期刊
DEVELOPMENTAL BIOLOGY
卷 276, 期 2, 页码 403-415出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2004.09.002
关键词
fibroblast growth factor receptors; kidney development; ureteric bud; branching morphogenesis; stromal patterning; conditional knockout
资金
- NICHD NIH HHS [5 P30 HD34615-02] Funding Source: Medline
- NIDDK NIH HHS [R01 DK041612, DK-41612] Funding Source: Medline
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 ere 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 fg/r2(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 7 there are no additional abnormalities in the fgfr1/2(UB-/-) kidneys versus the fgfr(UB-/-) kidneys. In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning. (C) 2004 Elsevier Inc. All rights reserved.
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