Vax2 regulates retinoic acid distribution and cone opsin expression in the vertebrate eye

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 thr...

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Veröffentlicht in:Development (Cambridge) 2011-01, Vol.138 (2), p.261-271
Hauptverfasser: Alfano, Giovanna, Conte, Ivan, Caramico, Tiziana, Avellino, Raffaella, Arnò, Benedetta, Pizzo, Maria Teresa, Tanimoto, Naoyuki, Beck, Susanne C, Huber, Gesine, Dollé, Pascal, Seeliger, Mathias W, Banfi, Sandro
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container_end_page 271
container_issue 2
container_start_page 261
container_title Development (Cambridge)
container_volume 138
creator Alfano, Giovanna
Conte, Ivan
Caramico, Tiziana
Avellino, Raffaella
Arnò, Benedetta
Pizzo, Maria Teresa
Tanimoto, Naoyuki
Beck, Susanne C
Huber, Gesine
Dollé, Pascal
Seeliger, Mathias W
Banfi, Sandro
description 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.
doi_str_mv 10.1242/dev.051037
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subjects Animals
Animals, Genetically Modified
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Cytochrome P450 Family 26
Eye - growth & development
Eye - metabolism
Female
Gene Expression Profiling
Gene Expression Regulation, Developmental
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
In Situ Hybridization
Male
Mice
Mice, Knockout
Mice, Transgenic
Opsins - genetics
Opsins - metabolism
Oryzias - genetics
Oryzias - growth & development
Oryzias - metabolism
Oryzias latipes
Pregnancy
Retinal Cone Photoreceptor Cells - metabolism
Retinoic Acid 4-Hydroxylase
Rod Opsins - genetics
Rod Opsins - metabolism
Tretinoin - metabolism
title Vax2 regulates retinoic acid distribution and cone opsin expression in the vertebrate eye
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