Grant: Discovery Grants Program - Individual

Nearly all animals exhibit some form of segmentation along the anterior-posterior (head to tail) axis. An example of segmentation of the human body plan is the vertebrae of the backbone; each vertebra represents an individual segment and each vertebra has a unique shape or morphology. I am interested in two general questions: first how the correct number of segments is established; and second how segments are assigned a unique morphology. The insect body plan is divided into 14 segmental units along the anterior-posterior axis. The fruitfly fushi tarazu gene encodes the FTZ protein required for determining the correct number of segments that form during development, and the proboscipedia (pb) and Sex combs reduced (Scr) genes encode proteins PB and SCR required for assigning unique identities to 3 segments. FTZ, SCR and PB share a DNA-binding protein domain called the homeodomain (HD). HD-containing proteins are transcription factors that regulate transcription, which is the process that converts information stored in DNA to RNA that is then read by the protein synthesis machinery. Though many of the genes regulated by FTZ, PB and SCR are extensively characterized, there is a lack of knowledge about how these transcription factors work to bring about changes in the pattern of gene transcription. HD-transcription factors have been analyzed for over twenty years, but one key element missing to understand how they work is a complete description of their functional domains. Mapping the functional domains has proven difficult. This difficulty is due to HD-containing proteins being composed of small peptide motifs that make only small contributions to overall activity. We are now identifying these small motifs and describing their requirements. This knowledge will greatly enhance our understanding of the mechanistic logic behind the segmentation of the insect body plan, and as HD-containing proteins are also required during the segmentation of the vertebrate body plan, the work in flies is of general biological significance and application.