9418793 Siegfried The goal of this proposal is to understand the mechanism of cell- cell communication that regulates the development of the fruit fly Drosophila melanogaster embryo. Wingless is a protein that is expressed in a subset of cells in the embryo that can signal to neighboring cells that don't express the Wingless protein and regulate their fate. The mechanism of this cell signalling is unknown but we have identified a number of other molecules that are involved in the signalling pathway. Zeste white 3 kinase, which has the ability to modify other proteins by adding phosphate to them, and potentially alter their activity, is one component of this pathway. We propose to identify the proteins which Zeste white 3 kinase does modify and to determine how Zeste white 3 kinase activity is itself modulated. The investigation of Zeste white 3 will lead to a greater understanding of the Wingless signalling. This is relevant to the understanding of vertebrate growth and development since Wingless is similar to proteins found in mice that are required for normal development. In addition, the Wingless signalling pathway is likely to be conserved in vertebrates since components such as Zeste white 3 also have vertebrate counterparts. ***