Insulin and epidermal signals independently shape sexually dimorphic neurite branching in C. elegans

Sexual dimorphism in neural wiring and behavior arises from both intrinsic genetic programs and environmental cues, yet how these factors interact to shape neuronal morphogenesis remains unclear. Here, we investigate sexually dimorphic collateral branching in PVP cholinergic interneurons of Caenorhabditis elegans. In hermaphrodites, PVP branches form near the vulva and exhibit dynamic morphologies enriched with synaptic proteins for dense core vesicles but not synaptic vesicles, suggesting a role in selective neuropeptide transmission. We find that sex identity is necessary but not sufficient for PVP branching. Sex identity engages autonomous insulin signaling via the FOXO transcription factor DAF-16 to promote branch formation and modulate dynamic branch morphologies according to nutritional status. However, external epithelial cues from primary vulval cells are both necessary and sufficient to induce branching independent of sex identity. Despite acting through distinct pathways, insulin signaling and vulval cues converge on F-actin cytoskeletal remodeling. These sexually dimorphic PVP branches modulate egg-laying behavior in hermaphrodites. Our study uncovers a multilayered regulatory framework integrating intrinsic sex-specific programs and extrinsic signaling to shape sexually dimorphic neural circuits.