ArticleBMC developmental biology2015
Muscleblind-like 1 is required for normal heart valve development in vivo.
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.
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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.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects.PloS one · 2019Pooled it
- BMPR2 affects valve development via ECM-receptor interaction in zebrafish.Frontiers in cell and developmental biology · 2026Article
- Light-Sheet Imaging to Reveal Cardiac Structure in Rodent Hearts.Journal of visualized experiments : JoVE · 2024Article
- 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 · 2021Article
- Molecular functions and specific roles of circRNAs in the cardiovascular system.Non-coding RNA research · 2018Review
- Myotonic Dystrophy and Developmental Regulation of RNA Processing.Comprehensive Physiology · 2018Review
- Increased Hemodynamic Load in Early Embryonic Stages Alters Endocardial to Mesenchymal Transition.Frontiers in physiology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
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.
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