ArticleBasic research in cardiology2013
Islet1 is a direct transcriptional target of the homeodomain transcription factor Shox2 and rescues the Shox2-mediated bradycardia.
Article in Basic research in cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 75 citations in OpenAlex.
- Nr2f1a and Isl1 repress acquisition of epicardial identity in venous atrial cardiomyocytes.Development (Cambridge, England) · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Linking shox/shox2 deficiency with fgfr3 gain-of-function and natriuretic peptides.Frontiers in endocrinology · 2026Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Uric Acid Disrupts Heart Development in Zebrafish by Inhibiting the Wnt Signaling Pathway.Cardiovascular toxicology · 2025Article
- The Neglected Internodal Tract-A Cardiac Conduction System Structure Homologous to the Development and Regulation of the Sinoatrial Node.Reviews in cardiovascular medicine · 2025Review
- Comparative Analyses Reveal Conserved and Modified Steps in the Testis Descent and Scrotum Development in Mouse and Opossum.Cells, tissues, organs · 2025Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells.International journal of molecular sciences · 2024Review
- Development of the Cardiac Conduction System.Advances in experimental medicine and biology · 2024Article
- Advances and Prospects in Understanding Vertebrate Cardiac Conduction System, Pacemaker Cell, and Cardiac Muscle Development: Toward Novel Biological Therapies.Muscles (Basel, Switzerland) · 2023Review
- Nr2f1a maintains atrialeLife · 2023Article
- Comparative Study of Transcriptome in the Hearts Isolated from Mice, Rats, and Humans.Biomolecules · 2022Article
- Preferential Expression of CaBiomolecules · 2022Article
- Retinoic acid signaling in heart development: Application in the differentiation of cardiovascular lineages from human pluripotent stem cells.Stem cell reports · 2021Review
- Atrial and Sinoatrial Node Development in the Zebrafish Heart.Journal of cardiovascular development and disease · 2021Review
- Genetic Complexity of Sinoatrial Node Dysfunction.Frontiers in genetics · 2021Review
- Identification and Tissue-Specific Characterization of Novel SHOX-Regulated Genes in Zebrafish Highlights SOX Family Members Among Other Genes.Frontiers in genetics · 2021Article
- Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer.Circulation research · 2020Article
- Development of the Cardiac Conduction System.Cold Spring Harbor perspectives in biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heart's rhythm is initiated and regulated by a group of specialized cells in the sinoatrial node (SAN), the primary pacemaker of the heart. Abnormalities in the development of the SAN can result in irregular heart rates (arrhythmias). Although several of the critical genes important for SAN formation have been identified, our understanding of the transcriptional network controlling SAN development remains at a relatively early stage. The homeodomain transcription factor Shox2 is involved in the specification and patterning of the SAN. While the Shox2 knockout in mice results in embryonic lethality due to severe cardiac defects including improper SAN development, Shox2 knockdown in zebrafish causes a reduced heart rate (bradycardia). In order to gain deeper insight into molecular pathways involving Shox2, we compared gene expression levels in right atria of wildtype and Shox2 (-/-) hearts using microarray experiments and identified the LIM homeodomain transcription factor Islet1 (Isl1) as one of its putative target genes. The downregulation of Isl1 expression in Shox2 (-/-) hearts was confirmed and the affected region narrowed down to the SAN by whole-mount in situ hybridization. Using luciferase reporter assays and EMSA studies, we identified two specific SHOX2 binding sites within intron 2 of the ISL1 locus. We also provide functional evidence for Isl1 as a transcriptional target of Shox2 by rescuing the Shox2-mediated bradycardia phenotype with Isl1 using zebrafish as a model system. Our findings demonstrate a novel epistatic relationship between Shox2 and Isl1 in the heart with important developmental consequences for SAN formation and heart beat.
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.