Another major attraction of the zebrafish relates to its pineal gland. In mammals, light input to the clock is perceived uniquely by a subset of intrinsically photosensitive retinal ganglion cells in
Another major attraction of the zebrafish relates to its pineal gland. In mammals, light input to the clock is perceived uniquely by a subset of intrinsically photosensitive retinal ganglion cells in the eye. This photic information reaches the central oscillator in the suprachiasmatic nucleus (SCN) via the retinohypothalamic tract, induces transcriptional changes in clock genes (e.g., period1 and period2), and so synchronizes rhythmic neuronal activity [13,14]. Signals from the SCN then regulate the activity of many other targets, including melatonin synthesis in the pineal gland [15]. In non-mammalian vertebrates, including zebrafish, the pineal gland contains all elements required for photic entrain-ment and circadian rhythm generation: it is photoreceptive and contains an intrinsic circadian oscillator [16,17]. Fish pineal cells are classical photoreceptor cells with structural and functional similarities to retinal photoreceptors. Pineal and retinal photore-ceptor cells share a similar set of genes, or, in certain cases, par-alogs [18]. The fish pineal contains an intrinsic circadian clock that drives rhythmic synthesis of the hormone melatonin. Mela-tonin levels are high at night and low during the day as a result of regulated transcription and stability of serotonin-N-acetyl-transferase (AANAT), the key enzyme for melatonin synthesis. Zebrafish, like other teleosts have two aanat genes: aanat1 that is expressed predominantly in the retina and aanat2 that is ex-pressed in the pineal gland and to a limited extent in the retina [18,19]. Activity of this enzyme is dictated by the circadian clock and also shows a rapid suppression in response to illumination during the night [20,21]. Thus the pineal gland is considered to serve as central pacemaker: transducing environmental light information into a neural and a neuroendocrine signal. Many studies now focus on identifying the control mechanisms direct-ing the first appearance of rhythmic melatonin synthesis during development, its regulation by the clock and light as well as pineal-specific patterns of gene expression.