Harrison 9723944 The coordinated proliferation and differentiation of distinct cell types is critical to the proper development and maintenance of any multicellular organism. For this coordination to occur, cells must have a means to communicate with one another. The broad long-term objectives of this research are to elucidate mechanisms of cell-cell signaling and to understand how different signals are interpreted to regulate developmental events. Toward these goals, the Janus kinase (JAK) signaling pathway will be studied in Drosophila melanogaster. This system will be used because it is developmentally important, relatively simple, and is conserved between flies and mammals. In mammals, the pathway is know to be comprised of the non-receptor tyrosine kinases (JAKs) and the signal transducers and activators of transcription (STATs). In flies, one JAK (hopscotch) and one STAT (marelle) gene have been recently identified. The genetic and developmental manipulations available in Drosophila make it an ideal model system to further study JAK/STAT signaling. These approaches will complement and extend the biochemical analyses of the pathway conducted in mammalian cells. Mutational analysis has already uncovered a new component of JAK/STAT signaling in Drosophila, unpaired (upd). An understanding of the involvement of upd in JAK signaling is central to the research proposed here. Other molecules integral to the JAK pathway, or that strongly interact with components of the pathway, will be identified and characterized using the genetic tools available in Drosophila. The specific goals of this research are to: 1) Characterize the unpaired locus at the molecular level 2) Determine the functions of the Upd product in JAK signaling 3) Characterize the roles of Upd function in Drosophila development 4) Identify other components of and factors interacting with the JAK pathway
