**9. Light signaling pathway regulating cellular clocks in zebrafish cells**

Studies using cultured zebrafish cells have identified cellular signaling cascades involved in the light-dependent regulation of cellular clocks. In several organisms, external stimuli are connected to a cell's nucleus via MAPK signaling pathways [61]. There are three major MAPKs: c-JUN N-terminal kinase (JNK), p38, and ERK. Light has been reported to activate these signaling cascades in zebrafish cells. Using a pharmacological approach, it was established that light-induced *zPer2* transactivation requires the ERK signaling pathway [15]. It has also been proposed that light-induced ERK activation triggers *zCry1a* transcription, whereas light-induced p38 activation suppresses it, highlighting a MAPK-mediated cross-regulatory mechanism for the expression of circadian-clock genes [21]. As mentioned above, evidence strongly suggests the involvement of the ERK pathway in the light-input system of the mammalian circadian clock. Thus, these findings are consistent with the idea that several aspects of the complex mammalian photo-signal transduction pathway involved in the regulation of circadian clocks are more easily investigated, both pharmacologically and molecularly, using cultured zebrafish cells. In addition, it was reported that the light-activated JNK signaling pathway induces expression of *zCry1a* and *zPer2* [62]. Notably, in contrast to these studies, it has recently been reported that the light-activated p38 pathway facilitates the expression of *zCry1a* and *zPer2* and that the ERK/MAPK signaling pathway is not involved in the lightinduced expression of *zCry1a* and *zPer2* [62, 63]. The reason for these contradictory results is unknown.
