ArticleCell reports2014
Hand2 is an essential regulator for two Notch-dependent functions within the embryonic endocardium.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
- Endocardial transcription factor HAND2 orchestrates hypoxic and TGF-β signaling to modulate coronary artery formation.The Journal of clinical investigation · 2026Article
- A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects.Nature cardiovascular research · 2026Article
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Hand1 gene replacement with Hand2 reveals overlap in function with unique occurrence of omphalocele and heart defects.Development (Cambridge, England) · 2025Article
- Sodium Fluoride Exposure Induces Developmental Toxicity and Cardiotoxicity in Zebrafish Embryos.Biological trace element research · 2025Article
- Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects.Journal of the American Heart Association · 2025Article
- The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024Review
- Genetic and phenotypic architecture of human myocardial trabeculation.Nature cardiovascular research · 2024Article
- β1 integrins regulate cellular behaviour and cardiomyocyte organization during ventricular wall formation.Cardiovascular research · 2024Article
- Epigenetic determinants and non-myocardial signaling pathways contributing to heart growth and regeneration.Pharmacology & therapeutics · 2024Review
- Identification and characterization of Hand2 upstream genomic enhancers active in developing stomach and limbs.Developmental dynamics : an official publication of the American Association of Anatomists · 2024Article
- Distinct HAND2/HAND2-AS1 Expression Levels May Fine-Tune Mesenchymal and Epithelial Cell Plasticity of Human Mesenchymal Stem Cells.International journal of molecular sciences · 2023Article
- Single cell evaluation of endocardial Hand2 gene regulatory networks reveals HAND2-dependent pathways that impact cardiac morphogenesis.Development (Cambridge, England) · 2023Article
- Generation of a recombinant version of a biologically active cell-permeant human HAND2 transcription factor from E. coli.Scientific reports · 2022Article
- The adult heart requires baseline expression of the transcription factor Hand2 to withstand right ventricular pressure overload.Cardiovascular research · 2022Article
- Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity-a narrative review.Cardiovascular diagnosis and therapy · 2022Review
- Neonatal Deletion ofJournal of cardiovascular development and disease · 2022Article
- Delving into the Molecular World of Single Ventricle Congenital Heart Disease.Current cardiology reports · 2022Review
- Endocardial Regulation of Cardiac Development.Journal of cardiovascular development and disease · 2022Review
- Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish.American journal of physiology. Heart and circulatory physiology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
The basic-helix-loop-helix (bHLH) transcription factor Hand2 plays critical roles during cardiac morphogenesis via expression and function within myocardial, neural crest, and epicardial cell populations. Here, we show that Hand2 plays two essential Notch-dependent roles within the endocardium. Endocardial ablation of Hand2 results in failure to develop a patent tricuspid valve, intraventricular septum defects, and hypotrabeculated ventricles, which collectively resemble the human congenital defect tricuspid atresia. We show endocardial Hand2 to be an integral downstream component of a Notch endocardium-to-myocardium signaling pathway and a direct transcriptional regulator of Neuregulin1. Additionally, Hand2 participates in endocardium-to-endocardium-based cell signaling, with Hand2 mutant hearts displaying an increased density of coronary lumens. Molecular analyses further reveal dysregulation of several crucial components of Vegf signaling, including VegfA, VegfR2, Nrp1, and VegfR3. Thus, Hand2 functions as a crucial downstream transcriptional effector of endocardial Notch signaling during both cardiogenesis and coronary vasculogenesis.
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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.