Document Detail

Retinoic acid-induced thymic abnormalities in the mouse are associated with altered pharyngeal morphology, thymocyte maturation defects, and altered expression of Hoxa3 and Pax1.
MedLine Citation:
PMID:  9894676     Owner:  NLM     Status:  MEDLINE    
Exogenous retinoic acid is teratogenic in animals and man, causing a spectrum of abnormalities termed retinoic acid embryopathy. Using a mouse model of retinoic acid embryopathy, our results show that exposure to all-trans retinoic acid (RA) on gestational day (gd) 9 results in thymic ectopia, hypoplasia, and thymocyte maturational defects. Immunohistochemical and flow cytometric analyses showed aberrant expression of stromal and thymocyte markers, and abnormalities in thymocyte development. RNA in situ hybridization for the transcription factors Hoxa3 and Pax1 was used to investigate the basis of this defect. Hoxa3 and Pax1 have been shown to be required for normal thymus development, and are normally expressed in the cells of the third pharyngeal pouch and third and fourth pharyngeal arches, involved in thymus organogenesis RA-exposed embryos showed an increased level of Hoxa3 expression in the neural tube and caudal pharyngeal arches as soon as 6 hr after exposure. The Pax1 expression pattern, in conjunction with analysis of the external pharyngeal morphology, showed that the development and structure of the third pharyngeal pouch and cleft were disrupted, resulting in a reduced third pharyngeal arch and/or fusion of the third and fourth arches. Changes in the expression of cellular retinoic acid binding protein (CRABP) and in the morphology of the cranial ganglia were consistent with altered neural crest cell migration from the caudal hindbrain after RA exposure. Together, our findings suggest that the teratogenic effects of RA on thymus development include changes in both the cranial neural crest and pharyngeal endoderm that contribute to thymus development. Further, the observed defects in thymus development may be mediated by RA-induced alterations in the expression of Hoxa3.
G B Mulder; N Manley; L Maggio-Price
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Teratology     Volume:  58     ISSN:  0040-3709     ISO Abbreviation:  Teratology     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-03-24     Completed Date:  1999-03-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0153257     Medline TA:  Teratology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  263-75     Citation Subset:  IM    
University Laboratory Animal Resources, University of California at Irvine 92697-1310, USA.
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MeSH Terms
Branchial Region / abnormalities,  metabolism
DNA-Binding Proteins / metabolism*
Flow Cytometry
Gene Expression Regulation, Developmental
Homeodomain Proteins*
In Situ Hybridization
Mice, Inbred C57BL
Neural Crest / abnormalities,  metabolism
Paired Box Transcription Factors
Rhombencephalon / drug effects,  embryology
Teratogens / toxicity*
Thymus Gland / abnormalities*,  embryology
Transcription Factors / metabolism*
Tretinoin / metabolism,  toxicity*
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/HOX3A protein, Felis catus; 0/Homeodomain Proteins; 0/Paired Box Transcription Factors; 0/Teratogens; 0/Transcription Factors; 142661-96-9/PAX1 transcription factor; 302-79-4/Tretinoin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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