Skip to main content
SpringerLink
Log in

Molecular genetics of renal development

  • Published:
Current Urology Reports Aims and scope Submit manuscript

Abstract

The understanding of the complex branching morphogenesis of the early kidney is at an early stage; however, a framework is emerging that suggests numerous active genes sequentially switching on and reciprocally influencing each other. Much of our understanding of this process comes from studies of rodents specifically engineered to lack a particular gene responsible for an inductive agent or receptor. This review attempts to place newly discovered genetic programs within an organized framework of sequential renal development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Grobstein C: Inductive epithelio-mesenchymal interaction in cultured organ rudiments of the mouse. Science 1953, 118:52–55.

    Article  PubMed  CAS  Google Scholar 

  2. Orellana SA, Avner ED: Cell and molecular biology of kidney development. Semin Nephrol 1998, 18:233–243.

    PubMed  CAS  Google Scholar 

  3. Armstrong J F, Pritchard-Jones K, Bickmore WA, et al.: The expression of the Wilms’ tumour gene, WT1, in the developing mammalian embryo. Mech Dev 1992, 40:85–97.

    Article  Google Scholar 

  4. Sainio K, Suvanto P, Davies J, et al.: Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium. Development 1997,124:4077–4087.

    PubMed  CAS  Google Scholar 

  5. Xu PX, Adams J, Peters H, et al.: Eyal-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet 1999, 23:113–117.

    Article  PubMed  CAS  Google Scholar 

  6. Burrow C: Retinoids and Renal Development. Exp Nephrol. 2000, 8:219–225. Very comprehensive and detail-oriented summary of the known retinoid effects on renal development.

    Article  PubMed  CAS  Google Scholar 

  7. Wilson JG, Roth CB, Warkany J: An analysis of the syndrome of malformations induced by maternal vitamin A deficiency: effects of restoration of vitamin A at various times during gestation. Am J Anat 1953, 92:189–217.

    Article  PubMed  CAS  Google Scholar 

  8. Mendelsohn C, Batourina E, Fung S, et al.: Stromal cells mediate retinoid dependent functions essential for renal development. Development 1999, 126:1139–1148.

    PubMed  CAS  Google Scholar 

  9. Pope JC IV, Brock JW III, Adams MC, et al.: Congenital anomalies of the kidney and urinary tract-role of the loss of function mutation in the pluripotent angiotensin type 2 receptor gene. J Urol 2001, 165:196.

    Article  PubMed  CAS  Google Scholar 

  10. Burrow C: Regulatory molecules in kidney development. Pediatr Nephrol 2000, 14:240–253. Detailed, precise, and dense overview of the current understanding of molecular control in renal development.

    Article  PubMed  CAS  Google Scholar 

  11. Lu HC, Revelli JP, Goering L, et al.: Retinoid signaling is required for the establishment of a ZPA and for the expression of Hoxb-8, a mediator of ZPA formation. Development 1997, 124:1643–1651.

    PubMed  CAS  Google Scholar 

  12. Weller A, Sorokin L, Illgen EM, Ekblom P: Development and growth of mouse embryonic kidney in organ culture and modulation of development by soluble growth factor. Dev Biol 1991, 144:248–261.

    Article  PubMed  CAS  Google Scholar 

  13. Glassberg K: Normal and abnormal development of the kidney: a clinician’s interpretation of current knowledge. J Urol 2002, 167:2339–2351. This is an outstanding review of renal development. It defines and integrates genetic control of development. Mandatory reading for clinicians wanting a comprehensive overview of recent advances.

    Article  PubMed  CAS  Google Scholar 

  14. Grobstein C: Morphogenetic interaction between embryonic mouse tissue separated by a membrane filter. Nature 1953, 172:869.

    Article  PubMed  CAS  Google Scholar 

  15. Burrow CR, Wilson PD: A putative Wilms’ tumor secreted growth factor activity required for primary culture of human nephroblasts. Proc Natl Acad Sci U S A 1993, 90:6066–6070.

    Article  PubMed  CAS  Google Scholar 

  16. Drummond IA, Mukhopadhyay D, Sukhatme VP: Expression of fetal kidney growth factors in a kidney tumor line: role of FGF2 in kidney development. Exp Nephrol 1998, 6:522–533.

    Article  PubMed  CAS  Google Scholar 

  17. Barasch J, Yang J, Qiao J, et al.: 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.

    PubMed  CAS  Google Scholar 

  18. Stuart RO, Nigam SK: Developmental biology of the kidney. In The Kidney. Edited by Brenner BM. Philadelphia: WB Saunders; 1999.

    Google Scholar 

  19. Qiao J, Sakurai H, Nigam SK: Branching morphogenesis independent of mesenchymal-epithelial contact in the developing kidney. Proc Natl Acad Sci U S A 1999, 96:7330–7335.

    Article  PubMed  CAS  Google Scholar 

  20. Pavlova A, Stuart RO, Pohl M, Nigam SK: Evolution of gene expression patterns in a model of branching morphogenesis. Am J Physiol 1999, 277:F650-F663.

    PubMed  CAS  Google Scholar 

  21. George SE, Simokat K, Hardin J, Chisholm AD: The VAB-1 Eph receptor tyrosine kinase functions in neural and epithelial morphogenesis in C. elegans. Cell 1998, 92:633–643.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Schmidt C, Bladt F, Goedecke S, et al.: Scatter factor/hepatocyte growth factor is essential for liver development. Nature 1995, 373:699–702.

    Article  PubMed  CAS  Google Scholar 

  24. Miyamoto N, Yoshida M, Kuratani S, et al.: Defects of urogenital development in mice lacking EMX2. Development 1997, 124:1653–1654.

