Pheromone regulation of gene expression in the brain

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DESCRIPTION (provided by applicant): We will couple a novel model (honey bee) with powerful new genomic resources (cDNA microarray and a soon-to-be-completed complete genome sequence) to study how pheromones regulate gene expression in the brain. Endocrine-mediated behavioral development in the bee is regulated in a manner strikingly similar to the regulation of mammalian reproductive development, by primer pheromones, and honeybee queen mandibular pheromone (QMP) is one of the few chemically characterized primer pheromones known to affect endocrine-mediated physiological and behavioral development. We will: 1) Determine how Kr-hl expression is related to pheromone regulation of behavior, Kr-ht, the first pheromone regulated gene identified in a higher brain center, is a transcription factor and is regulated in two socially relevant ways. We will test the hypothesis that QMP repression of Kr-hl expression is related to this pheromone's inhibitory effects on endocrine-mediated behavioral maturation with a set of social, behavioral, and pharmacological manipulations. 2) Determine the effect of Kr-hl expression on brain cell neuroanatomy and synaptic structure using immunocytochemistry and the powerful MARCM technique in Drosophila and complementary approaches in bee (with Tzumin Lee). 3) Identify downstream targets of Kr-ht transcriptional regulation. As a transcription factor, Kr-hl presumably functions by controlling expression of other genes that would play more direct functional roles in neuronal remodeling or regulating foraging behavior. We will use a multi-pronged approach to identify these genes involving, identification the consensus binding sequence of the bee and Drosophila Kr-hl proteins; bioinformatics (with Hugh Robertson); characterization of proteins associated with Kr-hl by peptide sequencing and chromatin remodeling assays; microarray experiments in both bees and flies; and chromatin immunoprecipitation (with Craig Mizzen) The principal significance of this research is that it will improve our molecular understanding of how chemical communication influences neural and behavioral plasticity.