1. Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme
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Poladia, Deepali Pitre, Kish, Kayle, Kutay, Benjamin, Hains, David, Kegg, Heather, Zhao, Haotian, and Bates, Carlton M.
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Stem cells -- Analysis ,Fibroblast growth factors -- Analysis ,Biological sciences - Abstract
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
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- 2006