Document Detail

Growth differentiation factor 11 signaling controls retinoic acid activity for axial vertebral development.
MedLine Citation:
PMID:  20801112     Owner:  NLM     Status:  MEDLINE    
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.
Young Jae Lee; Alexandra McPherron; Susan Choe; Yasuo Sakai; Roshantha A Chandraratna; Se-Jin Lee; S Paul Oh
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-27
Journal Detail:
Title:  Developmental biology     Volume:  347     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-05     Completed Date:  2010-11-26     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  195-203     Citation Subset:  IM    
Copyright Information:
Copyright © 2010. Published by Elsevier Inc.
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MeSH Terms
Activin Receptors, Type II / metabolism
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
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
Wnt3 Protein
Grant Support
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/Gdf11 protein, mouse; 0/Growth Differentiation Factors; 0/Wnt Proteins; 0/Wnt3 Protein; 5688UTC01R/Tretinoin; 9035-51-2/Cytochrome P-450 Enzyme System; EC acid 4-hydroxylase; EC Receptors, Type II; EC receptor type II-B

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