    PubMed  CAS  Google Scholar 

  25. 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 

  26. 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 

  27. Ekblom P, Ekblom M, Fecker L, et al.: Role of mesenchymal nidogen for epithelial morphogenesis in vitro. Development 1994, 120:2003–2014.

    PubMed  CAS  Google Scholar 

  28. Lelongt B, Trugnan G, Murphy G, Ronco PM: Matrix metalloproteinases MMP2 and MMP9 are produced in early stages of kidney morphogenesis but only MMP9 is required for renal organogenesis in vitro. J Cell Biol 1997, 136:1363–1373.

    Article  PubMed  CAS  Google Scholar 

  29. Santos OF, 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 

  30. Sakurai H, Nigam SK: Transforming growth factor-β selectively inhibits branching morphogenesis but not tubulogenesis. Am J Physiol 1997, 272:F139-F146.

    PubMed  CAS  Google Scholar 

  31. Zhao J, Sime PJ, Bringas P Jr, et al.: Epithelium-specific adenoviral transfer of a dominantnegative mutant TGF-β type II receptor stimulates embryonic lung branching morphogenesis in culture and potentiates EGF and PDGF-AA. Mech Dev 1998, 72:89–100.

    Article  PubMed  CAS  Google Scholar 

  32. Sakurai H, Nigam SK: In vitro branching tubulogenesis: implications for developmental and cystic disorders, nephron number, renal repair, and nephron engineering. Kidney Int 1998, 54:14–26.

    Article  PubMed  CAS  Google Scholar 

  33. Sakurai H, Tsukamoto T, Kjelsberg CA, et al.: EGF receptor ligands are a large fraction of in vitro branching morphogens secreted by embryonic kidney. Am J Physiol 1997, 273:F463-F472.

    PubMed  CAS  Google Scholar 

  34. Barasch J, Yang J, Qiao J, et al.: 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 

  35. Davis AP, Witte DP, Hsieh-Li HM, et al.: Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature 1995, 375:791–795.

    Article  PubMed  CAS  Google Scholar 

  36. Braunhut SJ, Moses MA: Retinoids modulate endothelial cell production of matrix-degrading proteases and tissue inhibitors of metalloproteinases (TIMP). J Biol Chem 1994, 269:13472–13479.

    PubMed  CAS  Google Scholar 

  37. Kim E, Amould T, Walz G: Isolation of polycystin-interacting proteins. J Am Soc Nephrol 1997, 8:357A.

    Google Scholar 

  38. Lu W, Peissel B, Babakhanlou H, et al.: Perinatal lethality with kidney and pancreas defects in mice with a targeted Pkd1 mutation. Nat Genet 1997, 17:179–181.

    Article  PubMed  CAS  Google Scholar 

  39. Arnould T, Kim E, Tsiokas L: et al.: The polycystic kidney disease 1 gene product mediates protein kinase C alpha-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1. J Biol Chem 1998, 273:6013–6018.

    Article  PubMed  CAS  Google Scholar 

  40. Wilson PD, Geng L, Li X, Burrow CR: The PKD1 gene product, “Polycystin-1,” is a tyrosine-phosphorylated protein that colocalizes with alpha2beta1 integrin in focal clusters in adherent renal epithelia. Lab Invest 1999, 79:1311–1323. Clear, precisely written exposition of PKD1 gene expression, which is a subject of intrinsic importance and a model for other renal genetic control pathways.

    PubMed  CAS  Google Scholar 

  41. Du J, Wilson PD: Abnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD. Am J Physiol 1995, 269:C487-C495.

    PubMed  CAS  Google Scholar 

  42. Mochizuki T, Wu G, Hayashi T, et al.: PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 1996, 272:1339–1342.

    Article  PubMed  CAS  Google Scholar 

  43. Donovan M, Natoli T, Sainio K, et al.: Initial differentiation of the metanephric mesenchyme is independent of WT1 and the ureteric bud. Dev Genet 1999, 24:252–262. A sharp analysis of early differentiation, an area of much interest and controversy.

    Article  PubMed  CAS  Google Scholar 

  44. 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 

  45. Torres M, Gomez-Pardo E, Dressler GR, Gruss P: Pax-2 controls multiple steps of urogenital development. Development 1995, 121:4057–4065.

    PubMed  CAS  Google Scholar 

  46. Yang Y, Jeanpierre C, Dressler GR, et al.: WT1 and PAX-2 podocyte expression in Denys-Drash syndrome and isolated diffuse mesangial sclerosis. Am J Pathol 1999, 154:181–192.

    PubMed  CAS  Google Scholar 

  47. Tufro A: VEGF spatially directs angiogenesis during metanephric development in vitro. Dev Biol 2000, 227:558–566.

    Article  PubMed  CAS  Google Scholar 

  48. Guron G, Friberg P: An intact renin-angiotensin system is a prerequisite for normal renal development. J Hypertens 2000, 18:123–137.

    Article  PubMed  CAS  Google Scholar 

  49. Brock JW, III, Hunley TE, Adams MC, Kon V: Role of the renin-angiotensin system in disorders of the urinary tract. J Urol 1998, 160:1812–1819.

    Article  PubMed  CAS  Google Scholar 

  50. Buttar H: An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. Mol Cell Biochem 1997, 176:61–71.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric Urology, Mount Sinai School of Medicine, 5 E. 98th Street, Box 1272, 10029, New York, NY, USA

    Michael E. Levin MD & Richard N. Schlussel MD

Authors
  1. Michael E. Levin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard N. Schlussel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Michael E., L., Richard N., S. Molecular genetics of renal development. Curr Urol Rep 4, 171–176 (2003). https://doi.org/10.1007/s11934-003-0046-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11934-003-0046-7

Keywords

Search

Navigation