Genetic, Temporal and Developmental Differences Between Melatonin Rhythm Generating Systems in the Teleost Fish Pineal Organ and Retina J. Falco ´ n,  Y. Gothilf,y S. L. Coon,z G. Boeuf  and D. C. Kleinz  Laboratoire Arago, UMR 7628, CNRS and University Pierre and Marie Curie, Banyuls sur Mer, France. yDepartment of Zoology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel. zNIH, Laboratory of Developmental Neurobiology, Bethesda, MD, USA. Key words: fish, retina, pineal organ, melatonin, arylalkylamine N-acetyltransferase. Abstract Complete melatonin rhythm generating systems, including photodetector, circadian clock and melatonin synthesis machinery, are located within individual photoreceptor cells in two sites in Teleost fish: the pineal organ and retina. In both, light regulates daily variations in melatonin secretion by controlling the activity of arylalkylamine N-acetyltransferase (AANAT). However, in each species examined to date, marked differences exist between the two organs which may involve the genes encoding the photopigments, genes encoding AANAT, the times of day at which AANAT activity and melatonin production peak and the developmental schedule. We review the fish pineal and retinal melatonin rhythm generating systems and consider the evolutional pressures and other factors which led to these differences. Melatonin is an important component of the vertebrate circadian system; it is made in two sites involved in phototransduction, the pineal gland and retina. Pineal-derived melatonin controls the daily rhythm in circulating melatonin and provides a hormonal signal of night time to the organism. This signal plays a role in the timing and control of a number of biological rhythms (1, 2). Retinal melatonin is thought to have a local paracrine function related to photic adaptation (3). In all vertebrates, melatonin production follows a circadian pattern controlled by a complex rhythm generating system. Such a system is typically composed of three basic elements, a photodetector, an endogenous clock and melatonin synthesizing machinery. In Teleost fish, complete melatonin rhythm generating systems are located within individual photoreceptor cells in the pineal gland and retina (4). In most species, such as pike and zebrafish, this includes the three elements discussed above: a photodetector, circadian clock and melatonin synthesis machinery. As a result, when pineal glands from these species are placed in organ culture, melatonin production follows a circadian pattern (4, 5), which is a reflection of the clock. Light can modulate the circadian pattern of melatonin synthesis in two ways: (i) by resetting the clock and (ii) by blocking clock-stimulation of melatonin synthesis. By contrast to Teleost fish with ‘clock-containing’ melatonin rhythm gener- ating systems, the clock is absent in trout and other salmonids. As a result, light is the only element controlling melatonin synthesis (4, 5). This species-dependent difference is one reason why investi- gators are interested in how melatonin is regulated in fish. How- ever, this is not the only reason. Differences also exist in the genes expressed in each tissue, which encode proteins with similar functions. However, the most puzzling differences between the Teleost fish pineal organ and retina are in the timing of the melatonin rhythm and responses to light. The Teleost fish pineal gland offers no surprises: it follows the same pattern seen in all vertebrates in that melatonin synthesis generally parallels the nocturnal increase in activity of the penultimate enzyme in melatonin synthesis, arylalkylamine N-acetyltransferase (AANAT; EC 2.3.1.87). AANAT controls the rate at which serotonin is converted to N-acetylserotonin (5), which earned this enzyme the title of ‘the melatonin rhythm enzyme’. However, the retina is full of surprises. In trout, for example, retinal AANAT is elevated by lighting, not depressed, as is the case with pineal AANAT. In addition, in pike, the peak in retinal AANAT mRNA occurs in the light during late afternoon, in light, 6h before pineal AANAT mRNA peaks in the middle of the night. These and other differences will be reviewed here; in addition, some of the selective pressures and other factors responsible for Journal of Neuroendocrinology, 2003, Vol. 15, 378–382 # 2003 Blackwell Publishing Ltd Correspondence to: Dr J. Falco ´n, Laboratoire Arago, UMR 7628, CNRS and University Pierre and Marie Curie, BP 44, F-66651 Banyuls sur Mer, France (e-mail: falcon@obs-banyuls.fr).