| Dhrs3a regulates retinoic acid biosynthesis through a feedback inhibition mechanism. | |
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MedLine Citation:
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PMID: 19874812 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Retinoic acid (RA) is an important developmental signaling molecule responsible for the patterning of multiple vertebrate tissues. RA is also a potent teratogen, causing multi-organ birth defects in humans. Endogenous RA levels must therefore be tightly controlled in the developing embryo. We used a microarray approach to identify genes that function as negative feedback regulators of retinoic acid signaling. We screened for genes expressed in early somite-stage embryos that respond oppositely to treatment with RA versus RA antagonists and validated them by RNA in situ hybridization. Focusing on genes known to be involved in RA metabolism, we determined that dhrs3a, which encodes a member of the short-chain dehydrogenase/reductase protein family, is both RA dependent and strongly RA inducible. Dhrs3a is known to catalyze the reduction of the RA precursor all-trans retinaldehyde to vitamin A; however, a developmental function has not been demonstrated. Using morpholino knockdown and mRNA over-expression, we demonstrate that Dhrs3a is required to limit RA levels in the embryo, primarily within the central nervous system. Dhrs3a is thus an RA-induced feedback inhibitor of RA biosynthesis. We conclude that retinaldehyde availability is an important level at which RA biosynthesis is regulated in vertebrate embryos. |
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Authors:
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L Feng; R E Hernandez; J S Waxman; D Yelon; C B Moens |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-10-27 |
Journal Detail:
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Title: Developmental biology Volume: 338 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-27 Completed Date: 2010-02-25 Revised Date: 2013-05-31 |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1-14 Citation Subset: IM |
Affiliation:
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Division of Basic Science and HHMI, Fred Hutchinson Cancer Research Center, B2-152, 1100 Fairview Ave. N, Seattle, WA 98109, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alcohol Oxidoreductases
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genetics,
metabolism* Animals Body Patterning / drug effects Embryo, Nonmammalian / cytology, drug effects, enzymology Feedback, Physiological* / drug effects Gene Expression Regulation, Developmental / drug effects Gene Knockdown Techniques Nervous System / drug effects, enzymology Neurons / cytology, drug effects, enzymology Oligonucleotide Array Sequence Analysis RNA / genetics Reproducibility of Results Retinal Dehydrogenase / genetics, metabolism Signal Transduction / drug effects Tretinoin / metabolism*, pharmacology Zebrafish Proteins / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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F32 HL083591-02/HL/NHLBI NIH HHS; F32HL083591/HL/NHLBI NIH HHS; HD37909/HD/NICHD NIH HHS; K99 HL091126-02/HL/NHLBI NIH HHS; K99HL091126/HL/NHLBI NIH HHS; R00 HL091126-06/HL/NHLBI NIH HHS; R01 HD037909-05/HD/NICHD NIH HHS; R01 HL069594/HL/NHLBI NIH HHS; R01 HL069594-08/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Zebrafish Proteins; 302-79-4/Tretinoin; 63231-63-0/RNA; EC 1.1.-/Alcohol Oxidoreductases; EC 1.1.-/Dhrs3a protein, zebrafish; EC 1.2.1.36/Retinal Dehydrogenase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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