The Role of Notch Signaling in Kidney Development and Disease

  • Hila Barak
  • Kameswaran Surendran
  • Scott C. Boyle
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 727)

Abstract

The kidney is the body’s filter, responsible for the removal of metabolic waste and the excretion or reabsorption of electrolytes to control blood composition and pH balance. The functional unit of this filter is the nephron, whose segmented architecture has been largely conserved in form and function throughout eukaryotic evolution. Not surprisingly, the core developmental pathways that regulate the formation of the nephron have also been conserved. In particular, the Notch signaling pathway functions in both primitive and advanced nephrons to pattern domains required for the kidney’s diverse functions. In this chapter, we will discuss the role that Notch plays in directing cell fate decisions during embryonic development of the pronephros and metanephros. We will go on to discuss the later role of Notch signaling as a cyst-suppressor and the consequences of aberrant or absent Notch activity in disease and cancer. The work discussed here highlights the fundamental importance of Notch during development and homeostasis of the kidney and underlies the need for mechanistic understanding of its role towards the treatment of human disease.

Keywords

Glomerulosclerosis 

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References

  1. 1.
    Saxen L. Organogenesis of the kidney. Cambridge: Cambridge University Press; 1987.CrossRefGoogle Scholar
  2. 2.
    Grobstein C. Inductive epitheliomesenchymal interaction in cultured organ rudiments of the mouse. Science 1953; 118(3054):52–55.PubMedCrossRefGoogle Scholar
  3. 3.
    Drummond IA. The zebrafish pronephros: a genetic system for studies of kidney development. Pediatr Nephrol 2000; 14(5):428–435.PubMedCrossRefGoogle Scholar
  4. 4.
    Vize PD, Woolf AS, Bard JBL. The kidney: from normal development to congenital diseases. Amsterdam; Boston: Academic Press; 2002.Google Scholar
  5. 5.
    Raciti D, Reggiani L, Geffers L et al. Organization of the pronephric kidney revealed by large-scale gene expression mapping. Genome Biol 2008; 9(5):R84.PubMedCrossRefGoogle Scholar
  6. 6.
    Wingert RA, Davidson AJ. The zebrafish pronephros: a model to study nephron segmentation. Kidney Int 2008; 73(10):1120–1127.PubMedCrossRefGoogle Scholar
  7. 7.
    Boyle S, de Caestecker M. Role of transcriptional networks in coordinating early events during kidney development. Am J Physiol Renal Physiol 2006; 291(1):F1–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Dressler GR. The cellular basis of kidney development. Annu Rev Cell Dev Biol 2006; 22:509–529.PubMedCrossRefGoogle Scholar
  9. 9.
    Dressler GR. Advances in early kidney specification, development and patterning. Development. 2009; 136(23):3863–3874.PubMedCrossRefGoogle Scholar
  10. 10.
    Seufert DW, Brennan HC, DeGuire J et al. Developmental basis of pronephric defects in Xenopus body plan phenotypes. Dev Biol 1999; 215(2):233–242.PubMedCrossRefGoogle Scholar
  11. 11.
    Mauch TJ, Yang G, Wright M et al. Signals from trunk paraxial mesoderm induce pronephros formation in chick intermediate mesoderm. Dev Biol 2000; 220(1):62–75.PubMedCrossRefGoogle Scholar
  12. 12.
    James RG, Schultheiss TM. Patterning of the avian intermediate mesoderm by lateral plate and axial tissues. Dev Biol 2003; 253(1):109–124.PubMedCrossRefGoogle Scholar
  13. 13.
