LAY ABSTRACT Principal Investigator: Cahill, Gregory Proposal Number: IBN 9728697 In all organisms, internal biological clocks drive daily (or circadian) rhythms in physiological states, resulting in sleep-wake cycles and other behavioral rhythms. Genetic studies of insects and non-animal organisms have identified genes that code for many of these molecular gears, but very few clock genes have been identified in vertebrate animals. The goal of this project is to understand how the components of the circadian system interact to produce daily rhythms, and to determine how the clock is assembled during embryonic development. Recent work in this laboratory has demonstrated that clock cells are located in the pineal gland and retina, and that these cells release a hormone, melatonin, in a circadian rhythm. Behavioral activity levels are also controlled by a biological clock. The first major objective of this project is to determine the causal relationships among these phenomena. Is behavioral rhythmicity driven by melatonin rhythms, and is behavior regulated by clocks in the pineal gland, the retinas or some other clock7 The second objective is to determine when and how rhythms of melatonin and behavior are initiated during development from a single cell embryo to a fully formed vertebrate animal. Fish embryos are fertilized and develop external to the mother. This allows manipulation of physiological and environmental conditions to test hypotheses about how the biological clocks that control melatonin and behavior are initiated and set. This initial characterization of the zebrafish circadian system will provide the baseline information necessary to fully exploit emerging zebrafish genetic information and technology in future studies of vertebrate circadian clock mechanisms.
