ArticleAmerican journal of physiology. Renal physiology2009
Deletion of Frs2alpha from the ureteric epithelium causes renal hypoplasia.
Article in American journal of physiology. Renal physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- FGF signaling regulates development by processes beyond canonical pathways.Genes & development · 2020Article
- In utero exposure to maternal diabetes impairs nephron progenitor differentiation.American journal of physiology. Renal physiology · 2019Article
- Regulation of Renal Differentiation by Trophic Factors.Frontiers in physiology · 2018Review
- Fgfr2 is integral for bladder mesenchyme patterning and function.American journal of physiology. Renal physiology · 2017Article
- Fibroblast growth factor receptor signaling in kidney and lower urinary tract development.Pediatric nephrology (Berlin, Germany) · 2016Review
- Genetic insights into the mechanisms of Fgf signaling.Genes & development · 2016Review
- Developmental Genetics and Congenital Anomalies of the Kidney and Urinary Tract.Journal of pediatric genetics · 2016Review
- Fgfr2 is integral for bladder mesenchyme patterning and function.American journal of physiology. Renal physiology · 2015Article
- Fibroblast growth factor receptor-Frs2α signaling is critical for nephron progenitors.Developmental biology · 2015Article
- To bud or not to bud: the RET perspective in CAKUT.Pediatric nephrology (Berlin, Germany) · 2014Review
- Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning.PloS one · 2014Article
- The Role of fibroblast growth factor receptor substrate 2 (FRS2) in the regulation of two activity levels of the components of the extracellular signal-regulated kinase (ERK) pathway in the mouse epididymis.Biology of reproduction · 2013Article
- Role of FGFRL1 and other FGF signaling proteins in early kidney development.Cellular and molecular life sciences : CMLS · 2013Review
- Article
- Ureteric morphogenesis requires Fgfr1 and Fgfr2/Frs2α signaling in the metanephric mesenchyme.Journal of the American Society of Nephrology : JASN · 2012Article
- Genes in the ureteric budding pathway: association study on vesico-ureteral reflux patients.PloS one · 2012Article
- Role of fibroblast growth factor receptor signaling in kidney development.Pediatric nephrology (Berlin, Germany) · 2011Review
- Renin-angiotensin system in ureteric bud branching morphogenesis: insights into the mechanisms.Pediatric nephrology (Berlin, Germany) · 2011Review
- Role of fibroblast growth factor receptor signaling in kidney development.American journal of physiology. Renal physiology · 2011Review
- Independent roles of Fgfr2 and Frs2alpha in ureteric epithelium.Development (Cambridge, England) · 2011Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
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 2alpha (Frs2alpha) is a major docking protein for Fgfr2 with downstream targets including Ets variant (Etv) 4 and Etv5 in other systems. Furthermore, global deletion of Frs2alpha causes early embryonic lethality. The purpose of the study was to determine the role of Frs2alpha in mediating Fgfr2 signaling in the ureteric epithelium. To that end, we generated mice with conditional deletion of Frs2alpha in the ureteric epithelium (Frs2alpha(UB-/-)) and mice with point mutations in the Frs2alpha binding site of Fgfr2 (Fgfr2(LR/LR)). Frs2alpha(UB-/-) 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(LR/LR) mice. Interestingly, Etv4 and Etv5 expression was unaltered in Frs2alpha(UB-/-) mice, as was Sprouty1, an antagonist of Frs2alpha 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 Frs2alpha in the ureteric epithelium. Furthermore, Frs2alpha may transmit signals through other receptor kinases present in ureteric epithelium. Finally, the renal hypoplasia observed in Frs2alpha(UB-/-) mice is likely secondary to decreased Ret and Wnt11 expression.
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