Renin-angiotensin system-growth factor cross-talk: a novel mechanism for ureteric bud morphogenesis

Pediatr Nephrol. 2009 Jun;24(6):1113-20. doi: 10.1007/s00467-008-1021-9. Epub 2008 Oct 29.


The renin-angiotensin system (RAS) plays a critical role in kidney development. Mutations in the genes encoding components of the RAS cause a spectrum of congenital abnormalities of the kidney and renal collecting system, ranging from hypoplasia of the renal medulla and hydronephrosis in mice to renal tubular dysgenesis in humans. However, the mechanisms by which an intact RAS controls proper renal system development and how aberrations in the RAS result in abnormal kidney and renal collecting system development are poorly understood. The renal collecting system originates from the ureteric bud (UB). A number of transcription and growth factors regulate UB branching morphogenesis to ultimately form the ureter, pelvis, calyces, medullary, and cortical collecting ducts. Importantly, UB morphogenesis is a key developmental process that controls organogenesis of the entire metanephros. This review emphasizes emerging insights into the role for the RAS in UB morphogenesis and explores the mechanisms whereby RAS regulates this important process. A conceptual framework derived from recent work indicates that cooperation between the angiotensin II AT(1) receptor and receptor tyrosine kinase signaling performs essential functions during renal collecting system development via control of UB branching morphogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Embryonic Development / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Developmental
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Humans
  • Kidney / metabolism
  • Morphogenesis / genetics*
  • Proto-Oncogene Proteins c-ret / metabolism
  • Renin-Angiotensin System / physiology*
  • Ureter / physiology*


  • Glial Cell Line-Derived Neurotrophic Factor
  • ErbB Receptors
  • Proto-Oncogene Proteins c-ret