Document Detail

Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development.
MedLine Citation:
PMID:  16938888     Owner:  NLM     Status:  MEDLINE    
Congenital hypertrophy/hyperplasia of the retinal pigmented epithelium is an ocular lesion found in patients harboring mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. We report that Apc-deficient zebrafish display developmental abnormalities of both the lens and retina. Injection of dominant-negative Lef reduced Wnt signaling in the lens but did not rescue retinal differentiation defects. In contrast, treatment of apc mutants with all-trans retinoic acid rescued retinal differentiation defects but had no apparent effect on the lens. We identified Rdh5 as a retina-specific retinol dehydrogenase controlled by APC. Morpholino knockdown of Rdh5 phenocopied the apc mutant retinal differentiation defects and was rescued by treatment with exogenous all-trans retinoic acid. Microarray analyses of apc mutants and Rdh5 morphants revealed a profound overlap in the transcriptional profile of these embryos. These findings support a model wherein Apc serves a dual role in regulating Wnt and retinoic acid signaling within the eye and suggest retinoic acid deficiency as an explanation for APC mutation-associated retinal defects such as congenital hypertrophy/hyperplasia of the retinal pigmented epithelium.
Lincoln D Nadauld; Stephanie Chidester; Dawne N Shelton; Kunal Rai; Talmage Broadbent; Imelda T Sandoval; Peter W Peterson; Elizabeth J Manos; Chris M Ireland; H Joseph Yost; David A Jones
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-08-28
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  103     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-06     Completed Date:  2006-10-19     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13409-14     Citation Subset:  IM    
Department of Oncological Sciences and Medicinal Chemistry and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
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MeSH Terms
Adenomatous Polyposis Coli Protein / deficiency,  genetics,  metabolism*
Eye / drug effects,  embryology*
Gene Expression Regulation, Developmental
Molecular Sequence Data
Oligonucleotides, Antisense / pharmacology
Tretinoin / metabolism*,  pharmacology
Wnt Proteins / metabolism*
Zebrafish / embryology*,  genetics
Reg. No./Substance:
0/Adenomatous Polyposis Coli Protein; 0/Oligonucleotides, Antisense; 0/Wnt Proteins; 302-79-4/Tretinoin

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