Genetic dissection of sexual behaviour. (360G-Wellcome-106189_Z_14_Z)

1. What are your research questions? We use Drosophila courtship behaviour to study how sex-specific neural circuitry and behaviours are established during development by the action of complex networks of genes. Our studies focus on two pivotal transcription factors of the sex-determination hierarchy, fruitless (fru) and doublesex (dsx) that act together to specify and configureboth the anatomy and physiology of sex-specific neural circuitry. We employ cutting edge genetic, molecular and behavioural approaches to understand how fru and dsx direct the genetic programs responsible for the assembly of the underlying dimorphic circuitry that governs sex-specific circuit function. Ultimately we aim to understand how activity in functioning dimorphic neural circuits gives rise to a different sex-specific behavioural repertoire in the male and female fly.We will address the following specific questions: What are the regulatory principles governing the assembly of sex-specific circuits? Biological differences between males and females result from two processes: sex determination and differentiation. Sex determination controls whether the male or female sexual differentiation pathway will be followed. Sex differentiation involves many genetically regulated, hierarchical developmental steps. The sex of an animal determines its sexual behaviour and orientation. In the fruit fly, sexual differentiation of the neural circuits underlying sexualbehaviors is dependent on the action of the Dsx and Fru transcription factors. Selective expression of Dsx and Fru define cell-type-specific developmental programs that govern connectivity and lay the foundations through which innate sexual behaviors are genetically predetermined. We are investigating the fundamental question of how the Fru and Dsx transcription factors achieve this by regulating the expression of target genes. Since dsx is both structurally and functionally conserved throughout the animal kingdom, similarities in the molecular mechanisms that control sexual differentiation are likely to be identified. What are the neural circuits that encode sex-specific behaviours? Sexually dimorphic behaviours arise from anatomical and functional differencesin neural circuits. In some cases, the sex differences are qualitative such that particular neurons are unique to one sex, in others a quantitative sex difference may represent a dimorphism in the same cell or the molecular characteristics of shared neurons. In the fly, manyof these dimorphisms reside in central brain neurons. This suggests that males and females detect many of the same external signals but process them differently to produce distinct behavioural responses. We are interested in how these sex differences relate to sexually dimorphic behavioural outputs. Addressing these questions in the fly is now a realistic goal. By identifying the neural and molecular components of sex-specific neural circuits, and mapping functional connectivity, we can define causal relationships between circuit activity and sexual behaviour.