TY - JOUR
T1 - Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud
AU - Zhao, Haotian
AU - Kegg, Heather
AU - Grady, Sandy
AU - Truong, Hoang Trang
AU - Robinson, Michael L.
AU - Baum, Michel
AU - Bates, Carlton M.
N1 - Funding Information:
We thank Dr. Fenglei Jiang for her contributions to the study and Cindy McAllister for her assistance with the confocal microscopy. We also thank Reena Shakya and Dr. Frank Costantini for the Hoxb7 promoter construct, Dr. Janet Rossant for the floxed fgfr1 mice, Dr. David Ornitz for the floxed fgfr2 mice, and Dr. Larry Patterson for the Foxd1 probe template. This study was supported by grants from the National Institute of Child Health and Human Development, 5 P30 HD34615-02 (C. M. B.), and the National Institute of Diabetes and Digestive and Kidney Disease, DK-41612 (M. B.).
PY - 2004/12/15
Y1 - 2004/12/15
N2 - 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, fgfr2UB-/- mice have very aberrant ureteric bud branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr2UB-/- ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced proliferation. The nephrogenic mesenchymal lineage in fgfr2UB-/- mice develops normal-appearing glomeruli and tubules, and only slightly fewer nephrons than controls. In contrast, fgfr2UB-/- kidneys have abnormally thickened subcapsular cortical stromal mesenchyme. Ultimately, fgfr2UB-/- adult kidneys are small and abnormally shaped or are hydronephrotic. Finally, there are no additional abnormalities in the fgfr1/2UB-/- kidneys versus the fgfr2UB-/- kidneys. In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning.
AB - 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, fgfr2UB-/- mice have very aberrant ureteric bud branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr2UB-/- ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced proliferation. The nephrogenic mesenchymal lineage in fgfr2UB-/- mice develops normal-appearing glomeruli and tubules, and only slightly fewer nephrons than controls. In contrast, fgfr2UB-/- kidneys have abnormally thickened subcapsular cortical stromal mesenchyme. Ultimately, fgfr2UB-/- adult kidneys are small and abnormally shaped or are hydronephrotic. Finally, there are no additional abnormalities in the fgfr1/2UB-/- kidneys versus the fgfr2UB-/- kidneys. In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning.
KW - Branching morphogenesis
KW - Conditional knockout
KW - Fibroblast growth factor receptors
KW - Kidney development
KW - Stromal patterning
KW - Ureteric bud
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U2 - 10.1016/j.ydbio.2004.09.002
DO - 10.1016/j.ydbio.2004.09.002
M3 - Article
C2 - 15581874
AN - SCOPUS:9944233235
SN - 0012-1606
VL - 276
SP - 403
EP - 415
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -