0212373<br/>Moss<br/><br/>Developmental timing is fundamental to all multicellular organisms. For tissues and organs to form properly, developmental events must occur in the proper succession with the appropriate synchrony. The mechanisms that explicitly govern the timing of these events are not well understood in any organism. Valuable insights, however, have come from the investigation of heterochronic genes of the nematode Caenorhabditis elegans. Dr. Moss will investigate an new and important heterochronic gene, lin-46, which helps specify the stage-appropriate fates of cells during the animal's larval development. The LIN-46 protein acts early in the developmental timing pathway, downstream of the key regulators LIN-14 and LIN-28. Proteins related to LIN-46 in plants and animals are known to mediate protein-protein interactions. Therefore, to control developmental timing LIN-46 is likely to interact with proteins that coordinate the behaviors of cells and may be regulated by LIN-14 and LIN-28.<br/><br/>The work outlined in this proposal will address how LIN-46 governs developmental timing from two aspects. First, Dr. Moss will elucidate the molecular relationship between the lin-46 and other heterochronic genes by determining whether lin-46 expression is regulated by lin-28 and lin-14, whether they act in the same cells, and whether they are in a linear genetic pathway. Second he will characterize the interaction of LIN-46 with other proteins. He predicts that at least one other protein encoded in the C. elegans genome interacts physically with LIN-46 and is necessary for its function. He will search for other proteins that interact with LIN-46 using molecular and genetic approaches.<br/><br/>The long-range impact of this work will be an understanding of the molecular basis of developmental timing regulation by LIN-46 and how it has evolved. What is learned about developmental timing in C. elegans may be widely applicable to other animals. The process of developmental timing is of broad biological interest because its importance in the evolution of animal form.