ArticleProceedings of the National Academy of Sciences of the United States of America2008
Retinoic acid deficiency alters second heart field formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 1 of them a synthesis that pooled it.
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Who cites it
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
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- Impact of Cannabis and Cannabis Legalization on US Atrial Septal Defect Rates.Journal of xenobiotics · 2026Article
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- Tbx1-dependent and independent pathways promote six gene expression downstream of retinoic acid signaling to determine cardiomyocyte number in zebrafish.Developmental biology · 2025Article
- Retinoic acid promotes second heart field addition and regulates ventral aorta patterning in zebrafish.Developmental biology · 2025Article
- A retinoic acid:YAP1 signaling axis controls atrial lineage commitment.Cell reports · 2025Article
- Region- and Cell-type-Resolved Multiomic Atlas of the Heart.Molecular & cellular proteomics : MCP · 2025Article
- Retinoic acid signaling and metabolism in heart failure.American journal of physiology. Heart and circulatory physiology · 2025Review
- Early retinoic acid signaling organizes the body axis and defines domains for the forelimb and eye.Current topics in developmental biology · 2025Review
- The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024Review
- A Foxf1-Wnt-Nr2f1 cascade promotes atrial cardiomyocyte differentiation in zebrafish.PLoS genetics · 2024Article
- Epigenetic determinants and non-myocardial signaling pathways contributing to heart growth and regeneration.Pharmacology & therapeutics · 2024Review
- A Foxf1-Wnt-Nr2f1 cascade promotes atrial cardiomyocyte differentiation in zebrafish.bioRxiv : the preprint server for biology · 2024Article
- State-of-the-Art Differentiation Protocols for Patient-Derived Cardiac Pacemaker Cells.International journal of molecular sciences · 2024Review
- Differentiation of Pluripotent Stem Cells for Disease Modeling: Learning from Heart Development.Pharmaceuticals (Basel, Switzerland) · 2024Review
- CD151 expression marks atrial- and ventricular- differentiation from human induced pluripotent stem cells.Communications biology · 2024Article
- The Tbx20-TLE interaction is essential for the maintenance of the second heart field.Development (Cambridge, England) · 2023Article
- The second heart field: the first 20 years.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Retinoic acid (RA), the active derivative of vitamin A, has been implicated in various steps of cardiovascular development. The retinaldehyde dehydrogenase 2 (RALDH2) enzyme catalyzes the second oxidative step in RA biosynthesis and its loss of function creates a severe embryonic RA deficiency. Raldh2(-/-) knockout embryos fail to undergo heart looping and have impaired atrial and sinus venosus development. To understand the mechanism(s) producing these changes, we examined the contribution of the second heart field (SHF) to pharyngeal mesoderm, atria, and outflow tract in Raldh2(-/-) embryos. RA deficiency alters SHF gene expression in two ways. First, Raldh2(-/-) embryos exhibited a posterior expansion of anterior markers of the SHF, including Tbx1, Fgf8, and the Mlc1v-nlacZ-24/Fgf10 reporter transgene as well as of Islet1. This occurred at early somite stages, when cardiac defects became irreversible in an avian vitamin A-deficiency model, indicating that endogenous RA is required to restrict the SHF posteriorly. Explant studies showed that this expanded progenitor population cannot differentiate properly. Second, RA up-regulated cardiac Bmp expression levels at the looping stage. The contribution of the SHF to both inflow and outflow poles was perturbed under RA deficiency, creating a disorganization of the heart tube. We also investigated genetic cross-talk between Nkx2.5 and RA signaling by generating double mutant mice. Strikingly, Nkx2.5 deficiency was able to rescue molecular defects in the posterior region of the Raldh2(-/-) mutant heart, in a gene dosage-dependent manner.
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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.