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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.12.034 Byline: Deepali Pitre Poladia (a), Kayle Kish (a), Benjamin Kutay (a), David Hains (a), Heather Kegg (a), Haotian Zhao (b), Carlton M. Bates (a)(c) Keywords: Fibroblast growth factor receptor; Kidney development; Metanephric mesenchyme; Pax3 promoter; Conditional knockout Abstract: To determine the importance of fibroblast growth factor receptors (fgfrs) 1 and 2 in the metanephric mesenchyme, we generated conditional knockout mice (fgfr.sup.Mes-/-).Fgfr1.sup.Mes-/- andfgfr2.sup.Mes-/- mice develop normal-appearing kidneys. Deletion of both receptors (fgfr1/2.sup.Mes-/-) results in renal aplasia.Fgfr1/2.sup.Mes-/- mice develop a ureteric bud (and occasionally an ectopic bud) that does not elongate or branch, and the mice do not develop an obvious metanephric mesenchyme. By in situ hybridization, regions of mutant mesenchyme near the ureteric bud(s) expressEya1 andSix1, but notSix2,Sall1, orPax2, while the ureteric bud expressesRet andPax2 normally. Abnormally high rates of apoptosis and relatively low rates of proliferation are present in mutant mesenchyme dorsal to the mutant ureteric bud at embryonic day (E) 10.5, while mutant ureteric bud tissues undergo high rates of apoptosis by E11.5. Thus,fgfr1 andfgfr2 together are critical for normal formation of metanephric mesenchyme. While the ureteric bud(s) initiates, it does not elongate or branch infgfr1/2.sup.Mes-/- mice. In metanephric mesenchymal rudiments,fgfr1 andfgfr2 appear to function downstream ofEya1 andSix1, but upstream ofSix2,Sall1, andPax2. Finally, this is the first example of renal aplasia in a conditional knockout model. Author Affiliation: (a) Center for Cell and Vascular Biology, Columbus Children's Research Institute, 700 Children's Drive, Columbus, OH 43205, USA (b) St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA (c) Division of Nephrology, Department of Pediatrics, The Ohio State University College of Medicine and Public Health, 370 W. 9th Avenue, Columbus, OH 43210, USA Article History: Received 24 June 2005; Revised 21 November 2005; Accepted 16 December 2005

A study on the impact of fibroblast growth factor receptors 1 and 2 in kidney development in embryos of mice is presented.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2004.09.002 Byline: Haotian Zhao (a), Heather Kegg (a), Sandy Grady (a), Hoang-Trang Truong (b), Michael L. Robinson (a), Michel Baum (b), Carlton M. Bates (a)(c) Keywords: Fibroblast growth factor receptors; Kidney development; Ureteric bud; Branching morphogenesis; Stromal patterning; Conditional knockout 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.sup.UB-/-) results in no apparent renal abnormalities. In contrast, fgfr2.sup.UB-/- mice have very aberrant ureteric bud branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr2.sup.UB-/- ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced proliferation. The nephrogenic mesenchymal lineage in fgfr2.sup.UB-/- mice develops normal-appearing glomeruli and tubules, and only slightly fewer nephrons than controls. In contrast, fgfr2.sup.UB-/- kidneys have abnormally thickened subcapsular cortical stromal mesenchyme. Ultimately, fgfr2.sup.UB-/- adult kidneys are small and abnormally shaped or are hydronephrotic. Finally, there are no additional abnormalities in the fgfr1/2.sup.UB-/- kidneys versus the fgfr2.sup.UB-/- kidneys. In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning. Author Affiliation: (a) Center for Human and Molecular Genetics, Columbus Children's Research Institute, Columbus, OH 43205, United States (b) Department of Pediatrics, Division of Nephrology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235, United States (c) Department of Pediatrics, Division of Nephrology, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, United States Article History: Received 18 May 2004; Revised 20 August 2004; Accepted 1 September 2004

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 (fgfr[1.sup.UB-/-]) results in no apparent renal abnormalities. In contrast, fgfr[2.sup.UB-/-] mice have very aberrant ureteric bud branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr[2.sup.UB-/-] ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced proliferation. The nephrogenic mesenchymal lineage in fgfr[2.sup.UB-/-] mice develops normal-appearing glomeruli and tubules, and only slightly fewer nephrons than controls. In contrast, fgfr[2.sup.UB-/-] kidneys have abnormally thickened subcapsular cortical stromal mesenchyme. Ultimately, fgfr[2.sup.UB-/-] adult kidneys are small and abnormally shaped or are hydronephrotic. Finally, there are no additional abnormalities in the fgfr[1/2.sup.UB-/-] kidneys versus the fgfr[2.sup.UB-/-] kidneys. In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning. Keywords: Fibroblast growth factor receptors; Kidney development; Uretcric bud; Branching morphogenesis; Stromal patterning; Conditional knockout