ArticlePLoS genetics2019
Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Pooled it
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- Osr1 orchestrates posterior second heart field cell migration for outflow tract formation.Communications biology · 2025Article
- Loss-of-function variants in ciliary genes confer high risk for tetralogy of Fallot.Science advances · 2025Article
- Gata6 functions in zebrafish endoderm to regulate late differentiating arterial pole cardiogenesis.Development (Cambridge, England) · 2024Article
- Molecular Pathways and Animal Models of Tetralogy of Fallot and Double Outlet Right Ventricle.Advances in experimental medicine and biology · 2024Review
- RNA binding proteins in cardiovascular development and disease.Current topics in developmental biology · 2024Article
- Single-cell profiling of the developing embryonic heart in Drosophila.Development (Cambridge, England) · 2023Article
- Genetic Alterations of Transcription Factors and Signaling Molecules Involved in the Development of Congenital Heart Defects-A Narrative Review.Children (Basel, Switzerland) · 2023Review
- Transgenic Mouse Models to Study the Development and Maintenance of the Adrenal Cortex.International journal of molecular sciences · 2022Review
- Towards Understanding the Gene-Specific Roles of GATA Factors in Heart Development: Does GATA4 Lead the Way?International journal of molecular sciences · 2022Review
- GATA4/5/6 family transcription factors are conserved determinants of cardiac versus pharyngeal mesoderm fate.Science advances · 2022Article
- Understanding Heart Field Progenitor Cells for Modeling Congenital Heart Diseases.Current cardiology reports · 2021Review
- The Classification of VACTERL Association into 3 Groups According to the Limb Defect.Plastic and reconstructive surgery. Global open · 2021Article
- Mutations in RNA Methyltransferase GeneFrontiers in cell and developmental biology · 2021Article
- LRP2 controls sonic hedgehog-dependent differentiation of cardiac progenitor cells during outflow tract formation.Human molecular genetics · 2020Article
- Genetics of Congenital Heart Disease.Biomolecules · 2019Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Dominant mutations of Gata4, an essential cardiogenic transcription factor (TF), were known to cause outflow tract (OFT) defects in both human and mouse, but the underlying molecular mechanism was not clear. In this study, Gata4 haploinsufficiency in mice was found to result in OFT defects including double outlet right ventricle (DORV) and ventricular septum defects (VSDs). Gata4 was shown to be required for Hedgehog (Hh)-receiving progenitors within the second heart field (SHF) for normal OFT alignment. Restored cell proliferation in the SHF by knocking-down Pten failed to rescue OFT defects, suggesting that additional cell events under Gata4 regulation is important. SHF Hh-receiving cells failed to migrate properly into the proximal OFT cushion, which is associated with abnormal EMT and cell proliferation in Gata4 haploinsufficiency. The genetic interaction of Hh signaling and Gata4 is further demonstrated to be important for OFT development. Gata4 and Smo double heterozygotes displayed more severe OFT abnormalities including persistent truncus arteriosus (PTA). Restoration of Hedgehog signaling renormalized SHF cell proliferation and migration, and rescued OFT defects in Gata4 haploinsufficiency. In addition, there was enhanced Gata6 expression in the SHF of the Gata4 heterozygotes. The Gata4-responsive repressive sites were identified within 1kbp upstream of the transcription start site of Gata6 by both ChIP-qPCR and luciferase reporter assay. These results suggested a SHF regulatory network comprising of Gata4, Gata6 and Hh-signaling for OFT development.
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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.