    Barak H, Rosenfelder L, Schultheiss TM et al. Cell fate specification along the anterior-posterior axis of the intermediate mesoderm. Dev Dyn 2005; 232(4):901–914.PubMedCrossRefGoogle Scholar
  14. 14.
    James RG, Schultheiss TM. Bmp signaling promotes intermediate mesoderm gene expression in a dose-dependent, cell-autonomous and translation-dependent manner. Dev Biol 2005; 288(1):113–125.PubMedCrossRefGoogle Scholar
  15. 15.
    Preger-Ben Noon E, Barak H, Guttmann-Raviv N et al. Interplay between activin and Hox genes determines the formation of the kidney morphogenetic field. Development 2009; 136(12):1995–2004.CrossRefGoogle Scholar
  16. 16.
    Vize PD, Jones EA, Pfister R. Development of the Xenopus pronephric system. Dev Biol 1995; 171(2):531–540.PubMedCrossRefGoogle Scholar
  17. 17.
    Wingert RA, Selleck R, Yu J et al. The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros. PLoS Genet 2007; 3(10):1922–1938.PubMedCrossRefGoogle Scholar
  18. 18.
    McLaughlin KA, Rones MS, Mercola M. Notch regulates cell fate in the developing pronephros. Dev Biol 2000; 227(2):567–580.PubMedCrossRefGoogle Scholar
  19. 19.
    Taelman V, Van Campenhout C, Solter M et al. The Notch-effector HRT1 gene plays a role in glomerular development and patterning of the Xenopus pronephros anlagen. Development 2006; 133(15):2961–2971.PubMedCrossRefGoogle Scholar
  20. 20.
    Naylor RW, Jones EA. Notch activates Wnt-4 signalling to control medio-lateral patterning of the pronephros. Development 2009; 136(21):3585–3595.PubMedCrossRefGoogle Scholar
  21. 21.
    Zecchin E, Conigliaro A, Tiso N et al. Expression analysis of jagged genes in zebrafish embryos. Dev Dyn 2005; 233(2):638–645.CrossRefGoogle Scholar
  22. 22.
    Smithers L, Haddon C, Jiang YJ et al. Sequence and embryonic expression of deltaC in the zebrafish. Mech Dev 2000; 90(1):119–123.PubMedCrossRefGoogle Scholar
  23. 23.
    Van Campenhout C, Nichane M, Antoniou A et al. Evi1 is specifically expressed in the distal tubule and duct of the Xenopus pronephros and plays a role in its formation. Dev Biol 2006; 294(1):203–219.PubMedCrossRefGoogle Scholar
  24. 24.
    Fischer A, Schumacher N, Maier M et al. The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev 2004; 18(8):901–911.PubMedCrossRefGoogle Scholar
  25. 25.
    Rones MS, Woda J, Mercola M et al. Isolation and characterization of Xenopus Hey-1: a downstream mediator of Notch signaling. Dev Dyn 2002; 225(4):554–560.PubMedCrossRefGoogle Scholar
  26. 26.
    Kopan R, Ilagan MX. The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism. Cell 2009; 137(2):216–233.PubMedCrossRefGoogle Scholar
  27. 27.
    Costantini F, Kopan R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell 18(5):698–712.Google Scholar
  28. 28.
    Boyle S, Misfeldt A, Chandler KJ et al. Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia. Dev Biol 2008; 313(1):234–245.PubMedCrossRefGoogle Scholar
  29. 29.
    Humphreys BD, Lin SL, Kobayashi A et al. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 176(1):85–97.Google Scholar
  30. 30.
    Kobayashi A, Valerius MT, Mugford JW et al. Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 2008; 3(2):169–181.PubMedCrossRefGoogle Scholar
  31. 31.
    Mugford JW, Sipila P, McMahon JA et al. Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney. Dev Biol 2008; 324(1):88–98.PubMedCrossRefGoogle Scholar
  32. 32.
    Georgas K, Rumballe B, Valerius MT et al. Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment. Dev Biol 2009; 332(2):273–286.PubMedCrossRefGoogle Scholar
