Evidence map›Paper›PMID 26472242›Full record

ArticleBMC developmental biology2015

Muscleblind-like 1 is required for normal heart valve development in vivo.

Ryan J Coram, Samantha J Stillwagon, Anuradha Guggilam, Michael W Jenkins, Maurice S Swanson, Andrea N Ladd

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 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. BMPR2 affects valve development via ECM-receptor interaction in zebrafish.Frontiers in cell and developmental biology · 2026
    Article
  3. Light-Sheet Imaging to Reveal Cardiac Structure in Rodent Hearts.Journal of visualized experiments : JoVE · 2024
    Article
  4. Inhibition of lncRNA MAAT Controls Multiple Types of Muscle Atrophy by cis- and trans-Regulatory Actions.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  5. Review
  6. Review
  7. 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

6 authors at 3 institutions in 1 country.

Ryan J CoramDepartment of Cellular & Molecular Medicine, Lerner Research Institute, 9500 Euclid Ave. NC10, Cleveland Clinic, Cleveland, OH, 44195, USA. ryan_coram@yahoo.com.
Samantha J StillwagonDepartment of Cellular & Molecular Medicine, Lerner Research Institute, 9500 Euclid Ave. NC10, Cleveland Clinic, Cleveland, OH, 44195, USA. stillws@ccf.org.
Anuradha GuggilamDepartment of Cellular & Molecular Medicine, Lerner Research Institute, 9500 Euclid Ave. NC10, Cleveland Clinic, Cleveland, OH, 44195, USA. guggila@ccf.org.
Michael W JenkinsDepartment of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. mwj5@case.edu.
Maurice S SwansonDepartment of Molecular Genetics & Microbiology, College of Medicine, Center for NeuroGenetics and the Genetics Institute, University of Florida, Gainesville, FL, 32610, USA. mswanson@ufl.edu.
Andrea N LaddDepartment of Cellular & Molecular Medicine, Lerner Research Institute, 9500 Euclid Ave. NC10, Cleveland Clinic, Cleveland, OH, 44195, USA. ladda@ccf.org.
Cleveland Clinic Lerner College of Medicine · USUniversity of Florida · USUniversity School · US

Funding

Temporal/spatial RNA Expression Effects in DM1 and DM2P01NS058901 · NINDS · UNIVERSITY OF MINNESOTA · PI RANUM, LAURA P.W · 2008 to 2017
$12.3M
RNA DOMINANCE IN HUMAN DISEASER01AR046799 · NIAMS · UNIVERSITY OF FLORIDA · PI SWANSON, MAURICE SCOTT · 2000 to 2014
$4.2M
Role of pre-mRNA alternative splicing programs in heart and muscle developmentR01HL089376 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI LADD, ANDREA NICOLE · 2009 to 2014
$1.7M
Optical pacing of the embryonic heartR21HL115373 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI JENKINS, MICHAEL W. · 2012 to 2013
$422k
NHLBI NIH HHS R01 HL089376NHLBI NIH HHS R01HL089376NHLBI NIH HHS R21 HL115373NHLBI NIH HHS R21HL115373NIAMS NIH HHS R01 AR046799NIAMS NIH HHS R01AR046799NINDS NIH HHS P01 NS058901NINDS NIH HHS P01NS058901
6 · The paper itself

Abstract

backgroundDevelopment of the valves and septa of the heart depends on the formation and remodeling of the endocardial cushions in the atrioventricular canal and outflow tract. These cushions are populated by mesenchyme produced from the endocardium by epithelial-mesenchymal transition (EMT). The endocardial cushions are remodeled into the valves at post-EMT stages via differentiation of the mesenchyme and changes in the extracellular matrix (ECM). Transforming growth factor β (TGFβ) signaling has been implicated in both the induction of EMT in the endocardial cushions and the remodeling of the valves at post-EMT stages. We previously identified the RNA binding protein muscleblind-like 1 (MBNL1) as a negative regulator of TGFβ signaling and EMT in chicken endocardial cushions ex vivo. Here, we investigate the role of MBNL1 in endocardial cushion development and valvulogenesis in Mbnl1(∆E3/∆E3) mice, which are null for MBNL1 protein.

methodsCollagen gel invasion assays, histology, immunohistochemistry, real-time RT-PCR, optical coherence tomography, and echocardiography were used to evaluate EMT and TGFβ signaling in the endocardial cushions, and morphogenesis, ECM composition, and function of the heart valves.

resultsAs in chicken, the loss of MBNL1 promotes precocious TGFβ signaling and EMT in the endocardial cushions. Surprisingly, this does not lead to the production of excess mesenchyme, but later valve morphogenesis is aberrant. Adult Mbnl1(∆E3/∆E3) mice exhibit valve dysmorphia with elevated TGFβ signaling, changes in ECM composition, and increased pigmentation. This is accompanied by a high incidence of regurgitation across both inflow and outflow valves. Mbnl1(∆E3/∆E3) mice also have a high incidence of ostium secundum septal defects accompanied by atrial communication, but do not develop overt cardiomyopathy.

conclusionsTogether, these data indicate that MBNL1 plays a conserved role in negatively regulating TGFβ signaling, and is required for normal valve morphogenesis and homeostasis in vivo.

Indexed as

OrganogenesisSignal TransductionAnimalsDNA-Binding ProteinsEndocardial CushionsEpithelial-Mesenchymal TransitionHeartHeart ValvesMiceRNA-Binding ProteinsTransforming Growth Factor betaDNA-Binding ProteinsMbnl1 protein, mouseRNA-Binding ProteinsTransforming Growth Factor beta

Identifiers

PMID26472242
PMCPMC4608261
OpenAlexW2109695131

What OpenQuestion holds

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LicenceCC BY
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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.