Evidence map›Paper›PMID 26134413›Full record

ArticleBMC developmental biology2015

FOXL2 modulates cartilage, skeletal development and IGF1-dependent growth in mice.

Mara Marongiu, Loredana Marcia, Emanuele Pelosi, Mario Lovicu, Manila Deiana, Yonqing Zhang, Alessandro Puddu, Angela Loi, Manuela Uda, Antonino Forabosco and 2 more

Open access · hybridAbstract read
In one paragraph

Article in BMC developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Canine XX Disorders/Differences of Sex Development (SRY-Negative): A Potential Role for theSexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. FOXO1 mitigates the SMAD3/FOXL2Journal of translational medicine · 2021
    Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
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

12 authors at 1 institution in 1 country.

Mara MarongiuIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, SS 554 km 4500, Monserrato, 09042, Italy. mara.marongiu@irgb.cnr.it.
Loredana MarciaIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, SS 554 km 4500, Monserrato, 09042, Italy. loredana.marcia@irgb.cnr.it.
Emanuele PelosiLaboratory of Genetics, NIA-IRP, NIH, Baltimore, MD, USA. pelosie@grc.nia.nih.gov.
Mario LovicuIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, SS 554 km 4500, Monserrato, 09042, Italy. mario.lovicu@irgb.cnr.it.
Manila DeianaIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, SS 554 km 4500, Monserrato, 09042, Italy. manila.deiana@irgb.cnr.it.
Yonqing ZhangLaboratory of Genetics, NIA-IRP, NIH, Baltimore, MD, USA. zhangyon@mail.nih.gov.
Alessandro PudduIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, SS 554 km 4500, Monserrato, 09042, Italy. alepud@gmail.com.
Angela LoiIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, SS 554 km 4500, Monserrato, 09042, Italy. angela.loi@irgb.cnr.it.
Manuela UdaIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, SS 554 km 4500, Monserrato, 09042, Italy. manuela.uda@irgb.cnr.it.
Antonino ForaboscoCante di Montevecchio Association, Genomic Research Center, Fano, Italy. bordiga34@gmail.com.
David SchlessingerLaboratory of Genetics, NIA-IRP, NIH, Baltimore, MD, USA. SchlessingerD@grc.nia.nih.gov.
Laura CrisponiIstituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, SS 554 km 4500, Monserrato, 09042, Italy. laura.crisponi@irgb.cnr.it.
Institute of Genetic and Biomedical Research · IT

Funding

Placenta specific and ribosomal RNA genes: structure and functionZIAAG000646 · NIA · NATIONAL INSTITUTE ON AGING · PI NAGARAJA, RAMAIAH · 2009 to 2025
$12.9M
Genes Associated With Ovarian Development and Premature Ovarian Failure - testZIAAG000647 · NIA · NATIONAL INSTITUTE ON AGING · PI SCHLESSINGER, DAVID · 2009 to 2017
$6.2M
Telethon GP0049Y01
6 · The paper itself

Abstract

backgroundHaploinsufficiency of the FOXL2 transcription factor in humans causes Blepharophimosis/Ptosis/Epicanthus Inversus syndrome (BPES), characterized by eyelid anomalies and premature ovarian failure. Mice lacking Foxl2 recapitulate human eyelid/forehead defects and undergo female gonadal dysgenesis. We report here that mice lacking Foxl2 also show defects in postnatal growth and embryonic bone and cartilage formation.

methodsFoxl2 (-/-) male mice at different stages of development have been characterized and compared to wild type. Body length and weight were measured and growth curves were created. Skeletons were stained with alcian blue and/or alizarin red. Bone and cartilage formation was analyzed by Von Kossa staining and immunofluorescence using anti-FOXL2 and anti-SOX9 antibodies followed by confocal microscopy. Genes differentially expressed in skull vaults were evaluated by microarray analysis. Analysis of the GH/IGF1 pathway was done evaluating the expression of several hypothalamic-pituitary-bone axis markers by RT-qPCR.

resultsCompared to wild-type, Foxl2 null mice are smaller and show skeletal abnormalities and defects in cartilage and bone mineralization, with down-regulation of the GH/IGF1 axis. Consistent with these effects, we find FOXL2 expressed in embryos at 9.5 dpc in neural tube epithelium, in head mesenchyme near the neural tube, and within the first branchial arch; then, starting at 12.5 dpc, expressed in cartilaginous tissue; and at PO and P7, in hypothalamus.

conclusionsOur results support FOXL2 as a master transcription factor in a spectrum of developmental processes, including growth, cartilage and bone formation. Its action overlaps that of SOX9, though they are antagonistic in female vs male gonadal sex determination but conjoint in cartilage and skeletal development.

Indexed as

Bone DevelopmentSignal TransductionAnimalsBlepharophimosisCartilageFemaleForkhead Box Protein L2Forkhead Transcription FactorsHumansInsulin-Like Growth Factor IMaleMiceSkin AbnormalitiesUrogenital AbnormalitiesForkhead Box Protein L2Forkhead Transcription FactorsFoxl2 protein, mouseinsulin-like growth factor-1, mouseInsulin-Like Growth Factor I

Identifiers

PMID26134413
PMCPMC4489133
OpenAlexW1599020614

What OpenQuestion holds

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LicenceCC BY
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.