ArticleCirculation research2007
Depletion of zebrafish titin reduces cardiac contractility by disrupting the assembly of Z-discs and A-bands.
Article in Circulation research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 89 citations in OpenAlex.
- Location-Dependent Differences in Cardiac and Skeletal Muscle Dysfunction Associated With Truncating Titin (Circulation research · 2026Article
- Molecular identifiers of the evolutionarily conserved titin pseudokinase.The Biochemical journal · 2026Article
- Deregulated nutrient response in ttntv cardiomyopathy can be repaired via Erk inhibition for cardioprotective effects.Journal of molecular and cellular cardiology · 2025Article
- Cartilaginous fish and mammalian connectin evolved independently from an ancestral bony fish-like structure.Scientific reports · 2025Article
- The Ancestor and Evolution of the Giant Muscle Protein Connectin/Titin.Journal of molecular evolution · 2025Article
- Transient titin-dependent ventricular defects during development lead to adult atrial arrhythmia and impaired contractility.iScience · 2024Article
- Loss of connectin novex-3 leads to heart dysfunction associated with impaired cardiomyocyte proliferation and abnormal nuclear mechanics.Scientific reports · 2024Article
- Allelic heterogeneity of TTNtv dilated cardiomyopathy can be modeled in adult zebrafish.JCI insight · 2024Article
- Zebrafish as a Model for Cardiovascular and Metabolic Disease: The Future of Precision Medicine.Biomedicines · 2024Review
- Transcriptome studies of inherited dilated cardiomyopathies.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Sarcomere maturation: function acquisition, molecular mechanism, and interplay with other organelles.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Mechanisms ofJournal of cardiovascular development and disease · 2021Review
- Under construction: The dynamic assembly, maintenance, and degradation of the cardiac sarcomere.Journal of molecular and cellular cardiology · 2020Review
- Modeling Inherited Cardiomyopathies in Adult Zebrafish for Precision Medicine.Frontiers in physiology · 2020Review
- Perturbation of the titin/MURF1 signaling complex is associated with hypertrophic cardiomyopathy in a fish model and in human patients.Disease models & mechanisms · 2019Article
- Immunohistochemical Identification of Muscle Fiber Types in MiceBio-protocol · 2019Article
- The giant titin: how to evaluate its role in cardiomyopathies.Journal of muscle research and cell motility · 2019Review
- A genome-wide map of circular RNAs in adult zebrafish.Scientific reports · 2019Article
- Tris(1,3-dichloro-2-propyl) Phosphate Exposure During the Early-Blastula Stage Alters the Normal Trajectory of Zebrafish Embryogenesis.Environmental science & technology · 2018Article
- Robust activation of microhomology-mediated end joining for precision gene editing applications.PLoS genetics · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The genetic study of titin has been notoriously difficult because of its size and complicated alternative splicing routes. Here, we have used zebrafish as an animal model to investigate the functions of individual titin isoforms. We identified 2 titin orthologs in zebrafish, ttna and ttnb, and annotated the full-length genomic sequences for both genes. We found that ttna, but not ttnb, is required for sarcomere assembly in the heart as well as the subsequent establishment of cardiac contractility. In fact, ttna is the earliest sarcomeric mRNA that is expressed in the heart, which makes it an early molecular marker for cardiomyocyte differentiation. Surprisingly, ttna is required for later steps of sarcomere assembly, including the assembly of Z-discs and A-bands, but not for early steps such as the assembly of Z-bodies and nonstriated myosin filaments. Reduction of individual titin isoforms in vivo using morpholino-modified antisense oligonucleotides indicated that (1) both N2B exon-containing and N2A exon-containing isoforms of ttna are required for sarcomere assembly in the heart; (2) N2A exon-containing isoforms of both ttna and ttnb are required for sarcomere assembly in the somites; and (3) the N2B exon-containing isoforms of ttnb are expressed later than other titin isoforms and are probably involved in modulating their expression; however, these isoforms of ttnb are not required for sarcomere assembly. Collectively, our results reveal distinct functions of different titin isoforms and suggest that various phenotypes in "titinopathies" may be attributable to the disruption of different titin isoforms.
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Registered trials
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