Role of fibroblast growth factor receptor signaling in kidney development

Carlton M Bates1

  • 1Rangos Research Center, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA. batescm@upmc.edu

Insights

Fibroblast growth factor receptors (Fgfrs) are crucial for kidney development. Their signaling pathways regulate the formation and patterning of virtually all renal lineages throughout kidney development.

Area of Science:

  • Developmental Biology
  • Renal Physiology
  • Molecular Biology

Background:

  • Fibroblast growth factor receptors (Fgfrs) are present in the developing kidney.
  • Exogenous fibroblast growth factors (Fgfs) influence metanephric mesenchyme (MM) and ureteric bud (UB) growth and maturation.
  • Previous studies highlight the significance of Fgfr signaling in renal development.

Purpose of the Study:

  • To investigate the critical role of Fgfr signaling in kidney development.
  • To elucidate the specific contributions of Fgfrs and Fgfs to renal lineage patterning.

Main Methods:

  • Analysis of transgenic mice over-expressing dominant-negative Fgfr isoforms.
  • Gene deletion studies (global and conditional) targeting Fgf7, Fgf10, Fgfr2IIIb, Fgfrl1, Fgf8, Fgfr2, and Frs2α.
  • Examination of renal development, including renal aplasia, dysplasia, hypoplasia, and ureteric branching defects.

Main Results:

  • Over-expression of dominant-negative Fgfrs leads to renal aplasia/severe dysplasia.
  • Deletion of Fgf7, Fgf10, and Fgfr2IIIb results in smaller kidneys with reduced collecting ducts and nephrons.
  • Loss of Fgfrl1 causes severe renal dysgenesis; Fgf8 deletion from MM interrupts nephron formation.
  • Fgfr2 deletion in UB causes severe ureteric branching defects; Frs2α loss in UB leads to mild hypoplasia.
  • Combined Fgfr1/Fgfr2 deletion in MM results in renal aplasia and impaired MM/UB development.
  • Fgfr2 loss in MM causes renal and urinary tract anomalies, including vesicoureteral reflux.

Conclusions:

  • Fgfr signaling is essential for the patterning of all renal lineages during kidney development.
  • Disruptions in Fgfr signaling lead to a spectrum of renal developmental abnormalities.
  • Fgfrs play critical roles at both early and late stages of kidney formation.

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