Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud

Haotian Zhao1, Heather Kegg, Sandy Grady

  • 1Center for Human and Molecular Genetics, Columbus Children's Research Institute, 700 Children's Drive, Columbus, OH 43205, USA.

Developmental Biology
|December 8, 2004
PubMed

Insights

Fibroblast Growth Factor Receptor 2 (FGFR2) is essential for kidney development, specifically ureteric bud branching. FGFR1 is not critical for this process.

Area of Science:

  • Developmental biology
  • Molecular biology
  • Genetics

Background:

  • Fibroblast Growth Factor Receptors (FGFRs) are vital signaling proteins.
  • FGFR1 and FGFR2 gene deletions are embryonic lethal before kidney development.

Purpose of the Study:

  • To investigate the specific roles of FGFR1 and FGFR2 in ureteric bud development using conditional gene targeting.
  • To elucidate the function of FGFRs in kidney morphogenesis.

Main Methods:

  • Generated transgenic mice with Hoxb7 promoter-driven cre recombinase for ureteric bud-specific gene deletion.
  • Utilized conditional targeting to create fgfr1(UB-/-), fgfr2(UB-/-), and fgfr1/2(UB-/-) mouse models.
  • Analyzed kidney development, ureteric bud branching, cell proliferation, apoptosis, and stromal mesenchyme patterning.

Main Results:

  • fgfr1 deletion in the ureteric bud (fgfr1(UB-/-)) showed no renal abnormalities.
  • fgfr2 deletion (fgfr2(UB-/-)) led to aberrant ureteric bud branching, reduced proliferation, and increased apoptosis in ureteric bud tips.
  • fgfr2(UB-/-) kidneys exhibited abnormal stromal mesenchyme, resulting in small, misshapen, or hydronephrotic adult kidneys. No additional defects were observed in fgfr1/2(UB-/-) kidneys compared to fgfr2(UB-/-).

Conclusions:

  • FGFR2 plays a critical role in ureteric bud branching morphogenesis and kidney development.
  • FGFR1 does not appear to be essential for ureteric bud branching or kidney development.
  • FGFR2 is crucial for patterning the kidney's stromal mesenchyme.

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