Skip to main content
SpringerLink
Log in

Molecular biology of ureteral bud and trigonal development

  • Published:
Current Urology Reports Aims and scope Submit manuscript

Abstract

Advances in molecular biology have provided valuable insight into the development of the urinary tract, particularly ureteral bud formation. Reciprocal inductive signals between the ureteral bud and growing kidney are crucial for normal development. The Wolffian duct serves as the site of origin of the ureteral bud and forms distal excretory ducts that are incorporated into the developing bladder to become the trigone. Vesicoureteral reflux and renal dysplasia can result from abnormal position of the ureteral orifice on the trigone. The presumed origin of trigone formation is based largely on evaluation of human and animal models performed nearly a century ago. The trigone is thought to develop from the mesodermal germ cell layer; however, several recent studies have shown that endoderm may be the tissue of origin. This review highlights important discoveries in the field of molecular biology as it relates to the development of normal and abnormal ureteral bud formation. It also describes the anatomic relationship between the developing bud and trigone as it pertains to clinically relevant urinary tract anomalies, including recent discoveries that attempt to prove the origin of the trigone.

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. Glassberg K: Normal and abnormal development of the kidney: a clinician’s interpretation of current knowledge. J Urol 2002, 167:2339–2351. This is a comprehensive review of molecular kidney development that a clinician can understand. It should serve as a cornerstone of reference for anyone looking for an overview of this topic.

    Article  PubMed  CAS  Google Scholar 

  3. Davies JA, Brandli AW: The Kidney Development Database. www.ana.ed.ac.uk/anatomy/database/kidbase/kidhome.html. Accessed August 18, 2004.

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

    PubMed  CAS  Google Scholar 

  5. Pohl M, Bhatnagar V, Mendoza SA, Nigam SK: Toward an etiological classification of developmental disorders of the kidney and upper urinary tract. Kidney Int 2002, 61:10–19.

    Article  PubMed  Google Scholar 

  6. Lechner MS, Dressler GR: The molecular basis of embryonic kidney development. Mech Develop 1997, 62:105–120.

    Article  CAS  Google Scholar 

  7. Sakurai H: Molecular mechanisms of ureteric bud development. Semin Cell Dev Biol 2003, 14:217–224.

    Article  PubMed  CAS  Google Scholar 

  8. Schuchardt A, D’Agati V, Pachnis V, Costantini F: 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 

  9. Schedl A, Hastie ND: Cross-talk in kidney development. Curr Opin Genet Dev 2000, 10:543–549.

    Article  PubMed  CAS  Google Scholar 

  10. 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 

  11. 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 

  12. Pope JC IV, Brock JW III, Adams MC, et al.: How they begin and how they end: classic and new theories for the development and deterioration of congenital anomalies of the kidney and urinary tract (CAKUT). J Am Soc Nephrol 1999, 10:2018–2029. This paper reviews a historic as well as a new theory explaining congenital anomalies of the kidney and urinary tract. It provides experimental data that provide a potential explanation for anomalies that are seen clinically.

    PubMed  Google Scholar 

  13. Miyamoto N, Yoshida M, Kuratani S, et al.: Defects of urogenital development in mice lacking Emx2. Development 1997, 124:1653–1664.

    PubMed  CAS  Google Scholar 

  14. Majumdar A, Vainio S, Kispert A, et al.: Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 2003, 130:3175–3185.

    Article  PubMed  CAS  Google Scholar 

  15. Bush KT, Sakurai H, Steer DL, et al.: TGF-_ superfamily members modulate growth, branching, shaping, and patterning of the ureteric bud. Dev Biol 2004, 266:285–298.

    Article  PubMed  CAS  Google Scholar 

  16. Miyazaki Y, Oshima K, Fogo A, et al.: 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 

  17. Mackie GG, Stephens FD: Duplex kidneys: a correlation of renal dysplasia with position of the ureteral orifice. J Urol 1975, 114:274–280.

    PubMed  CAS  Google Scholar 

  18. Park JM: Normal and anomalous development of the urogenital system. In Campbell’s Urology, edn 8. Edited by Walsh PC, Retik AB, Vaughn ED, Wein AJ. Philadelphia: Saunders; 2002:1737–1753.

