Foxq2 determines blue cone identity in zebrafish.

In vertebrates, daylight vision is mediated by a combination of spectrally distinct cone photoreceptor cells. Most vertebrate lineages retain a tetrachromatic cone system in which each cone photoreceptor subtype expresses one of four cone opsins: UV- (SWS1), blue- (SWS2), green- (RH2), and red-sensitive (LWS) opsins. Each cone subtype identity is established by a transcriptional network directing selective opsin gene expression in single photoreceptors. Our knowledge is limited regarding gene expression mechanisms for the middle wavelength-sensitive opsin genes, sws2 and rh2, because they are absent in mammalian species such as mouse, whose visual system has been extensively studied. Our previous studies identified homeobox transcription factors, Six6 and Six7, as crucial regulators of both sws2 and rh2 gene expression in zebrafish. Yet it remains unclear how these two opsin genes are selectively expressed in a cone subtype-specific manner. Here we pursued loss-of-function studies on transcription factors expressed predominantly in zebrafish cone photoreceptors and found that sws2 expression requires a forkhead box transcription factor, Foxq2, which is retained in many vertebrates having sws2 gene. A quantitative gene expression analysis using purified pools of the four cone subtypes revealed that foxq2 was expressed only in SWS2 cone subtype. foxq2 expression was abrogated in six6a/six6b/six7 knock-out zebrafish, which is deficient in SWS2 cone subtype. Forced expression of foxq2 fully restored sws2 expression in six7 knock-out fish without affecting rh2 expression. We propose a core transcriptional network that determines SWS2 cone subtype identity in the tetrachromatic vertebrate.