Decoding sexual dimorphism of the sex-shared nervous system at single-neuron resolution

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Sex-specific behaviors are linked to neuronal differences, but the molecular basis at the single-neuron level is not well understood.
• Understanding how genetic sex influences neuronal molecular composition is crucial for deciphering behavioral dimorphism.

Purpose of the Study:

• To investigate the molecular differences between neurons in male and hermaphrodite C. elegans at the single-cell level.
• To identify genes and regulatory mechanisms responsible for sex-specific neuronal wiring and behavior.

Main Methods:

• Single-cell RNA sequencing was employed to profile the transcriptomes of sex-shared neurons in adult C. elegans males and hermaphrodites.
• Analysis focused on identifying sex-biased gene expression patterns and their correlation with synaptic connectivity.

Main Results:

• Widespread molecular dimorphism was observed across the C. elegans nervous system, including in touch receptor neurons.
• Neuropeptide and signaling genes showed strong sex-biased expression, especially in males, suggesting a role in diversifying neural circuit outputs.
• Neurotransmitter identities were largely conserved, indicating that functional sex differences arise from modulatory changes rather than identity alterations.
• Sex-biased gene expression correlated with biased synaptic connectivity, and potential regulatory genes for synaptic wiring were identified.

Conclusions:

• Genetic sex profoundly influences the molecular identity of individual neurons, leading to functional dimorphism in conserved circuits.
• Neuropeptides and signaling pathways are key mediators of sex-specific neuronal function and behavior.
• This research provides a molecular framework for understanding how subtle genetic sex-driven regulatory differences tune neural circuits to produce distinct behaviors.