**10. Role of redox signaling in cellular-clock regulation by light in zebrafish**

It has been proposed that the light-dependent transcription of *zCry1a* and *zPer2* is controlled through the production and removal of cellular reactive oxygen species (ROS) [16]. ROS were originally thought to act solely as toxic metabolites, because they react with components of DNA, proteins, and lipids and exert oxidative stress [64]. However, ROS are also ideally suited to be signaling molecules because they are small and can easily diffuse over short distances within a cell. In addition, mechanisms for ROS production and their rapid removal (for example, via catalase) are present in almost all cell types [64, 65]. In various organisms, light induces ROS production, which leads to an altered redox status in cells [28]. In zebrafish cells, this light-induced redox change transduces photic signals and leads to the transactivation of *zCry1a* and *zPer2* [16, 62, 66]. Importantly, light increases intracellular catalase activity by increasing the expression of *catalase*, an event that occurs after the maximum expression of the *zCry1a* and *zPer2* genes has been reached [16]. This increased catalase activity diminishes light-induced cellular ROS levels, resulting in decreased expression of the *zCry1a* and *zPer2* genes.

The toxic effects of oxidative stress have been linked to cellular ROS production induced by light-activated flavin-containing oxidases [67]. The absorbance of light in the near violet-blue region by these enzymes activates them and induces photoreduction of the flavin adenine dinucleotide (FAD) moiety, leading to ROS production. Accordingly, signaling by flavoproteins frequently induces a change in

**Figure 3.** *Light signaling pathway regulating clock gene induction in zebrafish.*

the redox state of cells [67]. Recent studies have provided evidence that flavincontaining oxidases are responsible for the light-dependent production of ROS that are second messengers coupling photoreception to photoreactivation and the circadian clock in zebrafish [62, 66] (**Figure 3**).
