Six6 and Six7 coordinately regulate expression of middle-wavelength opsins in zebrafish

Ogawa, Y., Shiraki, T., Asano, Y., Muto, A., Kawakami, K., Suzuki, Y., Kojima, D., Fukada, Y.
Proceedings of the National Academy of Sciences of the United States of America   116(10): 4651-4660 (Journal)
Registered Authors
Fukada, Yoshitaka, Kawakami, Koichi, Kojima, Daisuke, Muto, Akira, Ogawa, Yohey, Shiraki, Tomoya
color vision, cone opsin, photoreceptor development, transcription factor, zebrafish retina
MeSH Terms
  • Animals
  • Color
  • Color Vision
  • Gene Expression Regulation
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Rod Opsins/genetics
  • Rod Opsins/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
30765521 Full text @ Proc. Natl. Acad. Sci. USA
Color discrimination in the vertebrate retina is mediated by a combination of spectrally distinct cone photoreceptors, each expressing one of multiple cone opsins. The opsin genes diverged early in vertebrate evolution into four classes maximally sensitive to varying wavelengths of light: UV (SWS1), blue (SWS2), green (RH2), and red (LWS) opsins. Although the tetrachromatic cone system is retained in most nonmammalian vertebrate lineages, the transcriptional mechanism underlying gene expression of the cone opsins remains elusive, particularly for SWS2 and RH2 opsins, both of which have been lost in the mammalian lineage. In zebrafish, which have all four cone subtypes, rh2 opsin gene expression depends on a homeobox transcription factor, sine oculis homeobox 7 (Six7). However, the six7 gene is found only in the ray-finned fish lineage, suggesting the existence of another evolutionarily conserved transcriptional factor(s) controlling rh2 opsin expression in vertebrates. Here, we found that the reduced rh2 expression caused by six7 deficiency was rescued by forced expression of six6b, which is a six7-related transcription factor conserved widely among vertebrates. The compensatory role of six6b was reinforced by ChIP-sequencing analysis, which revealed a similar pattern of Six6b- and Six7-binding sites within and near the cone opsin genes. TAL effector nuclease-induced genetic ablation of six6b and six7 revealed that they coordinately regulate SWS2 opsin gene expression. Mutant larvae deficient for these transcription factors showed severely impaired visually driven foraging behavior. These results demonstrate that in zebrafish, six6b and six7 govern expression of the SWS2 and RH2 opsins responsible for middle-wavelength sensitivity, which would be physiologically important for daylight vision.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes