ArticleDevelopmental biology2015
Fibroblast growth factor receptor-Frs2α signaling is critical for nephron progenitors.
Article in Developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Transcription factors ETV4 and ETV5 are required for nephron progenitor cell maintenance, distal nephron development and connection to the collecting system.Frontiers in cell and developmental biology · 2026Article
- Shared features in ear and kidney development - implications for oto-renal syndromes.Disease models & mechanisms · 2024Article
- Elevated Protein Kinase A Activity in Stomach Mesenchyme Disrupts Mesenchymal-epithelial Crosstalk and Induces Preneoplasia.Cellular and molecular gastroenterology and hepatology · 2022Article
- Single-cell RNA sequencing reveals differential cell cycle activity in key cell populations during nephrogenesis.Scientific reports · 2021Article
- Review
- FGF/FGFR signaling in health and disease.Signal transduction and targeted therapy · 2020Review
- Whole genome sequencing and novel candidate genes for CAKUT and altered nephrogenesis in the HSRA rat.Physiological genomics · 2020Article
- Sirtuin 5 Regulates Proximal Tubule Fatty Acid Oxidation to Protect against AKI.Journal of the American Society of Nephrology : JASN · 2019Article
- Molecular characterization of nephron progenitors and their early epithelial derivative structures in the nephrogenic zone of the canine fetal kidney.European journal of histochemistry : EJH · 2019Article
- Ectopic Phosphorylated Creb Marks Dedifferentiated Proximal Tubules in Cystic Kidney Disease.The American journal of pathology · 2018Article
- Regulation of Renal Differentiation by Trophic Factors.Frontiers in physiology · 2018Review
- Loss of peri-Wolffian duct stromal Frs2α expression in mice leads to abnormal ureteric bud induction and vesicoureteral reflux.Pediatric research · 2017Article
- Endothelial marker-expressing stromal cells are critical for kidney formation.American journal of physiology. Renal physiology · 2017Article
- 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
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Previous studies using transgenic Pax3cre mice have revealed roles for fibroblast growth factor receptors (Fgfrs) and Fgfr substrate 2α (Frs2α) signaling in early metanephric mesenchyme patterning and in ureteric morphogenesis. The role of Fgfr/Frs2α signaling in nephron progenitors is unknown. Thus, we generated mouse models using BAC transgenic Six2EGFPcre (Six2cre) mediated deletion of Fgfrs and/or Frs2α in nephron progenitors. Six2cre mediated deletion of Fgfr1 or Fgfr2 alone led to no obvious kidney defects. Six2creFgfr1(flox/flox)Fgfr2(flox/flox) (Fgfr1/2(NP-/-)) mice generate a discernable kidney; however, they develop nephron progenitor depletion starting at embryonic day 12.5 (E12.5) and later demonstrate severe cystic dysplasia. To determine the role of Frs2α signaling downstream of Fgfr2 in Fgfr1/2(NP-/-) mice, we generated Six2cre(,)Fgfr1(flox/flox)Fgfr2(LR/LR) (Fgfr1(NP-/-)Fgfr2(LR/LR)) mice that have point mutations in the Frs2α binding site of Fgfr2. Like Fgfr1/2(NP-/-) mice, Fgfr1(NP-/-)Fgfr2(LR/LR) develop nephron progenitor depletion, but it does not start until E14.5 and older mice have less severe cystic dysplasia than Fgfr1/2(NP-/-) To determine the role of Frs2α alone in nephron progenitors, we generated Six2creFrs2'A(flox/flox) (Frs2a(NP-/-)) mice. Frs2a(NP-/-)mice also develop nephron progenitor depletion and renal cysts, although these occurred later and were less severe than in the other Six2cre mutant mice. The nephron progenitor loss in all Six2cre mutant lines was associated with decreased Cited1 expression and increased apoptosis versus controls. FAC-sorted nephron progenitors in Six2cre Frs2'A(flox/flox) mice demonstrated evidence of increased Notch activity versus controls, which likely drives the progenitor defects. Thus, Fgfr1 and Fgfr2 have synergistic roles in maintaining nephron progenitors; furthermore, Fgfr signaling in nephron progenitors appears to be mediated predominantly by Frs2α.
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