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James M Fadool, Mailin Sotolongo-Lopez; Genetic Analysis of Photoreceptor Specification in Zebrafish Provides a Model of Rod and Cone Variation Among Vertebrates.. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
Detailed phylogenetic and functional analyses of opsins provide a foundation for the evolution of the vertebrate visual system and adaptation to different lighting environments. Lacking is knowledge of changes in a gene regulatory network that underlie the diversification of cone subtypes and the variation in the ratio of rods and cones in diurnal and nocturnal species. Taking advantage of the photoreceptor cell patterning in the cone-dominated larval zebrafish retina, we investigated potential gene interactions regulating photoreceptor variation.
Mutations affecting photoreceptor development were studied in combination or with gene knock-down approaches. Photoreceptor identity and spatial patterning were identified by confocal imaging of transgenic reporter gene expression and immunolabeling. Putative cis-regulatory elements were identified by genomic sequence alignments.
Previously, in a third generation screen, we showed that mutations of tbx2b result in an increased number and uniform distribution of rods and reduced number of UV cones; and that a hypomorphic allele of six7 results in a nearly identical rod phenotype with no evidence of change in the cones. We show here that hypomorphic alleles of six7 and tbx2b are additive in their effects upon the number of rods. In zebrafish larvae, cones outnumber rods 20:1. In double mutants, the rods account for approximately 40% of the photoreceptors. Genomic sequence analysis identified putative cis-regulatory modules in the hypomorphic alleles that may underlie the alterations. Furthermore, TALEN-generated loss-of-function alleles of six7 show death of the green cone precursors, a phototreceptor subtype not found in the mammalian retina. Lastly, gene knockdown approaches suggest epistatic interactions drive further changes in rod and cone ratios.
Based upon these data, we propose that changes in the photoreceptor gene-regulatory network are a driving force for variation in rod and cone numbers across species. The analysis show additive changes and potential epistatic interactions between genes regulating photoreceptor cell fate and survival in zebrafish. Our study indicates the potential of a small number of genotypic changes in a gene regulatory network provide substantive variation in photoreceptor phenotype and could make available selective advantage for nocturnal adaptations.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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