The long-term objective of this project is to understand how genes specify the functioning of a behavioral system. The anatomically simple neuromuscular system of the nematode Caenorhabditis elegans consists of diverse types of neurons and muscles while being sufficiently small and simple to allow a complete description of its cells, cell lineage, and neural connectivity, facilitating the identification and analysis of anatomical, developmental, and functional abnormalities caused by mutations. Studies of the C. elegans egg-laying system and of the neuromuscular systems that control behaviors often coordinately regulated with egg laying, such as locomotion and feeding, offer opportunities for the analysis of a broad variety of fundamental biological problems of relevance to many human disorders. The major issue that this project will address is the mechanisms used by animals to respond to environmental cues and stresses. More specifically, this project will determine how low oxygen levels and multichromatic light (color) affect C. elegans egg-laying behavior and locomotion, respectively, and will use these C. elegans behaviors as readouts to analyze important evolutionarily conserved pathways that respond to such cues and stresses. The genetic, molecular, cellular, and neural-circuit bases of these responses will be defined. The major focus will be on mechanisms that mediate behavioral responses to oxygen deprivation, which profoundly affects cellular and organismic physiology in humans and is responsible for the cardiac damage in heart attacks as well as for ischemic damage to the kidneys, nervous system and other organs. The evolutionarily conserved EGLN/HIF pathway mediates responses to oxygen deprivation, has been implicated in many human disorders, and has defined major therapeutic targets for cancer. This aim will identify new components of this important pathway and reveal how this pathway acts both broadly and with cell-type specificity to control animal physiology and behavior. The second and more exploratory aim will determine how, despite lacking eyes and opsins (the class of photoreceptor proteins thought to be essential for color discrimination), C. elegans can distinguish different colors. Color detection is used by animals of diverse phyla to sense and respond to colorful natural environments. The proposed studies of the responses of C. elegans to multichromatic light will address a fundamental and intriguing biological question: what mechanisms allow cells that lack opsins to respond to multichromatic light? More specifically, this aim will determine how the evolutionarily conserved Epithelial Sodium Channel (ENaC), which in mammals is crucial for fluid and ion homeostasis, functions in C. elegans to mediate responses to colored light. These studies should both reveal novel aspects of ENaC channel regulation and function and provide novel insights into opsin-independent photobiological responses, which are displayed by a variety o...