The development of multicellular animals from a single-celled fertilized egg is a complex process that requires extensive communication between enormous numbers of cells. It is the long-term goal of this research to better understand how cellular signaling is used to direct activities that sculpt a multicellular organism. The approach taken in this project is to study the mechanisms by which one evolutionarily conserved signal cascade, the Janus kinase (JAK) signaling pathway, regulates development in the fruit fly, Drosophila melanogaster, as a model for developmental cell signaling in other animals, including humans. Study of JAK signaling in fruit flies is particularly attractive because it is amenable to genetic and developmental manipulation and because only the three Unpaired (Upd) family proteins are believed to act as signals for the JAK pathway. Previous studies have examined the developmental functions of Upd and Upd2. The current project will use genetic, developmental, and biochemical methods to determine the functions of Upd3 in development and JAK signaling, as well as to determine the mechanisms by which the Unpaired family proteins act together to regulate JAK signaling during development. It is expected that mechanisms uncovered in this system will be applicable to multi-gene families of cell signaling proteins found in other animals. This project will provide opportunities for the education and training of young biologists and will be the primary training activity of graduate students in the laboratory, with additional roles played by undergraduates seeking to learn about biology through conducting independent research projects.