    Google Scholar 

  19. Kakuchi J, Ichiki T, Kiyama S, et al.: Developmental expression of renal angiotensin II receptor genes in the mouse. Kidney Int 1995, 47:140–147.

    Article  PubMed  CAS  Google Scholar 

  20. Stoneking BJ, Hunley TE, Nishimura H, et al.: Renal angiotensin converting enzyme promotes renal damage during ureteral obstruction. J Urol 1998, 160:1070–1074.

    Article  PubMed  CAS  Google Scholar 

  21. 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, 165:196–202.

    Article  PubMed  CAS  Google Scholar 

  22. Oshima K, Miyazaki Y, Brock JW III, et al.: Angiotensin type-II receptor expression and ureteral budding. J Urol 2001, 166:1848–1852.

    Article  PubMed  CAS  Google Scholar 

  23. Nishimura H, Yerkes E, Hohenfellner K, et al.: Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. Mol Cell 1999, 3:1–10.

    Article  PubMed  CAS  Google Scholar 

  24. Sadler TW: Langman’s Medical Embryology. Philadelphia: Lippincott Williams & Wilkins; 2000.

    Google Scholar 

  25. Keibel F: Zur entwicklungsgeschichte d. menshlichen, urogenital-apparates. Arch F Anat U Entw Anat Abt 1896, 55:157.

    Google Scholar 

  26. Felix W: The development of the urogenital organs. In Manual of Human Embryology, vol 2. Philadelphia and London: Keibel-Mall; 1912:752.

    Google Scholar 

  27. Chwalla R: Entwickling der Harnblase u.d. primitiven Harnrohre. Anat Entwicklungsgesch 1927, 83:615.

    Article  Google Scholar 

  28. Sprenkle PC, Batourina E, Tsai S, et al.: The bladder trigone is not a Wolffian duct remnant. Presented at the American Urological Association Annual Meeting. San Francisco: May 8–13, 2004.

  29. Baskin LS, Hayward SW, Young P, et al.: Role of mesenchymalepithelial interactions in normal bladder development. J Urol 1996, 156:1820–1827.

    Article  PubMed  CAS  Google Scholar 

  30. Hayward SW: Approaches to modeling stromal-epithelial interactions. J Urol 2002, 168:1165–1172. Tissue recombination experiments are an excellent way to study stromalepithelial signaling in vivo. This paper provides an overview of stromalepithelial interactions while highlighting technologic advances using transgenic or knock-out mice.

    Article  PubMed  Google Scholar 

  31. Cunha GR, Hayashi N, Wong YC: Regulation of differentiation and growth of normal adult and neoplastic epithelia by inductive mesenchyme. Cancer Surv 1991, 11:73–90.

    PubMed  CAS  Google Scholar 

  32. DeMarco RT, Ishii K, Pope JC IV, et al.: The use of stromal-epithelial interactions in examining trigonal formation: Is classic embryology teaching correct? Presented at the American Urological Association Annual Meeting. San Francisco: May 8–13, 2004.

  33. Rush WH, Currie DP: Hemitrigone: renal agenesis or single ureteral ectopia. Urology 1978, 11:161–163.

    Article  PubMed  Google Scholar 

  34. Tanagho EA, Meyers FH, Smith DR: The trigone: anatomical and physiological considerations. 1: In relation to the ureterovesical junction. J Urol 1968, 100:623–632.

    PubMed  CAS  Google Scholar 

  35. Tanagho EA, Hutch JA, Meyers FH, Rambo ON Jr: Primary vesicoureteral reflux: experimental studies of its etiology. J Urol 1965, 93:165–176.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urologic Surgery, Division of Pediatric Urology, Vanderbilt Children’s Hospital, 435 Medical Arts Building, 1211 21st Avenue South, 37212-2721, Nashville, TN, USA

    John C. Pope MD

Authors
  1. John C. Thomas MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Romano T. DeMarco MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John C. Pope 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

Thomas, J.C., DeMarco, R.T. & Pope, J.C. Molecular biology of ureteral bud and trigonal development. Curr Urol Rep 6, 146–151 (2005). https://doi.org/10.1007/s11934-005-0084-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11934-005-0084-4

Keywords

Search

Navigation