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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-12-23
pubmed:abstractText
Vax2 is an eye-specific homeobox gene, the inactivation of which in mouse leads to alterations in the establishment of a proper dorsoventral eye axis during embryonic development. To dissect the molecular pathways in which Vax2 is involved, we performed a transcriptome analysis of Vax2(-/-) mice throughout the main stages of eye development. We found that some of the enzymes involved in retinoic acid (RA) metabolism in the eye show significant variations of their expression levels in mutant mice. In particular, we detected an expansion of the expression domains of the RA-catabolizing enzymes Cyp26a1 and Cyp26c1, and a downregulation of the RA-synthesizing enzyme Raldh3. These changes determine a significant expansion of the RA-free zone towards the ventral part of the eye. At postnatal stages of eye development, Vax2 inactivation led to alterations of the regional expression of the cone photoreceptor genes Opn1sw (S-Opsin) and Opn1mw (M-Opsin), which were significantly rescued after RA administration. We confirmed the above described alterations of gene expression in the Oryzias latipes (medaka fish) model system using both Vax2 gain- and loss-of-function assays. Finally, a detailed morphological and functional analysis of the adult retina in mutant mice revealed that Vax2 is necessary for intraretinal pathfinding of retinal ganglion cells in mammals. These data demonstrate for the first time that Vax2 is both necessary and sufficient for the control of intraretinal RA metabolism, which in turn contributes to the appropriate expression of cone opsins in the vertebrate eye.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1477-9129
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
138
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
261-71
pubmed:meshHeading
pubmed-meshheading:21148184-Animals, pubmed-meshheading:21148184-Animals, Genetically Modified, pubmed-meshheading:21148184-Cytochrome P-450 Enzyme System, pubmed-meshheading:21148184-Eye, pubmed-meshheading:21148184-Female, pubmed-meshheading:21148184-Gene Expression Profiling, pubmed-meshheading:21148184-Gene Expression Regulation, Developmental, pubmed-meshheading:21148184-Homeodomain Proteins, pubmed-meshheading:21148184-In Situ Hybridization, pubmed-meshheading:21148184-Male, pubmed-meshheading:21148184-Mice, pubmed-meshheading:21148184-Mice, Knockout, pubmed-meshheading:21148184-Mice, Transgenic, pubmed-meshheading:21148184-Opsins, pubmed-meshheading:21148184-Oryzias, pubmed-meshheading:21148184-Pregnancy, pubmed-meshheading:21148184-Retinal Cone Photoreceptor Cells, pubmed-meshheading:21148184-Rod Opsins, pubmed-meshheading:21148184-Tretinoin
pubmed:year
2011
pubmed:articleTitle
Vax2 regulates retinoic acid distribution and cone opsin expression in the vertebrate eye.
pubmed:affiliation
Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't