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Identification of hox-regulated targets at different time points of a developmental process

Final Activity Report Summary - HOX NETWORK (Identification of Hox-regulated targets at different time points of a developmental process)

This project aimed to study how the developmental control genes known as Hox genes control the development of different organs at different positions within the body, using as a model system the wings of the fruit fly Drosophila. In flies, only the forewing develops as a wing, while the hindwing tissue develops as a highly modified balancing organ known as a haltere. This difference depends only on the expression of the Hox gene Ultrabithorax (Ubx), which modifies both the initial patterning of the wing tissue, and the final differentiation of wing and haltere cells, which differ dramatically in size and shape.

Using the sophisticated genetics of Drosophila, we have developed a system that allows us to activate the Ubx gene specifically in the wing primordia at different times during development, without affecting its expression in the remainder of the fly. Using wing tissues isolated from flies treated in this way, we have analysed how all genes in the genome respond to the expression of Ubx protein before, during and after the dramatic developmental changes associated with metamorphosis. We find that Ubx activates or represses hundreds of target genes in the wing alone, with a time course which suggests that most of these changes are direct rather than indirect responses. The targets include other developmental control genes, as we would have expected from previous studies, but also many genes involved in the final development of adult structures - such as, for example, the genes encoding components of the insect external skeleton. These results confirm the hypothesis that the Hox genes regulate targets at many different levels in the hierarchy of genetic control.

Perhaps the most interesting and novel aspect of our results is that in this one tissue, Ubx regulates a largely different set of targets at each of the three stages that we have examined. This aspect of Hox gene function, which has not previously been explored, must reflect the integration of Hox control, which defines aspects of spatial pattern, with the hormonal control pathways that control the onset of metamorphosis and the temporal sequence of development. Our results therefore provide the basis for future studies, which will analyse how these two critical aspects of developmental control interact to orchestrate the correct sequence of gene activity during development.