ArticleThe Journal of cell biology2011
Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species.
Article in The Journal of cell biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- A meta-analysis of microRNA expression profiling studies in heart failure.Heart failure reviews · 2021Pooled it
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- Alternative cleavage and polyadenylation: key regulatory mechanisms in health and disease.RNA biology · 2025Review
- In Vivo Models of Cardiovascular Disease:Biomedicines · 2025Review
- Cardiac Tissue Bioprinting: Integrating Structure and Functions Through Biomimetic Design, Bioinks, and Stimulation.Gels (Basel, Switzerland) · 2025Review
- Animal models in biomedical research: Relevance ofHeliyon · 2025Review
- Molecular Regulation of Cardiac Conduction System Development.Current cardiology reports · 2024Review
- Cardiac Development and Factors Influencing the Development of Congenital Heart Defects (CHDs): Part I.International journal of molecular sciences · 2024Review
- Article
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- Inter-Species Rescue of Mutant Phenotype-The Standard for Genetic Analysis of Human Genetic Disorders inInternational journal of molecular sciences · 2022Review
- Transcriptional Control of Apical-Basal Polarity Regulators.International journal of molecular sciences · 2021Review
- New Insights into the Development and Morphogenesis of the Cardiac Purkinje Fiber Network: Linking Architecture and Function.Journal of cardiovascular development and disease · 2021Review
- Differential Spatio-Temporal Regulation of T-Box Gene Expression by microRNAs during Cardiac Development.Journal of cardiovascular development and disease · 2021Article
- Conserved Role of the Large Conductance Calcium-Activated Potassium Channel, KCirculation. Genomic and precision medicine · 2021Article
- Transcriptional Regulation of Postnatal Cardiomyocyte Maturation and Regeneration.International journal of molecular sciences · 2021Review
- In vivo identification and validation of novel potential predictors for human cardiovascular diseases.PloS one · 2021Article
- Article
- Heart Development and Regeneration in Non-mammalian Model Organisms.Frontiers in cell and developmental biology · 2020Review
- Functional Screening Identifies MicroRNA Regulators of Corin Activity and Atrial Natriuretic Peptide Biogenesis.Molecular and cellular biology · 2019Article
Corrections and comments
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Authors and funding
24 authors at 11 institutions in 4 countries.
Funding
Abstract
Unraveling the gene regulatory networks that govern development and function of the mammalian heart is critical for the rational design of therapeutic interventions in human heart disease. Using the Drosophila heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired cardiac output and altered myofibrillar architecture, and adult heart-specific interference with Cdc42 function is sufficient to cause these same defects. We also identified K(+) channels, encoded by dSUR and slowpoke, as potential effectors of the Cdc42-Tinman interaction. To determine whether a Cdc42-Nkx2-5 interaction is conserved in the mammalian heart, we examined compound heterozygous mutant mice and found conduction system and cardiac output defects. In exploring the mechanism of Nkx2-5 interaction with Cdc42, we demonstrated that mouse Cdc42 was a target of, and negatively regulated by miR-1, which itself was negatively regulated by Nkx2-5 in the mouse heart and by Tinman in the fly heart. We conclude that Cdc42 plays a conserved role in regulating heart function and is an indirect target of Tinman/Nkx2-5 via miR-1.
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Registered trials
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