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Three-Dimensional Imaging Reveals Ureteric and Mesenchymal Defects in Fgfr2-Mutant Kidneys

Sunder Sims-Lucas^*, Christos Argyropoulos, Kayle Kish, Kirk McHugh, John F. Bertram^||, Raymond Quigley^¶ and Carlton M. Bates^*,**

^* Rangos Research Center, Children’s Hospital of Pittsburgh of the University of Pennsylvania Medical Center, Pittsburgh, Pennsylvania;
Renal and Electrolyte Division, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;
Center for Cell and Developmental Biology, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio;
Division of Nephrology, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio;
^|| Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia;
^¶ Division of Nephrology, Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas;
^** Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Correspondence: Dr. Carlton M. Bates, Rangos Research Center, Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15201. Phone: 412-692-9442; Fax: 412-692-7756; E-mail: batescm{at}upmc.edu

Received for publication May 21, 2009. Accepted for publication August 20, 2009.

Current techniques to morphologically characterize the processes of nephrogenesis and ureteric branching during kidney development have many limitations. Here, we used in vivo three-dimensional analysis to study renal development in mice lacking fibroblast growth factor receptor 2 in the ureteric bud (Fgfr2^{UB−/−}) and in littermate controls. We found that Fgfr2^{UB−/−} mice have more severe defects in ureteric branching morphogenesis than previously reported, including significantly fewer branches and tips than control mice. Furthermore, these mice had decreased ureteric volume and surface area and longer ureteric segments than control mice. We also observed previously unrecognized abnormalities in nephrogenesis, including a gradual increase in volume and surface area during maturation from renal vesicles to mature nephrons, in the mutant mice. Finally, we quantified many events of normal renal development that are either difficult or impossible to measure without this three-dimensional technique. In summary, the three-dimensional approach is a powerful and quantitative means to characterize branching morphogenesis and nephrogenesis.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673