  33. 33.
    Li L, Krantz ID, Deng Y et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet 1997; 16(3):243–251.PubMedCrossRefGoogle Scholar
  34. 34.
    Oda T, Elkahloun AG, Pike BL et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet 1997; 16(3):235–242.PubMedCrossRefGoogle Scholar
  35. 35.
    McDaniell R, Warthen DM, Sanchez-Lara PA et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet 2006; 79(1):169–173.PubMedCrossRefGoogle Scholar
  36. 36.
    Hamada Y, Kadokawa Y, Okabe M et al. Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development 1999; 126(15):3415–3424.PubMedGoogle Scholar
  37. 37.
    McCright B, Gao X, Shen L et al. Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development 2001; 128(4):491–502.Google Scholar
  38. 38.
    McCright B, Lozier J, Gridley T. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency. Development 2002; 129(4):1075–1082.PubMedGoogle Scholar
  39. 39.
    Chen L, Al-Awqati Q. Segmental expression of Notch and Hairy genes in nephrogenesis. Am J Physiol Renal Physiol 2005; 288(5):F939–952.PubMedGoogle Scholar
  40. 40.
    Leimeister C, Schumacher N, Gessler M. Expression of Notch pathway genes in the embryonic mouse metanephros suggests a role in proximal tubule development. Gene Expr Patterns 2003; 3(5):595–598.CrossRefGoogle Scholar
  41. 41.
    Piscione TD, Wu MY, Quaggin SE. Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis. Gene Expr Patterns 2004; 4(6):707–711.PubMedCrossRefGoogle Scholar
  42. 42.
    Cheng HT, Kim M, Valerius MT et al. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development 2007; 134(4):801–811.PubMedCrossRefGoogle Scholar
  43. 43.
    Surendran K, Boyle S, Barak H et al. The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. Dev Biol 2010; 337(2):386–395.PubMedCrossRefGoogle Scholar
  44. 44.
    Ong C, Cheng H, Chang LW et al. Target selectivity of vertebrate Notch proteins: collaboration between discrete domains and CSL binding site architecture determine activation probability. J Biol Chem 2006; 281(8):5106–5119.PubMedCrossRefGoogle Scholar
  45. 45.
    Cheng HT, Miner JH, Lin M et al. Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney. Development 2003; 130(20):5031–5042.PubMedCrossRefGoogle Scholar
  46. 46.
    Wang P, Pereira FA, Beasley D et al. Presenilins are required for the formation of comma-and S-shaped bodies during nephrogenesis. Development 2003; 130(20):5019–5029.PubMedCrossRefGoogle Scholar
  47. 47.
    Costantini F, Shakya R. GDNF/Ret signaling and the development of the kidney. Bioessays 2006; 28(2):117–127.PubMedCrossRefGoogle Scholar
  48. 48.
    Kuure S, Sainio K, Vuolteenaho R et al. Crosstalk between Jagged1 and GDNF/Ret/GFRalpha1 signalling regulates ureteric budding and branching. Mech Dev 2005; 122(6):765–780.Google Scholar
  49. 49.
    Kopan R, Ilagan MX. Gamma-secretase: proteasome of the membrane? Nat Rev Mol Cell Biol 2004; 5(6):499–504.PubMedCrossRefGoogle Scholar
  50. 50.
    Jeong HW, JU S, Koo BK et al. Inactivation of Notch signaling in the renal collecting duct causes nephrogenic diabetes insipidus in mice. J Clin Invest 2009; 119(11):3290–3300.PubMedGoogle Scholar
  51. 51.
    Koo BK, Yoon MJ, Yoon KJ et al. An obligatory role of mind bomb-1 in notch signaling of mammalian development. PLoS One 2007; 2(11):e1221.PubMedCrossRefGoogle Scholar
  52. 52.
    Liu Y, Pathak N, Kramer-Zucker A et al. Notch signaling controls the differentiation of transporting epithelia and multiciliated cells in the zebrafish pronephros. Development 2007; 134(6):1111–1122.PubMedCrossRefGoogle Scholar
