Evidence map›Paper›PMID 26722124›Full record

ArticleJournal of the American Heart Association2015

Rac1 Signaling Is Required for Anterior Second Heart Field Cellular Organization and Cardiac Outflow Tract Development.

Carmen Leung, Yin Liu, Xiangru Lu, Mella Kim, Thomas A Drysdale, Qingping Feng

Open access · goldAbstract read
In one paragraph

Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

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  14. AFrontiers in pediatrics · 2019
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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

6 authors at 2 institutions in 1 country.

Carmen LeungDepartments of Physiology and Pharmacology, Medicine and Pediatrics, Schulich School of Medicine and Dentistry, Collaborative Program in Developmental Biology, Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada (C.L., Y.L., X.L., M.K., T.A.D., Q.F.).
Yin LiuDepartments of Physiology and Pharmacology, Medicine and Pediatrics, Schulich School of Medicine and Dentistry, Collaborative Program in Developmental Biology, Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada (C.L., Y.L., X.L., M.K., T.A.D., Q.F.).
Xiangru LuDepartments of Physiology and Pharmacology, Medicine and Pediatrics, Schulich School of Medicine and Dentistry, Collaborative Program in Developmental Biology, Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada (C.L., Y.L., X.L., M.K., T.A.D., Q.F.).
Mella KimDepartments of Physiology and Pharmacology, Medicine and Pediatrics, Schulich School of Medicine and Dentistry, Collaborative Program in Developmental Biology, Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada (C.L., Y.L., X.L., M.K., T.A.D., Q.F.).
Thomas A DrysdaleDepartments of Physiology and Pharmacology, Medicine and Pediatrics, Schulich School of Medicine and Dentistry, Collaborative Program in Developmental Biology, Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada (C.L., Y.L., X.L., M.K., T.A.D., Q.F.).
Qingping FengDepartments of Physiology and Pharmacology, Medicine and Pediatrics, Schulich School of Medicine and Dentistry, Collaborative Program in Developmental Biology, Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada (C.L., Y.L., X.L., M.K., T.A.D., Q.F.).
Children’s Health Research Institute · CAWestern University · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

backgroundThe small GTPase Rac1 regulates diverse cellular functions, including both apicobasal and planar cell polarity pathways; however, its role in cardiac outflow tract (OFT) development remains unknown. In the present study, we aimed to examine the role of Rac1 in the anterior second heart field (SHF) splanchnic mesoderm and subsequent OFT development during heart morphogenesis. METHODS AND

resultsUsing the Cre/loxP system, mice with an anterior SHF-specific deletion of Rac1 (Rac1(SHF)) were generated. Embryos were collected at various developmental time points for immunostaining and histological analysis. Intrauterine echocardiography was also performed to assess aortic valve blood flow in embryos at embryonic day 18.5. The Rac1(SHF) splanchnic mesoderm exhibited disruptions in SHF progenitor cellular organization and proliferation. Consequently, this led to a spectrum of OFT defects along with aortic valve defects in Rac1(SHF) embryos. Mechanistically, it was found that the ability of the Rac1(SHF) OFT myocardial cells to migrate into the proximal OFT cushion was severely reduced. In addition, expression of the neural crest chemoattractant semaphorin 3c was decreased. Lineage tracing showed that anterior SHF contribution to the OFT myocardium and aortic valves was deficient in Rac1(SHF) hearts. Furthermore, functional analysis with intrauterine echocardiography at embryonic day 18.5 showed aortic valve regurgitation in Rac1(SHF) hearts, which was not seen in control hearts.

conclusionsDisruptions of Rac1 signaling in the anterior SHF results in aberrant progenitor cellular organization and defects in OFT development. Our data show Rac1 signaling to be a critical regulator of cardiac OFT formation during embryonic heart development.

Indexed as

AnimalsAortic ValveAortic Valve InsufficiencyCell LineageCell MovementGene Expression Regulation, DevelopmentalGenetic Predisposition to DiseaseGestational AgeHeart Defects, CongenitalMice, KnockoutMorphogenesisMyocardiumNeural CrestNeuropeptidesPhenotyperac1 GTP-Binding ProteinNeuropeptidesrac1 GTP-Binding ProteinRac1 protein, mousesemaphorin 3C protein, mouseSemaphorinscellular organizationcongenital heart defectoutflow tract developmentRac1

Identifiers

PMID26722124
PMCPMC4859369
OpenAlexW2222592264

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.