Foxq2 determines blue cone identity in zebrafish

Most vertebrate lineages retain a tetrachromatic visual system, which is supported by a functional combination of spectrally distinct multiple cone photoreceptors, ultraviolet (UV), blue, green, and red cones. The blue cone identity is ensured by selective expression of blue (sws2) opsin, and the mechanism is poorly understood because sws2 gene has been lost in mammalian species such as mouse, whose visual system has been extensively studied. Here, we pursued loss-of-function studies on transcription factors expressed predominantly in zebrafish cone photoreceptors and identified Foxq2 as a blue cone–specific factor driving sws2 gene expression. Foxq2 has dual functions acting as an activator of sws2 transcription and as a suppressor of UV (sws1) opsin transcription in blue cones. A wide range of vertebrate species retain both foxq2 and sws2 genes. We propose that Foxq2-dependent sws2 expression is a prevalent regulatory mechanism that was acquired at the early stage of vertebrate evolution.