Evidence map›Paper›PMID 16267055›Full record

ArticleThe Journal of biological chemistry2006

Fgfr4 is required for effective muscle regeneration in vivo. Delineation of a MyoD-Tead2-Fgfr4 transcriptional pathway.

Po Zhao, Giuseppina Caretti, Stephanie Mitchell, Wallace L McKeehan, Adele L Boskey, Lauren M Pachman, Vittorio Sartorelli, Eric P Hoffman

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

61 citing papers in PubMed, 120 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Ablation of UCP-1+ cells impacts FAP dynamics in muscle regeneration.American journal of physiology. Cell physiology · 2025
    Article
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  7. Review
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  11. Review
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  17. Review
  18. Article
  19. Editorial: Resident and Ectopic FGF Signaling in Development and Disease.Frontiers in cell and developmental biology · 2020
    Article
  20. Review

1 more citing papers are in PubMed but not listed here.

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

8 authors at 6 institutions in 1 country.

Po ZhaoResearch Center for Genetic Medicine, Children's National Medical Center, Washington, DC 20010, USA.
Giuseppina Caretti
Stephanie Mitchell
Wallace L McKeehan
Adele L Boskey
Lauren M Pachman
Vittorio Sartorelli
Eric P Hoffman
Children's National · USHospital for Special Surgery · USMemorial Medical Center · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · USNational Institutes of Health · USTexas A&M University System · US

Funding

YEAST ER MOLECULAR CHAPERONE TRANSLOCATION: GENOME DATABANK HOMOLOGSP41RR006009 · NCRR · MELLON PITTS CORPORATION (MPC CORP) · PI KNOLL, ERIC · 1990 to 2011
$22.0M
REGULATION OF MYOD POST TRANSCRIPTIONAL MODIFICATIONSZ01AR041126 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI SARTORELLI, VITTORIO · 2000 to 2008
$2.4M
HUMAN HEPATOCYTE GROWTH FACTORSR01DK035310 · NIDDK · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI MCKEEHAN, WALLACE LEE · 1986 to 2006
$1.9M
NCRR NIH HHS P41 RR006009NIDDK NIH HHS DK35310NIDDK NIH HHS R01 DK035310
6 · The paper itself

Abstract

Fgfr4 has been shown to be important for appropriate muscle development in chick limb buds; however, Fgfr4 null mice show no phenotype. Here, we show that staged induction of muscle regeneration in Fgfr4 null mice becomes highly abnormal at the time point when Fgfr4 is normally expressed. By 7 days of regeneration, differentiation of myotubes became poorly coordinated and delayed by both histology and embryonic myosin heavy chain staining. By 14 days much of the muscle was replaced by fat and calcifications. To begin to dissect the molecular pathways involving Fgfr4, we queried the promoter sequences for transcriptional factor binding sites and tested candidate regulators in a 27-time point regeneration series. The Fgfr4 promoter region contained a Tead protein binding site (M-CAT 5'-CATTCCT-3'), and Tead2 showed induction during regeneration commensurate with Fgfr4 regulation. Co-transfection of Tead2 and Fgfr4 promoter reporter constructs into C2C12 myotubes showed Tead2 to activate Fgfr4, and mutation of the M-CAT motif in the Fgfr4 promoter abolished these effects. Immunostaining for Tead2 showed timed expression in myotube nuclei consistent with the mRNA data. Query of the expression timing and genomic sequences of Tead2 suggested direct regulation by MyoD, and consistent with this, MyoD directly bound to two strong E-boxes in the first intron of Tead2 by chromatin immunoprecipitation assay. Moreover, co-transfection of MyoD and Tead2 intron reporter constructs into 10T1/2 cells activated reporter activity in a dose-dependent manner. This activation was greatly reduced when the two E-boxes were mutated. Our data suggest a novel MyoD-Tead2-Fgfr4 pathway important for effective muscle regeneration.

Indexed as

AnimalsCell DifferentiationDNA-Binding ProteinsIntronsMiceMice, Mutant StrainsMuscle, SkeletalMutagenesisMyoblasts, SkeletalMyoD ProteinPromoter Regions, GeneticReceptor, Fibroblast Growth Factor, Type 4RegenerationTEA Domain Transcription FactorsTranscription FactorsTranscription, GeneticDNA-Binding ProteinsFgfr4 protein, mouseMyoD1 myogenic differentiation proteinMyoD ProteinReceptor, Fibroblast Growth Factor, Type 4Tead2 protein, mouseTEA Domain Transcription FactorsTranscription Factors

Identifiers

PMID16267055
PMCPMC1892582
OpenAlexW1964292925

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.