Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud.
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.
Zhao
Haotian
H
Center for Human and Molecular Genetics, Columbus Children's Research Institute, 700 Children's Drive, Columbus, OH 43205, USA.
Kegg
Heather
H
Grady
Sandy
S
Truong
Hoang-Trang
HT
Robinson
Michael L
ML
Baum
Michel
M
Bates
Carlton M
CM
D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D004628:Embryonic Structures / Q000033:anatomy & histology / Q000378:metabolism; D018390:Gene Targeting; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D007668:Kidney / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014513:Ureter / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism
D018398:Homeodomain Proteins; C093253:Hoxb7 protein, mouse; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2