Evidence map›Paper›PMID 23382810›Full record

ArticlePloS one2013

BMP-mediated functional cooperation between Dlx5;Dlx6 and Msx1;Msx2 during mammalian limb development.

Maxence Vieux-Rochas, Kamal Bouhali, Stefano Mantero, Giulia Garaffo, Paolo Provero, Simonetta Astigiano, Ottavia Barbieri, Mariano F Caratozzolo, Apollonia Tullo, Luisa Guerrini and 4 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

20 citing papers in PubMed, 45 citations in OpenAlex.

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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

14 authors at 9 institutions in 3 countries.

Maxence Vieux-RochasEvolution des Régulations Endocriniennes, Centre national de la recherche scientifique, UMR-7221, Muséum National d'Histoire Naturelle, Paris, France.
Kamal Bouhali
Stefano Mantero
Giulia Garaffo
Paolo Provero
Simonetta Astigiano
Ottavia Barbieri
Mariano F Caratozzolo
Apollonia Tullo
Luisa Guerrini
Yvan Lallemand
Benoît Robert
Giovanni Levi
Giorgio R Merlo
Evolution des Régulations Endocriniennes · FRGénétique Moléculaire Génomique Microbiologie · FRMedical Technologies (Czechia) · CZUniversity of Turin · ITDulbecco Telethon Institute · ITFondazione Humanitas per la Ricerca · ITOspedale Policlinico San Martino · ITUniversity of Genoa · ITUniversity of Milan · IT

Funding

Telethon GGP11097Telethon GP0218Y01Telethon TCR07004
6 · The paper itself

Abstract

The Dlx and Msx homeodomain transcription factors play important roles in the control of limb development. The combined disruption of Msx1 and Msx2, as well as that of Dlx5 and Dlx6, lead to limb patterning defects with anomalies in digit number and shape. Msx1;Msx2 double mutants are characterized by the loss of derivatives of the anterior limb mesoderm which is not observed in either of the simple mutants. Dlx5;Dlx6 double mutants exhibit hindlimb ectrodactyly. While the morphogenetic action of Msx genes seems to involve the BMP molecules, the mode of action of Dlx genes still remains elusive. Here, examining the limb phenotypes of combined Dlx and Msx mutants we reveal a new Dlx-Msx regulatory loop directly involving BMPs. In Msx1;Dlx5;Dlx6 triple mutant mice (TKO), beside the expected ectrodactyly, we also observe the hallmark morphological anomalies of Msx1;Msx2 double mutants suggesting an epistatic role of Dlx5 and Dlx6 over Msx2. In Msx2;Dlx5;Dlx6 TKO mice we only observe an aggravation of the ectrodactyly defect without changes in the number of the individual components of the limb. Using a combination of qPCR, ChIP and bioinformatic analyses, we identify two Dlx/Msx regulatory pathways: 1) in the anterior limb mesoderm a non-cell autonomous Msx-Dlx regulatory loop involves BMP molecules through the AER and 2) in AER cells and, at later stages, in the limb mesoderm the regulation of Msx2 by Dlx5 and Dlx6 occurs also cell autonomously. These data bring new elements to decipher the complex AER-mesoderm dialogue that takes place during limb development and provide clues to understanding the etiology of congenital limb malformations.

Indexed as

AnimalsBone Morphogenetic ProteinsEctodermExtremitiesFemaleGene Expression Regulation, DevelopmentalGene Regulatory NetworksHomeodomain ProteinsMesodermMiceMorphogenesisMSX1 Transcription FactorMutationBone Morphogenetic ProteinsDlx5 protein, mouseDlx6 protein, mouseHomeodomain ProteinsMsx1 protein, mouseMSX1 Transcription FactorMSX2 protein

Identifiers

PMID23382810
PMCPMC3558506
OpenAlexW2016288300

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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.