IBN-9630161 PI: Yedvobnik A fundamental question in developmental biology is how cells choose to develop into specific types. For example, the earliest stages of neural development involve a decision-making process. Groups of uncommitted cells must decide whether to enter a neural pathway of development, or choose an alternate pathway that ends with epidermal (skin) development. Such processes are essential and are shared by a wide range of organisms. In Drosophila this decision is regulated by a group of genes called the neurogenic loci, that apparently mediate intercellular communication. Molecular studies of these loci have demonstrated that they encode membrane, cytoplasmic and nuclear proteins, consistent with their role in cell communication.The mastermind (mam) gene is a member of the neurogenic loci and codes for a protein with a novel structure. Interestingly, it is the only member of the neurogenic loci where sequence information has not provided a clear model for function. Consequently, additional functional studies of mam are necessary. It is expected that a complete characterization of the mam protein will provide new insights into neural development in Drosophila and probably other organisms. Although a large body of information is available on most of these genes, the role of the neurogenic locus mastermind (mam), has remained enigmatic. mam shows genetic interactions with a number of other neurogenic loci, suggesting that it plays an integral role in the pathway. mam codes for a nuclear protein which has been demonstrated to bind multiple chromosome sites. These data suggest a role in gene regulation. Using genetic and molecular approaches the site of mam action within the pathway will be defined, and also t several hypotheses of mam function will be tested. Genetic studies will be used to position mam function relative to the linear sequence of action of other neurogenic proteins. Analysis of physical associations between mam and other neurogenic proteins will be used to test hypotheses of mam function. In combination with other work in progress these studies will provide significant insight into the mode of action of this unusual protein.
