Fibroblast growth factor receptor signaling in kidney and lower urinary tract development

Pediatr Nephrol. 2016 Jun;31(6):885-95. doi: 10.1007/s00467-015-3151-1. Epub 2015 Aug 21.

Abstract

Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together, these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans.

Keywords: Bladder organogenesis; Conditional knockout; Fibroblast growth factors; Metanephric mesenchyme; Renal organogenesis; Ureteric bud.

Publication types

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

MeSH terms

  • Acanthosis Nigricans / genetics
  • Acanthosis Nigricans / metabolism
  • Acrocephalosyndactylia / genetics
  • Acrocephalosyndactylia / metabolism
  • Animals
  • Antley-Bixler Syndrome Phenotype / genetics
  • Antley-Bixler Syndrome Phenotype / metabolism
  • Apoptosis
  • Craniosynostoses / genetics
  • Craniosynostoses / metabolism
  • Ear / abnormalities
  • Fibroblast Growth Factors / metabolism*
  • Gene Knockout Techniques / methods
  • Humans
  • Kidney / growth & development*
  • Kidney / metabolism
  • Kidney / pathology
  • Mice
  • Models, Animal
  • Mutation
  • Organogenesis* / genetics
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / metabolism*
  • Scalp Dermatoses / genetics
  • Scalp Dermatoses / metabolism
  • Signal Transduction
  • Skin Abnormalities / genetics
  • Skin Abnormalities / metabolism
  • T-Box Domain Proteins / genetics
  • Ureter / growth & development*
  • Ureter / metabolism
  • Ureter / pathology
  • Urinary Bladder / growth & development*
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Wolffian Ducts / growth & development*
  • Wolffian Ducts / metabolism

Substances

  • Receptors, Fibroblast Growth Factor
  • T-Box Domain Proteins
  • Tbx18 protein, mouse
  • Fibroblast Growth Factors

Supplementary concepts

  • Cutis Gyrata Syndrome of Beare And Stevenson