Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish
Tandemly-replicated opsin genes are found in genomes of humans and zebrafish. In humans, the tandemly-replicated long wavelength-sensitive/medium wavelength-sensitive (LWS/MWS) array underlies trichromatic color vision; defects in these genes result in color blindness and X-linked retinal degenerations. The current model for regulation of tandemly replicated opsin genes states that stochastic interactions between upstream enhancer regions and gene promoters result in a preferential association with the LWS or MWS promoter. Here we provide evidence, from the LWS1/LWS2 array in zebrafish, that a trans-regulatory mechanism may instead control expression. This array is orthologous to the human LWS/MWS array but arose through an independent gene duplication event. We identified genes that were differentially expressed in zebrafish embryo eyes in response to treatment with the developmental signaling molecule retinoic acid (RA) during photoreceptor differentiation. LWS1 was significantly upregulated by this treatment, and we demonstrate that individual cone photoreceptors were induced by RA to switch expression from LWS2 to LWS1. Experimental reduction of RA signaling inhibited expression of LWS1, and endogenous RA signaling domains spatially coincided with a zone of LWS1 expression in individual cones during zebrafish retinal growth. Our findings suggest that RA signaling within the retina regulates differential expression of the LWS genes, and therefore that tandemly-replicated opsin genes may be amenable to therapeutic manipulation.
Vyšlo v časopise:
Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005483
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005483
Souhrn
Tandemly-replicated opsin genes are found in genomes of humans and zebrafish. In humans, the tandemly-replicated long wavelength-sensitive/medium wavelength-sensitive (LWS/MWS) array underlies trichromatic color vision; defects in these genes result in color blindness and X-linked retinal degenerations. The current model for regulation of tandemly replicated opsin genes states that stochastic interactions between upstream enhancer regions and gene promoters result in a preferential association with the LWS or MWS promoter. Here we provide evidence, from the LWS1/LWS2 array in zebrafish, that a trans-regulatory mechanism may instead control expression. This array is orthologous to the human LWS/MWS array but arose through an independent gene duplication event. We identified genes that were differentially expressed in zebrafish embryo eyes in response to treatment with the developmental signaling molecule retinoic acid (RA) during photoreceptor differentiation. LWS1 was significantly upregulated by this treatment, and we demonstrate that individual cone photoreceptors were induced by RA to switch expression from LWS2 to LWS1. Experimental reduction of RA signaling inhibited expression of LWS1, and endogenous RA signaling domains spatially coincided with a zone of LWS1 expression in individual cones during zebrafish retinal growth. Our findings suggest that RA signaling within the retina regulates differential expression of the LWS genes, and therefore that tandemly-replicated opsin genes may be amenable to therapeutic manipulation.
Zdroje
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Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
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