<p>While sexual dimorphisms in brain structure and function are well-documented across species, the specific features and mechanisms underlying sex differences in individual neurons and how these differences drive behavior remain largely unknown. Most research has focused on sex-specific neurons, limiting insight into how shared neural circuits diverge between sexes. Using C. elegans, we investigated sex differences in shared neuronal modules through two approaches: 1. To explore circuit-level sex differences we dissected the neuronal properties of a sexually dimorphic circuit shared by both sexes, focusing on the circuit responsible for mechanosensation (the detection of mechanical stimulation), specifically touch sensation, in both sexes of C. elegans. We discovered that touch is detected through a distinctly different set of neurons in each sex, and this process involves unique molecules and receptors that operate in a sex-specific manner. One of these key molecules is the ion channel TMC-1, critical for hearing in humans. This study identified for the first time that touch can be sensed differently by the two sexes of an organism. 2. To investigate genetic sex differences at the level of individual sex-shared neurons, we mapped the nervous system of C. elegans in both sexes using single-cell RNA sequencing. By analyzing gene expression patterns in the nervous system of both sexes derived from the transcriptomic profiles, we discovered novel sexually dimorphic neurons and their relevance to behavior and neuronal function. We further conducted computational analysis on our single-cell data set to predict synaptic connectivity regulators based on gene expression, leading to the identification of several candidate genes now under investigation. Taken together, our work revealed multiple cellular and molecular pathways that operate differently between the sexes, shedding light on how an organism's sexual identity shapes the organization of its nervous system.</p>
