Deletion of Frs2[alpha] from the ureteric epithelium causes renal hypoplasia
Fibroblast growth factor receptor 2 (Fgfr2) signaling is critical in maintaining ureteric branching architecture and mesenchymal stromal morphogenesis in the kidney. Fibroblast growth factor receptor substrate 2α (Frs2α) is a major docking protein for Fgfr2 with downstream targets including Ets vari...
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Veröffentlicht in: | American journal of physiology. Renal physiology 2009-11, Vol.297 (5), p.F1208 |
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Sprache: | eng |
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Zusammenfassung: | Fibroblast growth factor receptor 2 (Fgfr2) signaling is critical in maintaining ureteric branching architecture and mesenchymal stromal morphogenesis in the kidney. Fibroblast growth factor receptor substrate 2α (Frs2α) is a major docking protein for Fgfr2 with downstream targets including Ets variant (Etv) 4 and Etv5 in other systems. Furthermore, global deletion of Frs2α causes early embryonic lethality. The purpose of the study was to determine the role of Frs2α in mediating Fgfr2 signaling in the ureteric epithelium. To that end, we generated mice with conditional deletion of Frs2α in the ureteric epithelium (Frs2α...) and mice with point mutations in the Frs2α binding site of Fgfr2 (Fgfr2...). Frs2α... mice developed mild renal hypoplasia characterized by decreased ureteric branching morphogenesis but maintained normal overall branching architecture and had normal mesenchymal stromal development. Reduced nephron endowment in postnatal mutant mice was observed, corresponding with the reduction in branching morphogenesis. Furthermore, there were no apparent renal abnormalities in Fgfr2... mice. Interestingly, Etv4 and Etv5 expression was unaltered in Frs2α... mice, as was Sprouty1, an antagonist of Frs2α signaling. However, Ret and Wnt11 (molecules critical for ureteric branching morphogenesis) mRNA levels were lower in mutants vs. controls. Taken together, these findings suggest that Fgfr2 signals through adapter molecules other than Frs2α in the ureteric epithelium. Furthermore, Frs2α may transmit signals through other receptor kinases present in ureteric epithelium. Finally, the renal hypoplasia observed in Frs2α... mice is likely secondary to decreased Ret and Wnt11 expression. (ProQuest: ... denotes formulae/symbols omitted.) |
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ISSN: | 1931-857X 1522-1466 |