| Growth differentiation factor 11 signaling controls retinoic acid activity for axial vertebral development. | |
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MedLine Citation:
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PMID: 20801112 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mice deficient in growth differentiation factor 11 (GDF11) signaling display anterior transformation of axial vertebrae and truncation of caudal vertebrae. However, the in vivo molecular mechanisms by which GDF11 signaling regulates the development of the vertebral column have yet to be determined. We found that Gdf11 and Acvr2b mutants are sensitive to exogenous RA treatment on vertebral specification and caudal vertebral development. We show that diminished expression of Cyp26a1, a retinoic acid inactivating enzyme, and concomitant elevation of retinoic acid activity in the caudal region of Gdf11(-/-) embryos may account for this phenomenon. Reduced expression or function of Cyp26a1 enhanced anterior transformation of axial vertebrae in wild-type and Acvr2b mutants. Furthermore, a pan retinoic acid receptor antagonist (AGN193109) could lessen the anterior transformation phenotype and rescue the tail truncation phenotype of Gdf11(-/-) mice. Taken together, these results suggest that GDF11 signaling regulates development of caudal vertebrae and is involved in specification of axial vertebrae in part by maintaining Cyp26a1 expression, which represses retinoic acid activity in the caudal region of embryos during the somitogenesis stage. |
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Authors:
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Young Jae Lee; Alexandra McPherron; Susan Choe; Yasuo Sakai; Roshantha A Chandraratna; Se-Jin Lee; S Paul Oh |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-27 |
Journal Detail:
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Title: Developmental biology Volume: 347 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-05 Completed Date: 2010-11-26 Revised Date: 2011-11-01 |
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: 195-203 Citation Subset: IM |
Copyright Information:
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Copyright © 2010. Published by Elsevier Inc. |
Affiliation:
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Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL 32610, USA. leeyj@gachon.ac.kr |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Activin Receptors, Type II
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metabolism Animals Body Patterning* / drug effects, genetics Bone Morphogenetic Proteins / genetics, metabolism* Cytochrome P-450 Enzyme System / genetics, metabolism Embryo, Mammalian / drug effects, enzymology Gene Expression Regulation, Developmental / drug effects Growth Differentiation Factors / genetics, metabolism* Mesoderm / drug effects, embryology, enzymology Mice Mutation / genetics Signal Transduction* / drug effects Somites / drug effects, embryology, enzymology Spine / drug effects, embryology*, metabolism* Tail / abnormalities, drug effects Tretinoin / metabolism*, pharmacology Wnt Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AR060636/AR/NIAMS NIH HHS; HD35887/HD/NICHD NIH HHS; R01 AR060636-11A2/AR/NIAMS NIH HHS; R01 AR060636-12/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bone Morphogenetic Proteins; 0/Gdf11 protein, mouse; 0/Growth Differentiation Factors; 0/Wnt Proteins; 0/Wnt-3 protein; 302-79-4/Tretinoin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/retinoic acid 4-hydroxylase; EC 2.7.11.30/Activin Receptors, Type II; EC 2.7.11.30/activin receptor type II-B |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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