Specification of Morphogenetic Pathways Through Differential Regulation of Deformed Target Genes

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*** 9514246 Mahaffey, James The long term goal of this project is to understand how certain genes specify regional development in the fruit fly, Drosophila. In particular the specification of anterior-posterior body pattern will be studied. The families of genes to be studies are the homeotic and related hox complex, which specify segment identity in the fly. Though the genetics of this process has been studied extensively, there is very little known about how a specific homeobox gene product (protein) directs the development of a particular segmental morphology. The studies described here will address how differential gene expression and segment identity are specified by the product of the Deformed homeotic gene during maxillary segment development. The studies are designed to elucidate how the Deformed homeoprotein can, in different maxillary cells, specify different genetic pathways determining distinct cell fates. These experiments 1) examine the role of the Deformed homeoprotein and other factors in activating expression of Deformed specific target genes by comparing the regulation of maxillary enhancers from two known target genes and 2) characterize a newly identified gene whose product is necessary, along with Deformed, to activate certain target genes and thereby influence the morphogenetic pathway maxillary cells follow. To examine target gene activation, the role of various factors including the Deformed homeoprotein will be examined by altering the structure of the enhancer region of specific target genes and by analyzing the activity of chimeric enhancers. Further, it is known that two maxillary gene enhancers have differing requirements for a newly identified factor. Genetic analysis indicates that this factor behaves as a cofactor with one gene allowing selective activation of certain target genes thereby influencing which developmental pathway certain cells will follow. A genetic and molecular study of the gene encoding the new factor will be undertaken to determine it s structure and its influence on target homeobox genes required for formation of maxillary appendages. ***