  53. 53.
    Ma M, Jiang YJ. Jagged2a-notch signaling mediates cell fate choice in the zebrafish pronephric duct. PLoS Genet 2007; 3(1):e18.PubMedCrossRefGoogle Scholar
  54. 54.
    Blomqvist SR, Vidarsson H, Fitzgerald S et al. Distal renal tubular acidosis in mice that lack the forkhead transcription factor Foxi1. J Clin Invest 2004; 113(11):1560–1570.PubMedGoogle Scholar
  55. 55.
    Kurth I, Hentschke M, Hentschke S et al. The forkhead transcription factor Foxi1 directly activates the AE4 promoter. Biochem J 2006; 393(Pt 1):277–283.PubMedGoogle Scholar
  56. 56.
    Vidarsson H, Westergren R, Heglind M et al. The forkhead transcription factor Foxi1 is a master regulator of vacuolar H-ATPase proton pump subunits in the inner ear, kidney and epididymis. PLoS One 2009; 4(2):e4471.PubMedCrossRefGoogle Scholar
  57. 57.
    Artavanis-Tsakonas S, Simpson P. Choosing a cell fate: a view from the Notch locus. Trends Genet 1991; 7(11–12):403–408.PubMedGoogle Scholar
  58. 58.
    Kobayashi T, Terada Y, Kuwana H et al. Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury. Kidney Int 2008.Google Scholar
  59. 59.
    Gupta S, Li S, Abedin MJ et al. Effect of Notch activation on the regenerative response to acute renal failure. Am J Physiol Renal Physiol 2010; 298(1):F209–215.PubMedCrossRefGoogle Scholar
  60. 60.
    Niranjan T, Bielesz B, Gruenwald A et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med 2008; 14(3):290–298.PubMedCrossRefGoogle Scholar
  61. 61.
    Morrissey J, Guo G, Moridaira K et al. Transforming growth factor-beta induces renal epithelial jagged-1 expression in fibrotic disease. J Am Soc Nephrol 2002; 13(6):1499–1508.PubMedCrossRefGoogle Scholar
  62. 62.
    Waters AM, Wu MY, Onay T et al. Ectopic notch activation in developing podocytes causes glomerulosclerosis. J Am Soc Nephrol 2008; 19(6):1139–1157.PubMedCrossRefGoogle Scholar
  63. 63.
    Murea M, Park JK, Sharma S et al. Expression of Notch pathway proteins correlates with albuminuria, glomerulosclerosis and renal function. Kidney Int 2010.Google Scholar
  64. 64.
    Surendran K, Selassie M, Liapis H et al. Reduced Notch signaling leads to renal cysts and papillary microadenomas. J Am Soc Nephrol 2010; 21(5):819–832.PubMedCrossRefGoogle Scholar
  65. 65.
    Verdeguer F, Le Corre S, Fischer E et al. A mitotic transcriptional switch in polycystic kidney disease. Nat Med 2009.Google Scholar
  66. 66.
    Wang KL, Weinrach DM, Luan C et al. Renal papillary adenoma—a putative precursor of papillary renal cell carcinoma. Hum Pathol 2007; 38(2):239–246.PubMedCrossRefGoogle Scholar
  67. 67.
    Yang XJ, Tan MH, Kim HL et al. A molecular classification of papillary renal cell carcinoma. Cancer Res 2005; 65(13):5628–5637.PubMedCrossRefGoogle Scholar
  68. 68.
    Liang L, Zhang HW, Liang J et al. KyoT3, an isoform of murine FHL1, associates with the transcription factor RBP-J and represses the RBP-J-mediated transactivation. Biochim Biophys Acta 2008.Google Scholar
  69. 69.
    Sun S, Du R, Gao J et al. Expression and clinical significance of Notch receptors in human renal cell carcinoma. Pathology 2009; 41(4):335–341.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Hila Barak
    • 1
  • Kameswaran Surendran
    • 1
  • Scott C. Boyle
    • 1
  1. 1.Department of Developmental BiologyWashington University School of MedicineSt LouisUSA

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