ArticlePloS one2013
Deletion of fibroblast growth factor receptor 2 from the peri-wolffian duct stroma leads to ureteric induction abnormalities and vesicoureteral reflux.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Loss of Fibroblast Growth Factor Receptor 2 (FGFR2) Leads to Defective Bladder Urothelial Regeneration after Cyclophosphamide Injury.The American journal of pathology · 2021Article
- Association of vesicoureteral reflux and gastroesophageal reflux disease in children: A population-based study.Canadian Urological Association journal = Journal de l'Association des urologues du Canada · 2020Article
- FGF/FGFR2 Protects against Tubular Cell Death and Acute Kidney Injury Involving Erk1/2 Signaling Activation.Kidney diseases (Basel, Switzerland) · 2020Article
- Duplex kidney formation: developmental mechanisms and genetic predisposition.F1000Research · 2020Review
- Ablation of FGFR2 in Fibroblasts Ameliorates Kidney Fibrosis after Ischemia/Reperfusion Injury in Mice.Kidney diseases (Basel, Switzerland) · 2017Article
- Loss of peri-Wolffian duct stromal Frs2α expression in mice leads to abnormal ureteric bud induction and vesicoureteral reflux.Pediatric research · 2017Article
- Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux.Scientific reports · 2017Article
- 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
- 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
- Region-specific regulation of cell proliferation by FGF receptor signaling during the Wolffian duct development.Developmental biology · 2015Article
- Vesicoureteric reflux and reflux nephropathy: from mouse models to childhood disease.Pediatric nephrology (Berlin, Germany) · 2014Review
- GDNF-independent ureteric budding: role of PI3K-independent activation of AKT and FOSB/JUN/AP-1 signaling.Biology open · 2013Article
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9 authors at 4 institutions in 1 country.
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Abstract
purposePax3cre-mediated deletion of fibroblast growth factor receptor 2 (Fgfr2) broadly in renal and urinary tract mesenchyme led to ureteric bud (UB) induction defects and vesicoureteral reflux (VUR), although the mechanisms were unclear. Here, we investigated whether Fgfr2 acts specifically in peri-Wolffian duct stroma (ST) to regulate UB induction and development of VUR and the mechanisms of Fgfr2 activity.
methodsWe conditionally deleted Fgfr2 in ST (Fgfr2(ST-/-)) using Tbx18cre mice. To look for ureteric bud induction defects in young embryos, we assessed length and apoptosis of common nephric ducts (CNDs). We performed 3D reconstructions and histological analyses of urinary tracts of embryos and postnatal mice and cystograms in postnatal mice to test for VUR. We performed in situ hybridization and real-time PCR in young embryos to determine mechanisms underlying UB induction defects.
resultsWe confirmed that Fgfr2 is expressed in ST and that Fgfr2 was efficiently deleted in this tissue in Fgfr2(ST-/-) mice at embryonic day (E) 10.5. E11.5 Fgfr2(ST-/-) mice had randomized UB induction sites with approximately 1/3 arising too high and 1/3 too low from the Wolffian duct; however, apoptosis was unaltered in E12.5 mutant CNDs. While ureters were histologically normal, E15.5 Fgfr2(ST-/-) mice exhibit improper ureteral insertion sites into the bladder, consistent with the ureteric induction defects. While ureter and bladder histology appeared normal, postnatal day (P) 1 mutants had high rates of VUR versus controls (75% versus 3%, p = 0.001) and occasionally other defects including renal hypoplasia and duplex systems. P1 mutant mice also had improper ureteral bladder insertion sites and shortened intravesicular tunnel lengths that correlated with VUR. E10.5 Fgfr2(ST-/-) mice had decreases in Bmp4 mRNA in stromal tissues, suggesting a mechanism underlying the ureteric induction and VUR phenotypes.
conclusionMutations in FGFR2 could possibly cause VUR in humans.
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