Linked Life Data

15358764

Source:http://linkedlifedata.com/resource/pubmed/id/15358764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2004-11-25
pubmed:abstractText
Mutations in the APC (adenomatous polyposis coli) tumor suppressor gene cause uncontrolled proliferation and impaired differentiation of intestinal epithelial cells. Recent studies indicate that human colon adenomas and carcinomas lack retinol dehydrogenases (RDHs) and that APC regulates the expression of human RDHL. These data suggest a model wherein APC controls enterocyte differentiation by controlling retinoic acid production. However, the importance of APC and retinoic acid in mediating control of normal enterocyte development and differentiation remains unclear. To examine the relationship between APC and retinoic acid biosynthesis in normal enterocytes, we have identified two novel zebrafish retinol dehydrogenases, termed zRDHA and zRDHB, that show strong expression within the gut of developing zebrafish embryos. Morpholino knockdown of either APC or zRDHB in zebrafish embryos resulted in defects in structures known to require retinoic acid. These defects included cardiac abnormalities, pericardial edema, failed jaw and pectoral fin development, and the absence of differentiated endocrine and exocrine pancreas. In addition, APC or zRDHB morphant fish developed intestines that lacked columnar epithelial cells and failed to express the differentiation marker intestinal fatty acid-binding protein. Treatment of either APC or zRDHB morphant embryos with retinoic acid rescued the defective phenotypes. Downstream of retinoic acid production, we identified hoxc8 as a retinoic acid-induced gene that, when ectopically expressed, rescued phenotypes of APC- and zRDHB-deficient zebrafish. Our data establish a genetic link supporting a critical role for retinoic acid downstream of APC and confirm the importance of retinoic acid in enterocyte differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51581-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15358764-Adenomatous Polyposis Coli Protein, pubmed-meshheading:15358764-Alcohol Oxidoreductases, pubmed-meshheading:15358764-Amino Acid Sequence, pubmed-meshheading:15358764-Animals, pubmed-meshheading:15358764-Animals, Genetically Modified, pubmed-meshheading:15358764-Cell Differentiation, pubmed-meshheading:15358764-Chromatography, High Pressure Liquid, pubmed-meshheading:15358764-DNA, Complementary, pubmed-meshheading:15358764-Enterocytes, pubmed-meshheading:15358764-Gene Expression Regulation, Developmental, pubmed-meshheading:15358764-Homeodomain Proteins, pubmed-meshheading:15358764-Intestines, pubmed-meshheading:15358764-Molecular Sequence Data, pubmed-meshheading:15358764-Phenotype, pubmed-meshheading:15358764-Phylogeny, pubmed-meshheading:15358764-RNA, pubmed-meshheading:15358764-RNA, Messenger, pubmed-meshheading:15358764-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15358764-Sequence Homology, Amino Acid, pubmed-meshheading:15358764-Tretinoin, pubmed-meshheading:15358764-Zebrafish, pubmed-meshheading:15358764-Zebrafish Proteins
pubmed:year
2004
pubmed:articleTitle
Adenomatous polyposis coli control of retinoic acid biosynthesis is critical for zebrafish intestinal development and differentiation.
pubmed:affiliation
Department of Oncological Sciences, University of Utah, Salt Lake City 84112, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't