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Decoding sexual dimorphism of the sex-shared nervous system at single-neuron resolution
Rizwanul Haque1,2, Hagar Setty1,2, Ramiro Lorenzo3
1Department of Brain Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
Science Advances
|July 11, 2025
Summary
Genetic sex shapes the molecular landscape of individual neurons in C. elegans. This study reveals widespread molecular differences, particularly in signaling genes, influencing neuronal connectivity and sex-specific behaviors.
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 poorly understood.
- Understanding how genetic sex influences neural molecular architecture is crucial for deciphering behavioral dimorphism.
Purpose of the Study:
- To investigate the molecular differences between neurons in adult male and hermaphrodite C. elegans.
- To identify genes and regulatory mechanisms contributing to sex-specific neuronal wiring and behavior.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was employed to profile the transcriptomes of sex-shared neurons.
- Comparative analysis of gene expression patterns between male and hermaphrodite C. elegans nervous systems.
Main Results:
- Widespread molecular dimorphism was observed across neuron types, including touch receptors.
- Neuropeptide and signaling genes showed significant sex-biased expression, especially in males.
- Neurotransmitter identities were largely conserved, suggesting modulatory roles in functional dimorphism.
Conclusions:
- Genetic sex profoundly impacts neuronal molecular composition, driving functional diversification of conserved circuits.
- Sex-biased gene expression correlates with synaptic connectivity biases, highlighting regulatory candidates for wiring.
- This molecular framework aids in understanding the neural basis of sex-specific behaviors.

