When evolutionary paths taken by each sex within a given species diverge, the result is behavioral differences that promote specific fitness outcomes for each sex. Despite five decades of research into the link between genes, circuits, and behavior, the molecular and synaptic mechanisms that give rise to sexually dimorphic nervous systems remain poorly understood. Our proposed research plan, DimorphicCircuits, was designed to expand knowledge on neuronal circuit development, in general, and on how sexual identity is represented in neuronal circuits to control dimorphic behavioral output, in particular. We have developed a unique system that enables the study of sexual dimorphism at the synaptic, circuit, genetic, and behavioral levels across all developmental stages. Central to this proposal is the exploration of how sex-shared neurons morph into sexually dimorphic circuits that produce varied behaviors in males and hermaphrodites. Our detailed analyses at synaptic resolution reveal how variations in connectivity contribute to significant behavioral differences. Key findings include the dimorphic propagation of mechanosensory information, the dimorphic connectivity that controls sexually dimorphic nociceptive behaviors, and the discovery of sex-specific neuromodulatory mechanisms that preserve these dimorphic states, which are essential for survival and reproductive success.
As part of this project, our lab has made significant strides in molecular neurobiology, detailing how genetic sex influences neuronal circuit assembly and function. Our transcriptomic-based approaches have yielded a developmental atlas of gene expression that highlights critical periods where sex-specific genes dictate circuit differentiation. These molecular insights are crucial for understanding the developmental and the evolutionary aspects of neuronal function. Whole-animal transcriptomics throughout development and single-cell neuronal transcriptomics data sets generated during this project provide a strong framework to investigate novel molecular determinants of dimorphic properties, with a future focus on conserved genes that could contribute to the proper function of the nervous system.
