Molecular Genetics of Segment Determination in Drosophila

9506206 Mann The development of a multicellular animal requires that all cells have two types of information: where they are relative to their neighbors (positional information) and what structure they should generate (identity information). In Drosophila melanogaster, the homeotic selector genes link these two pieces of information: their large cis regulatory regions interpret positional information and their protein products control cellular identities by regulating the transcription of downstream target genes. These target genes are important to characterize to understand how homeotic genes determine identities. Therefore, homeotic target genes were isolated using a molecular screen. Among these targets is a putative transcription factor that is predicted to control neuroblast identities in the central nervous system and a potential component of the cytoskeleton. Interestingly, the human homologs of both genes are implicated in oncogenesis, suggesting that, in some contexts, they can control cellular differentiation and/or proliferation. To investigate their wild type functions during Drosophila development, loss- and gain-of-function mutations of these genes will be generated. The consequences these mutations have on both embryonic morphology and gene expression will be analyzed. Using in vivo misexpression assays, the functions of the wild type and oncogenic forms will be compared. In addition, the homeotic-responsive cis regulatory sequences that control the expression of these genes will be studied using in vivo reporter gene constructs and in vitro DNA-binding assays. Together, these experiments will provide an understanding of how positional information is translated into identity information by the homeotic genes. ***