The proposed study represents a continuation of our efforts to determine the molecular basis of segmentation in the Drosophila embryo. The research plan includes three areas of research: transcriptional repression, the regulation of enhancer- promoter interactions, and the localization of posterior determinants. Transcriptional repression is essential for establishing localized stripes and bands of gene expression in the early embryo. Many or most sequence-specific repressors interact with one of two maternal corepressor proteins, Groucho or dCtBP. We will continue our efforts to determine whether these proteins mediate separate pathways of transcriptional repression. Previous studies have identified two mechanisms for regulating enhances-promoter interactions within complex genetic loci: promoter competition and insulator DNAs. There is emerging evidence for a third mechanism, promoter compatibility, whereby a given enhancer can interact with only a subset of all promoter sequences. In the Antennapedia gene complex the linked Scr and ftz genes are differentially regulated by two shared enhancers, AE1 and T1. In the Bithorax complex the shared IAB5 enhancer preferentially activates AbdB but ignores the equidistant abdA gene. We will investigate the possibility that promoter-proximal sequences contain """"""""tethering elements"""""""", which help insure that the right enhancer interacts with the proper target promoter. The localization of Oskar in the posterior plasm of the egg and early embryo depends on the directed movement of microtubules in the growing oocyte. The Oskar RNA is associated with a protein complex that includes Kinesin I, the Par-I kinase, and Staufen. Mutations in these genes cause the arrest of the microtubule/oskar complex in the center of the oocyte. Genetic screens have identified a new mutant, Sinis, that causes the mislocalization of oskar in variable positions within the cortex of the egg. We will determine whether Sinis serves as a target for the directed transport of oskar to the posterior plasm.
Showing the most recent 10 out of 70 publications
