ArticleGenes & development2004
The Notch target genes Hey1 and Hey2 are required for embryonic vascular development.
Article in Genes & development, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 314 papers.
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Who cites it
314 citing papers in PubMed, 647 citations in OpenAlex.
- Ultra high-resolution gene centric genomic structural analysis of a non-syndromic congenital heart defect, Tetralogy of Fallot.PloS one · 2014Trial
- A viscoelastic suspension culture strategy modulating fusion and development in blood vessel organoids.Bioactive materials · 2026Article
- Compartment-specific regulation of stromal differentiation of the spleen in health and disease.Genes and immunity · 2026Review
- Article
- IKKβ and USP28 Regulate HEY1 Stability to Promote Cancer Stemness and Immune Evasion in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell omics uncovers novel pathological mechanisms and therapeutic targets for congenital heart diseases: insights from integrated intercellular communication analysis.Stem cell research & therapy · 2026Review
- Prdm16 Amplifies Notch Signaling and Suppresses Venous Lineage Specification to Prevent Arteriovenous Malformations During Vascular Development.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Protein networks are influenced by maternal BMI and differentiate preterm birth types.Communications medicine · 2026Article
- Single-cell RNA sequencing reveals disease associated changes in brain endothelial cells in the 5XFAD mouse.Fluids and barriers of the CNS · 2026Article
- A cell and transcriptome atlas of human arterial vasculature.Cell genomics · 2025Article
- Discovery of a pre-vein progenitor that requires VEGF/ERK inhibition to complete vein differentiation.bioRxiv : the preprint server for biology · 2025Article
- A novel Notch and WNT signaling mechanism contribute to paediatric DCM: a pathway to new therapeutics.bioRxiv : the preprint server for biology · 2025Article
- Tabula Sapiens reveals transcription factor expression, senescence effects, and sex-specific features in cell types from 28 human organs and tissues.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive multi-omics analysis uncovers potential risks of aged sperm on offspring development after short-term storage.BMC biology · 2025Article
- NOTCH Signaling Networks in Perivascular Adipose Tissue.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Feto-placental blood vessel development.Development (Cambridge, England) · 2025Review
- Multifaceted Role of Notch Signaling in Vascular Health and Diseases.Biomedicines · 2025Review
- DGCR8 haploinsufficiency leads to primate-specific RNA dysregulation and pluripotency defects.Nucleic acids research · 2025Article
- The transcriptional repressor HEY2 regulates mitochondrial oxidative respiration to maintain cardiac homeostasis.Nature communications · 2025Article
- The role of endothelial cell-pericyte interactions in vascularization and diseases.Journal of advanced research · 2025Review
254 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Delta-Notch signaling pathway plays a central role in the development of most vertebrate organs. The Hey family of bHLH transcription factors are direct targets of Notch signaling. Loss of Hey2 in the mouse leads to cardiac defects with high postnatal lethality. We have now generated a mouse Hey1 knockout that has no apparent phenotypic defect. The combined loss of Hey1 and Hey2, however, results in embryonic death after embryonic day 9.5 (E9.5) with a global lack of vascular remodeling and massive hemorrhage. Initial vasculogenesis appears unaffected, but all subsequently developing major vessels in the embryo and yolk sac are either small or absent. Furthermore, the placental labyrinth completely lacks embryonic blood vessels. Similar vascular defects are observed in Jagged1 and Notch1 knockout mice. In the latter we found Hey1 and Hey2 expression in yolk sacs to be strongly reduced. Remaining large arteries in both Notch1 and Hey1/Hey2 knockout mice fail to express the arterial endothelial markers CD44, neuropilin1, and ephrin-B2. This indicates that Hey1/Hey2 are essential transducers of Notch signals in cardiovascular development that may mediate arterial cell fate decision.
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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.