ArticleJournal of the American Society of Nephrology : JASN2012
Ureteric morphogenesis requires Fgfr1 and Fgfr2/Frs2α signaling in the metanephric mesenchyme.
Article in Journal of the American Society of Nephrology : JASN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Hedgehog signaling is required for the maintenance of mesenchymal nephron progenitors.bioRxiv : the preprint server for biology · 2024Article
- Shared features in ear and kidney development - implications for oto-renal syndromes.Disease models & mechanisms · 2024Article
- FGF/FGFR2 Protects against Tubular Cell Death and Acute Kidney Injury Involving Erk1/2 Signaling Activation.Kidney diseases (Basel, Switzerland) · 2020Article
- Regulation of Renal Differentiation by Trophic Factors.Frontiers in physiology · 2018Review
- Ectopic Phosphorylated Creb Marks Dedifferentiated Proximal Tubules in Cystic Kidney Disease.The American journal of pathology · 2018Article
- Loss of peri-Wolffian duct stromal Frs2α expression in mice leads to abnormal ureteric bud induction and vesicoureteral reflux.Pediatric research · 2017Article
- Afadin orients cell division to position the tubule lumen in developing renal tubules.Development (Cambridge, England) · 2017Article
- Fgfr2 is integral for bladder mesenchyme patterning and function.American journal of physiology. Renal physiology · 2017Article
- Making new kidneys: On the road from science fiction to science fact.Current opinion in organ transplantation · 2016Review
- Six2creFrs2α knockout mice are a novel model of renal cystogenesis.Scientific reports · 2016Article
- 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
- Region-specific regulation of cell proliferation by FGF receptor signaling during the Wolffian duct development.Developmental biology · 2015Article
- Fibroblast growth factor receptor-Frs2α signaling is critical for nephron progenitors.Developmental biology · 2015Article
- Ablation of the renal stroma defines its critical role in nephron progenitor and vasculature patterning.PloS one · 2014Article
- Cold induced sweating syndrome with urinary system anomaly association.Case reports in pediatrics · 2013Article
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6 authors at 2 institutions in 1 country.
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Abstract
Conditional deletion of fibroblast growth factor receptors (Fgfrs) 1 and 2 in the metanephric mesenchyme (MM) of mice leads to a virtual absence of MM and unbranched ureteric buds that are occasionally duplex. Deletion of Fgfr2 in the MM leads to kidneys with cranially displaced ureteric buds along the Wolffian duct or duplex ureters. Mice with point mutations in Fgfr2's binding site for the docking protein Frs2α (Fgfr2(LR/LR)), however, have normal kidneys; the roles of the Fgfr2/Frs2α signaling axis in MM development and regulating the ureteric bud induction site are incompletely understood. Here, we generated mice with both Fgfr1 deleted in the MM and Fgfr2(LR/LR) point mutations (Fgfr1(Mes-/-)Fgfrf2(LR/LR)). Unlike mice lacking both Fgfr1 and Fgfr2 in the MM, these mice had no obvious MM defects but had cranially displaced or duplex ureteric buds, probably as a result of decreased Bmp4 expression. Fgfr1(Mes-/-)Fgfr2(LR/LR) mice also had subsequent defects in ureteric morphogenesis, including dilated, hyperproliferative tips and decreased branching. Ultimately, they developed progressive renal cystic dysplasia associated with abnormally oriented cell division. Furthermore, mutants had increased and ectopic expression of Ret and its downstream targets in ureteric trunks, and exhibited upregulation of Ret/Etv4/5 signaling effectors, including Met, Myb, Cxcr4, and Crlf1. These defects were associated with reduced expression of Bmp4 in mesenchymal cells near mutant ureteric bud tips. Taken together, these results demonstrate that Fgfr2/Frs2α signaling in the MM promotes Bmp4 expression, which represses Ret levels and signaling in the ureteric bud to ensure normal ureteric morphogenesis.
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