Transcriptional control of brain sex differentiation in Diptera

Across diverse animals, sex differentiation generates distinct patterns of innate social behaviors. The neural circuits underlying these behaviors are 'hard-wired', with neuronal development programs ensuring the same circuit wiring across individuals. Aspects of their development are modified by effectors of sex determination. These factors, including Fruitless in Drosophila melanogaster and Estrogen Receptor α in mammals, shape sex-specific behaviors by altering neuron numbers, axon and dendrite anatomy, synaptic connectivity, and neuronal physiology to allow for distinct neural connections and behavioral repertoires. While the sex-sensitive transcription factors were identified long ago, the transcriptional mechanisms through which they affect brain development are only recently coming into focus. Defining the molecular mechanisms by which sex-sensitive transcription factors act to alter the brain and behavior has profound implications for 1) how genomic regulatory elements pattern complex behavior, 2) the critical developmental windows in which neurons and brain regions can be altered in pleiotropic ways, and 3) the discrete developmental events underlying circuit assembly and how those events are susceptible to disruption. Here, we review how the Fruitless transcription factor acts in context-specific ways to induce sex differences in circuit organization in Diptera.