Evidence map›Paper›PMID 25641696›Full record

ArticleDevelopmental biology2015

Fibroblast growth factor receptor-Frs2α signaling is critical for nephron progenitors.

Valeria Di Giovanni, Kenneth A Walker, Daniel Bushnell, Caitlin Schaefer, Sunder Sims-Lucas, Pawan Puri, Carlton M Bates

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. FGF/FGFR signaling in health and disease.Signal transduction and targeted therapy · 2020
    Review
  7. Article
  8. Sirtuin 5 Regulates Proximal Tubule Fatty Acid Oxidation to Protect against AKI.Journal of the American Society of Nephrology : JASN · 2019
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Endothelial marker-expressing stromal cells are critical for kidney formation.American journal of physiology. Renal physiology · 2017
    Article
  14. Article
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Valeria Di GiovanniDivision of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
Kenneth A WalkerDivision of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
Daniel BushnellDivision of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
Caitlin SchaeferDivision of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
Sunder Sims-LucasDivision of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
Pawan PuriDivision of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA.
Carlton M BatesDivision of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15201, USA; Rangos Research Center, Children׳s Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA. Electronic address: batescm@upmc.edu.
University of Pittsburgh · US

Funding

Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
BMP and FGF Signaling in kidney progenitor cellsR01DK087794 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI KREIDBERG, JORDAN A · 2010 to 2013
$1.5M
Role of Receptors in the Metanephric MesenchymeR01DK095748 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BATES, CARLTON MATTHEW · 2013 to 2016
$1.4M
Renal Stroma Derived Endothelial Precursors are Critical for Renal DevelopmentK01DK096996 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SIMS-LUCAS, SUNDER · 2013 to 2017
$557k
NIDDK NIH HHS DK087794-04NIDDK NIH HHS K01 DK096996NIDDK NIH HHS P30 DK079307NIDDK NIH HHS R01 DK087794NIDDK NIH HHS R01 DK095748NIDDK NIH HHS R01-DK095748
6 · The paper itself

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.

Indexed as

AnimalsApoptosisApoptosis Regulatory ProteinsFlow CytometryGene Expression Regulation, DevelopmentalMembrane ProteinsMesenchymal Stem CellsMiceMice, KnockoutMicroscopy, FluorescenceNephronsNuclear ProteinsPolymerase Chain ReactionReceptors, NotchSignal TransductionTrans-ActivatorsApoptosis Regulatory ProteinsCited1 protein, mouseFRS2alpha protein, mouseMembrane ProteinsNuclear ProteinsReceptors, NotchTrans-ActivatorsFibroblast growth factor receptorsFrs2αKidney developmentNephron progenitors

Identifiers

PMID25641696
PMCPMC4361332
OpenAlexW2025503796

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.