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Updated: Aug 20, 2026

Dissection and Culture of Mouse Embryonic Kidney
Published on: May 17, 2017
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.
Abstract:
Fibroblast growth receptors (FGFRs) consist of four signaling family members. Mice with deletions of fgfr1 or fgfr2 are embryonic lethal prior to the onset of kidney development. To determine roles of FGFR1 and FGFR2 in the ureteric bud, we used a conditional targeting approach. First, we generated transgenic mice using the Hoxb7 promoter to drive cre recombinase and green fluorescent protein expression throughout ureteric bud tissue. We crossed Hoxb7creEGFP mice with mice carrying lox-p sites flanking critical regions of fgfr1 and/or fgfr2. Absence of fgfr1 from the ureteric bud (fgfr1(UB-/-)) results in no apparent renal abnormalities. In contrast, fgfr2(UB-/-) mice have very aberrant ureteric bud branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr2(UB-/-) ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced proliferation. The nephrogenic mesenchymal lineage in fgfr2(UB-/-) mice develops normal-appearing glomeruli and tubules, and only slightly fewer nephrons than controls. In contrast, fgfr2(UB-/-) kidneys have abnormally thickened subcapsular cortical stromal mesenchyme. Ultimately, fgfr2(UB-/-) adult kidneys are small and abnormally shaped or are hydronephrotic. Finally, there are no additional abnormalities in the fgfr1/2(UB-/-) kidneys versus the fgfr2(UB-/-) kidneys. In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning.
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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