Abstract
The visual system of a particular species is highly adapted to convey detailed ecological and behavioral information essential for survival. The consequences of structural mutations of opsins upon spectral sensitivity and environmental adaptation have been studied in great detail, but lacking is knowledge of the potential influence of alterations in gene regulatory networks upon the diversity of cone subtypes and the variation in the ratio of rods and cones observed in numerous diurnal and nocturnal species. Exploiting photoreceptor patterning in cone-dominated zebrafish, we uncovered two independent mechanisms by which the sine oculis homeobox homolog 7 (six7) regulates photoreceptor development. In a genetic screen, we isolated the lots-of-rods-junior (ljrp23ahub) mutation that resulted in an increased number and uniform distribution of rods in otherwise normal appearing larvae. Sequence analysis, genome editing using TALENs and knockdown strategies confirm ljrp23ahub as a hypomorphic allele of six7, a teleost orthologue of six3, with known roles in forebrain patterning and expression of opsins. Based on the lack of predicted protein-coding changes and a deletion of a conserved element upstream of the transcription start site, a cis-regulatory mutation is proposed as the basis of the reduced expression of six7 in ljrp23ahub. Comparison of the phenotypes of the hypomorphic and knock-out alleles provides evidence of two independent roles in photoreceptor development. EdU and PH3 labeling show that the increase in rod number is associated with extended mitosis of photoreceptor progenitors, and TUNEL suggests that the lack of green-sensitive cones is the result of cell death of the cone precursor. These data add six7 to the small but growing list of essential genes for specification and patterning of photoreceptors in non-mammalian vertebrates, and highlight alterations in transcriptional regulation as a potential source of photoreceptor variation across species.
Highlights
Sensory systems provide a critical link for an animal to its ever changing and complex environment
Retinas of most mammals are better adapted for dim light conditions with rods vastly outnumbering the sparse and less diverse cone subtypes
Our understanding of photoreceptor development largely based on findings from mammalian models fails to explain the tremendous diversity of cone subtypes and variation of rod and cone numbers across the majority of vertebrate species
Summary
Sensory systems provide a critical link for an animal to its ever changing and complex environment. Representatives from most classes of extant vertebrates possess a duplex retina with two distinct types of photoreceptors: rods, which are highly sensitive to light, mediate scotopic or dim light vision; and cones, which function under daylight or bright light conditions, are responsible for color vision. The spectral sensitivity of cones is dependent upon the expression of one of four different visual pigments or opsins with peak sensitivity to ultraviolet or violet (SWS1), blue (SWS2), green (RH2), or red (LWS) wavelengths of light. Detailed phylogenetic and functional analyses of structural mutations affecting spectral sensitivity provide much insight about the evolution of the visual system and adaptation to different lighting environments [1], [2], [3], [4], [5], [6]. The molecular mechanisms leading to the major evolutionary changes in photoreceptor composition among vertebrate species remain unclear
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