Many regulatory genes of flies, mice, humans, and other metazoan organisms share a specific sequence motif known as the homeobox. A group of these genes share other characteristics as well, including their ordered arrangement in large gene complexes. The significance of these highly conserved patterns of organization is unknown, but suggests that mechanisms for the genetic control of development may be highly conserved, even while may involve processes not yet encountered in simple regulatory systems. An example of such a highly ordered gene complex is the bithorax complex, which plays a key role in the determination of segmental identity during development of fruit fly Drosophila melanogaster. The work described in this proposal contributes to the genetic and molecular analysis of the bithorax complex, concentrating upon one regulatory region: the infra-abdominal-5,7 (iab-5,7) region of the Abdominal-B domain. This region, which is 60kb in size and located 3' of the gene it controls, is required for the proper development of three specific segments of the fly. Three major projects are proposed: (1) Recovery of new mutations within the iab-5,7 region using mutagenic agents which cause small deletions. (2) Comparison of the iab-5,7 region in D. melanogaster and a distant Drosophila species, D. virilis, by sequence analysis and cross-species transformation experiments. (3) Functional analysis of cis- regulatory elements within iab-5,7 using P-factor-mediated transformation. How regulatory genes such as the bithorax region of Drosophila control the genetic determinants leading to body morphology is a fundamental mystery and the results from this project should give us a little more insight into the process.***//
