ArticlePLoS genetics2013
Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
- Pilot: Wnt signaling controlsmicroPublication biology · 2026Article
- Tbx1-dependent and independent pathways promote six gene expression downstream of retinoic acid signaling to determine cardiomyocyte number in zebrafish.Developmental biology · 2025Article
- A Foxf1-Wnt-Nr2f1 cascade promotes atrial cardiomyocyte differentiation in zebrafish.PLoS genetics · 2024Article
- A Foxf1-Wnt-Nr2f1 cascade promotes atrial cardiomyocyte differentiation in zebrafish.bioRxiv : the preprint server for biology · 2024Article
- Zebrafish as a Model to Study Retinoic Acid Signaling in Development and Disease.Biomedicines · 2023Review
- ALDH1A2-related disorder: A new genetic syndrome due to alteration of the retinoic acid pathway.American journal of medical genetics. Part A · 2023Article
- Stx4 is required to regulate cardiomyocyte CaHGG advances · 2022Article
- Dissecting mechanisms of chamber-specific cardiac differentiation and its perturbation following retinoic acid exposure.Development (Cambridge, England) · 2022Article
- Mechanisms of Feedback Regulation of Vitamin A Metabolism.Nutrients · 2022Review
- Patterning of vertebrate cardiac progenitor fields by retinoic acid signaling.Genesis (New York, N.Y. : 2000) · 2021Review
- Ccdc103 promotes myeloid cell proliferation and migration independent of motile cilia.Disease models & mechanisms · 2021Article
- Atrial and Sinoatrial Node Development in the Zebrafish Heart.Journal of cardiovascular development and disease · 2021Review
- Retinoic Acid Fluctuation Activates an Uneven, Direction-Dependent Network-Wide Robustness Response in Early Embryogenesis.Frontiers in cell and developmental biology · 2021Article
- Mesoderm patterning by a dynamic gradient of retinoic acid signalling.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Review
- Variations in maternal vitamin A intake modifies phenotypes in a mouse model of 22q11.2 deletion syndrome.Birth defects research · 2020Article
- Mutation of amphioxus Pdx and Cdx demonstrates conserved roles for ParaHox genes in gut, anus and tail patterning.BMC biology · 2020Article
- Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes.Journal of developmental biology · 2020Review
- Pbx4 limits heart size and fosters arch artery formation by partitioning second heart field progenitors and restricting proliferation.Development (Cambridge, England) · 2020Article
- Epicardium in Heart Development.Cold Spring Harbor perspectives in biology · 2020Review
- Identifying vitamin A signaling by visualizing gene and protein activity, and by quantification of vitamin A metabolites.Methods in enzymology · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA) signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1), a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM) specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA.
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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.