Elucidating the molecular mechanisms of behavioral sexual dimorphism

Sexual dimorphism in various species does not only contribute to physical differences, but is also a major cause of the differences in behavior. At the molecular level, recent studies reveal extensive sex-biased gene expression changes in the nervous system. However, the mechanisms that regulate these differences are poorly understood. I propose to identify the underlying mechanism using C. elegans as an in vivo model. The recently reconstructed posterior nervous system of the male shows that many of the shared neurons between the male and the hermaphrodite are strongly sexually dimorphic in their wiring, but the mechanisms leading to these changes haven't been studied yet. First, I will define the sexual differences for patterned locomotory behavior. Although there are clear motility differences between C. elegans sexes, quantitative data have not been obtained yet. I will use automated tracking methods to determine the kinematic features that define male motility. By analyzing the locomotive features of laser-ablated candidate neurons and mutants, the circuits and neurons involved in generating dimorphic behaviors will be identified. Second, I will masculinize specific portions of the hermaphrodite nervous system using genetic manipulations and cell-specific promoters. Third, to identify transcripts that are selectively expressed in neurons from masculinized animals versus hermaphrodites I will combine genomic approaches. Whole-genome and cell-specific sequencing will be used for genome-wide and single-neuron gene expression profiling. Using these approaches, I will identify the molecular changes in the core nervous system responsible for sex-biased behaviors.