| During the process of animal development, initially uniform fields of cells acquire distinct identities. One manifestation of this process is the generation of unique morphology within a metameric series, such as the segments of the Drosophila larva or the vertebrae of the mammalian skeleton. The Drosophila homeotic genes, and the homologous murine Hox genes, control morphologic diversification of the segmental pattern. These genes encode transcription factors that direct groups of cells down specific developmental pathways, by controlling the expression of so-called 'downstream' genes. To understand homeotic/Hox gene function, we must therefore identify these downstream genes and analyze their roles in mediating homeotic control of development. Unfortunately, few targets of the Drosophila homeotic genes, and even fewer of the murine Hox genes, have been identified.; The work described here begins with a screen for novel targets of homeotic gene regulation. As a result of this screen, the Drosophila segmentation gene odd-paired was cloned and identified as a target of homeotic gene regulation. Genetic analysis demonstrates that odd-paired, like the homeotic genes that regulate its expression, is required for morphogenesis of specific constrictions in the embryonic midgut late in development. Temporal analysis of odd-paired function supports the hypothesis that odd-paired functions downstream of homeotic genes in the genetic hierarchy controlling midgut constriction formation.; Phenotypic analysis also demonstrates that odd-paired is required in the early embryo, prior to homeotic gene expression, for segmental subdivision of the ectoderm and for formation of the mesodermal component of the midgut. Thus, odd-paired functions upstream of the homeotics to control ectodermal and mesodermal development, in addition to its proposed function downstream of the homeotics in controlling midgut constriction formation. Spatial analysis of odd-paired function in the early embryo suggests that inductive interactions between the ectoderm and mesoderm play a role in mesodermal development. |
