cases with Down syndrome. Eur J Med Genet 58:674–680. doi:10.1016/j.ejmg.2015.11.003
Su N, Jin M, Chen L (2014) Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models. Bone Res 2:14003. doi:10.1038/boneres.2014.3
Tadjuidje E, Hegde RS (2013) The eyes absent proteins in development and disease. Cell Mol Life Sci 70:1897–1913. doi:10.1007/s00018-012-1144-9
Taraviras S et al (1999) Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system. Development 126:2785–2797
Tee AR et al (2002) Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci USA 99:13571–13576. doi:10.1073/pnas.202476899
Thomas R et al (2011) HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatr Nephrol 26:897–903. doi:10.1007/s00467-011-1826-9
Uyttendaele H, Ho J, Rossant J, Kitajewski J (2001) Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium. Proc Natl Acad Sci USA 98:5643–5648. doi:10.1073/pnas.091584598
Vainio SJ (2003) Nephrogenesis regulated by Wnt signaling. J Nephrol 16:279–285
van Slegtenhorst M et al (1998) Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet 7:1053–1057
Verbitsky M et al (2015) Genomic imbalances in pediatric patients with chronic kidney disease. J Clin Invest 125:2171–2178. doi:10.1172/jci80877
Vivante A et al (2013) Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling. J Am Soc Nephrol JASN 24:550–558. doi:10.1681/asn.2012010097
Volckaert T, De Langhe SP (2015) Wnt and FGF mediated epithelial-mesenchymal crosstalk during lung development. Dev Dyn Off Publ Am Assoc Anat 244:342–366. doi:10.1002/dvdy.24234
Warthen DM et al (2006) Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat 27:436–443. doi:10.1002/humu.20310
Weber S et al (2006) Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J Am Soc Nephrol JASN 17:2864–2870. doi:10.1681/asn.2006030277
Weber S et al (2008) SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol JASN 19:891–903. doi:10.1681/asn.2006111282
Xi Q et al (2016) Copy number variations in multicystic dysplastic kidney: update for prenatal diagnosis and genetic counseling. Prenat Diagn. doi:10.1002/pd.4807
Xu PX, Cheng J, Epstein JA, Maas RL (1997) Mouse Eya genes are expressed during limb tendon development and encode a transcriptional activation function. Proc Natl Acad Sci USA 94:11974–11979
Xu PX et al (1999) Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet 23:113–117. doi:10.1038/12722
Xu J et al (2014) Eya1 interacts with Six2 and Myc to regulate expansion of the nephron progenitor pool during nephrogenesis. Dev Cell 31:434–447. doi:10.1016/j.devcel.2014.10.015
Xue Y et al (1999) Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1. Hum Mol Genet 8:723–730
Yoder BK, Hou X, Guay-Woodford LM (2002) The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol JASN 13:2508–2516
Zeidler C et al (2014) Heterozygous FGF8 mutations in patients presenting cryptorchidism and multiple VATER/VACTERL features without limb anomalies. Birth Defects Res A Clin Mol Teratol 100:750–759. doi:10.1002/bdra.23278
Zhao H et al (2004) Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol 276:403–415. doi:10.1016/j.ydbio.2004.09.002
Zou D, Silvius D, Rodrigo-Blomqvist S, Enerbäck S, Xu PX (2006) Eya1 regulates the growth of otic epithelium and interacts with Pax2 during the development of all sensory areas in the inner ear. Dev Biol 298. doi:10.1016/j.ydbio.2006.06.049
Zubkov VS et al (2015) A spatially-averaged mathematical model of kidney branching morphogenesis. J Theor Biol 379:24–37. doi:10.1016/j.jtbi.2015.04.015
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Pal, A., Reidy, K.J. (2017). Genetic Syndromes Affecting Kidney Development. In: Miller, R. (eds) Kidney Development and Disease. Results and Problems in Cell Differentiation, vol 60. Springer, Cham. https://doi.org/10.1007/978-3-319-51436-9_10
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