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

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.