ArticlePloS one2015
Heparan Sulfate Biosynthesis Enzyme, Ext1, Contributes to Outflow Tract Development of Mouse Heart via Modulation of FGF Signaling.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Identification of a Lactylation-Related Gene Signature and Candidate Biomarkers for Dilated Cardiomyopathy.Journal of cellular and molecular medicine · 2026Article
- Heparan sulfate regulates myofibroblast heterogeneity and function to mediate niche homeostasis during alveolar morphogenesis.Nature communications · 2025Article
- Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms.Circulation. Genomic and precision medicine · 2023Article
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- Gene-Interaction-Sensitive enrichment analysis in congenital heart disease.BioData mining · 2022Article
- Cardiac Neural Crest.Cold Spring Harbor perspectives in biology · 2021Review
- The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair.Frontiers in cell and developmental biology · 2021Review
- Multiple roles of epithelial heparan sulfate in stomach morphogenesis.Journal of cell science · 2018Article
- Epithelial heparan sulfate regulates Sonic Hedgehog signaling in lung development.PLoS genetics · 2017Article
- Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity: EFFECTS ON EMBRYO SURVIVAL.The Journal of biological chemistry · 2016Article
- Roles of FGF Signals in Heart Development, Health, and Disease.Frontiers in cell and developmental biology · 2016Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycosaminoglycans are important regulators of multiple signaling pathways. As a major constituent of the heart extracellular matrix, glycosaminoglycans are implicated in cardiac morphogenesis through interactions with different signaling morphogens. Ext1 is a glycosyltransferase responsible for heparan sulfate synthesis. Here, we evaluate the function of Ext1 in heart development by analyzing Ext1 hypomorphic mutant and conditional knockout mice. Outflow tract alignment is sensitive to the dosage of Ext1. Deletion of Ext1 in the mesoderm induces a cardiac phenotype similar to that of a mutant with conditional deletion of UDP-glucose dehydrogenase, a key enzyme responsible for synthesis of all glycosaminoglycans. The outflow tract defect in conditional Ext1 knockout(Ext1f/f:Mesp1Cre) mice is attributable to the reduced contribution of second heart field and neural crest cells. Ext1 deletion leads to downregulation of FGF signaling in the pharyngeal mesoderm. Exogenous FGF8 ameliorates the defects in the outflow tract and pharyngeal explants. In addition, Ext1 expression in second heart field and neural crest cells is required for outflow tract remodeling. Our results collectively indicate that Ext1 is crucial for outflow tract formation in distinct progenitor cells, and heparan sulfate modulates FGF signaling during early heart development.
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