Netrin signaling shapes sexually dimorphic neurite branching of a sex-shared interneuron in C. elegans
Year: 2026
Type: preprint
Abstract: Sexually dimorphic behaviors arise from underlying differences in neural circuit architecture between the sexes, yet the molecular mechanisms that establish these structural differences remain poorly understood. In Caenorhabditis elegans , the sex-shared interneuron AVG exhibits sexually dimorphic synaptic connectivity, offering a model for investigating the development of sexually dimorphic neuronal morphology. Here, we identified that AVG displays male-specific neurite branching and demonstrated that the conserved axon guidance cue UNC-6/Netrin and its receptor UNC-40/DCC are essential for this structural remodeling. Cell-specific manipulation of sexual identity revealed that male identity confers branching competence to AVG. Loss of UNC-6 or UNC-40 abolished branch formation, whereas loss of the alternate Netrin receptor UNC-5/Unc5 had no detectable effect. Cell-specific rescue experiments showed that UNC-40 functions in AVG through its UNC-6 binding domains. Furthermore, genetic ablation of the male-specific presynaptic neuron PCA, which expresses unc-6 , diminished AVG branch length, establishing PCA as a candidate local source of UNC-6. Together, our findings support a model in which presynaptic UNC-6/Netrin cues from male-specific neurons promote dimorphic neurite branching in sex-shared neurons, illustrating how evolutionarily conserved signaling molecules are redeployed during sexual maturation to sculpt sex-specific neural circuits.
Institution: Dongguk University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7220724376