ArticleDevelopmental biology2011
Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions.
Article in Developmental biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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.
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.
Who cites it
73 citing papers in PubMed, 103 citations in OpenAlex.
- Animal models of hypoplastic left heart syndrome: genetic and anatomical approaches.Pediatric research · 2026Review
- RBFOX2-dependent alternative splicing of Numb regulates Notch signaling during muscle stem cell activation.Stem cell reports · 2026Article
- 3D spatial organization of heterogeneous nkx2.5+ progenitors in the zebrafish heart field pre-patterns cardiovascular development.Nature communications · 2025Article
- Article
- RBFOX2 induces osteogenic differentiation by Jph2 expression in MC3T3-E1 preosteoblast cells.Molecular biology reports · 2025Article
- Alternative splicing factors and cardiac disease: more than just missplicing?RNA (New York, N.Y.) · 2025Article
- RNA binding protein with multiple splicing (RBPMS) promotes contractile phenotype splicing in human embryonic stem cell-derived vascular smooth muscle cells.Cardiovascular research · 2024Article
- The 1000 Chinese Indigenous Pig Genomes Project provides insights into the genomic architecture of pigs.Nature communications · 2024Article
- RNA splicing factor RBFOX2 is a key factor in the progression of cancer and cardiomyopathy.Clinical and translational medicine · 2024Review
- Loss of insulin receptor isoform B impairs proinsulin processing in pancreatic β cells.Metabolism open · 2024Article
- The Biological Mechanisms and Clinical Roles of RNA-Binding Proteins in Cardiovascular Diseases.Biomolecules · 2024Review
- RNA-binding proteins in cardiovascular biology and disease: the beat goes on.Nature reviews. Cardiology · 2024Review
- Triptolide, a Cancer Cell Proliferation Inhibitor, Causes Zebrafish Muscle Defects by Regulating Notch and STAT3 Signaling Pathways.International journal of molecular sciences · 2024Article
- Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in two zebrafish models.Translational psychiatry · 2024Article
- RNA binding proteins in cardiovascular development and disease.Current topics in developmental biology · 2024Article
- RNA binding proteins as mediators of pathological cardiac remodeling.Frontiers in cell and developmental biology · 2024Review
- Pleiotropic contribution ofbioRxiv : the preprint server for biology · 2023Article
- Hypoplastic Left Heart Syndrome: Signaling & Molecular Perspectives, and the Road Ahead.International journal of molecular sciences · 2023Review
- Loss of YTHDF2 Alters the Expression of mJACC. Basic to translational science · 2023Article
- Effects of non-coding RNAs and RNA-binding proteins on mitochondrial dysfunction in diabetic cardiomyopathy.Frontiers in cardiovascular medicine · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Rbfox RNA binding proteins are implicated as regulators of phylogenetically-conserved alternative splicing events important for muscle function. To investigate the function of rbfox genes, we used morpholino-mediated knockdown of muscle-expressed rbfox1l and rbfox2 in zebrafish embryos. Single and double morphant embryos exhibited changes in splicing of overlapping sets of bioinformatically-predicted rbfox target exons, many of which exhibit a muscle-enriched splicing pattern that is conserved in vertebrates. Thus, conservation of intronic Rbfox binding motifs is a good predictor of Rbfox-regulated alternative splicing. Morphology and development of single morphant embryos were strikingly normal; however, muscle development in double morphants was severely disrupted. Defects in cardiac muscle were marked by reduced heart rate and in skeletal muscle by complete paralysis. The predominance of wavy myofibers and abnormal thick and thin filaments in skeletal muscle revealed that myofibril assembly is defective and disorganized in double morphants. Ultra-structural analysis revealed that although sarcomeres with electron dense M- and Z-bands are present in muscle fibers of rbfox1l/rbox2 morphants, they are substantially reduced in number and alignment. Importantly, splicing changes and morphological defects were rescued by expression of morpholino-resistant rbfox cDNA. Additionally, a target-blocking MO complementary to a single UGCAUG motif adjacent to an rbfox target exon of fxr1 inhibited inclusion in a similar manner to rbfox knockdown, providing evidence that Rbfox regulates the splicing of target exons via direct binding to intronic regulatory motifs. We conclude that Rbfox proteins regulate an alternative splicing program essential for vertebrate heart and skeletal muscle functions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.