Abstract
In the fruit fly Drosophila melanogaster, male-specific splicing and translation of the Fruitless transcription factor (FruM) alters the presence, anatomy, and/or connectivity of >60 types of central brain neurons that interconnect to generate male-typical behaviors. While the indispensable function of FruM in sex-specific behavior has been understood for decades, the molecular mechanisms underlying its activity remain unknown. Here, we take a genome-wide, brain-wide approach to identifying regulatory elements whose activity depends on the presence of FruM. We identify 436 high-confidence genomic regions differentially accessible in male fruitless neurons, validate candidate regions as bona fide, differentially regulated enhancers, and describe the particular cell types in which these enhancers are active. We find that individual enhancers are not activated universally but are dedicated to specific fru+ cell types. Aside from fru itself, genes are not dedicated to or common across the fru circuit; rather, FruM appears to masculinize each cell type differently, by tweaking expression of the same effector genes used in other circuits. Finally, we find FruM motifs enriched among regulatory elements that are open in the female but closed in the male. Together, these results suggest that FruM acts cell-type-specifically to decommission regulatory elements in male fruitless neurons.
Highlights
In many species, male and female brains generate distinct behavioral repertoires
Courtship behavior in male Drosophila melanogaster is controlled by a well-defined neural circuit that is labeled by the male-specific transcription factor Fruitless (FruM)
By examining the activity of these regulatory elements in vivo, we found that their activity was 1) sexually dimorphic and 2) specific to a single class of FruM neurons, suggesting that FruM acts on different chromatin targets in different neuron classes comprising the courtship circuit
Summary
The ability to compare behavior, brains, neurons, and gene expression across the sexes makes sexually dimorphic behaviors premier models for understanding structure-function relationships in neural circuits In both vertebrates and invertebrates, master regulators of neuronal sex are induced downstream of the sex determination hierarchy and alter the composition of specific neurons and brain areas [1,2,3,4]. Circuit changes produced by these transcription factors are complex and heterogeneous, including differences in the numbers of specific types of neurons, their anatomy and connectivity, and their mature physiology [2,3,4,5,6,7] These sex-specific alterations to circuits cause males and females to perform sex-specific innate behaviors. While the causal role of these master regulators in shaping behavior is clear, the transcriptional events through which they do so are opaque
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