Drosophila melanogaster has been the preeminent experimental system for studies of the genetic control of developmental fate. Studies of this organism have shown the importance of two gene clusters, the bithorax complex (BX-C) and the Antennapedia complex (ANT-C), in controlling determinative decisions. However, flies are evolutionarily very advanced insects, and at present we have little basis to evaluate which features of Drosophila development represent fundamental mechanisms and which are specialized adaptations of this taxon. An integrated developmental genetic and molecular analysis of the control of developmental fate in a more primitive insect, the red flour beetle Tribolium casteaneum is proposed. Preliminary studies have already identified a homeotic complex (HOM-C) which appears to represent the juxtaposed equivalent of the ANT-C and BX-C, and have generated more than 25 new mutations affecting this complex. Future studies will use an available balancer chromosome and HOM-C deficiencies to saturate the complex with lethal and visible mutations; such a high resolution genetic analysis heretofore has been inconceivable outside of Drosophila. The phenotypes of these mutations at all stages of the life cycle will be described, with special emphasis on variants associated with lethality. Further, molecular studies to determine the organization of the HOM-C and its constituent genes, and to describe the temporal and spatial specificities of their expression will be done. The sequences in the complex will be cloned by homology to Drosphila sequences. Drosophila melanogaster is the most sophisticated experimental system available for the study of genetic control of development. But until an equally powerful but different eukaryotic organism can also be studied, it is difficult to know whether the developmental mechanisms uncovered in Drosophila can be generalized to all eukaryotic systems. Dr. Denell and his associates will develop such a system in Tribolium castaneum, the red flour beetle.
