Haque Rizwanul, Setty Hagar, Lorenzo Ramiro, Stelzer Gil, Rotkopf Ron, Salzberg Yehuda, Goldman Gal, Kumar Sandeep, Halber Shiraz Nir, Leifer Andrew M, Schneidman Elad, Laurent Patrick, Oren-Suissa Meital
Department of Brain Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.
Sci Adv. 2025 Jul 11;11(28):eadv9106. doi: 10.1126/sciadv.adv9106.
Sex-specific behaviors are often attributed to differences in neuronal wiring and molecular composition, yet how genetic sex shapes the molecular architecture of the nervous system at the individual neuron level remains unclear. Here, we use single-cell RNA sequencing to profile the transcriptome of sex-shared neurons in adult males and hermaphrodites. We uncover widespread molecular dimorphism across the nervous system, including in previously unrecognized neuron-types such as the touch receptors. Neuropeptides and signaling-related genes exhibit strong sex-biased expression, particularly in males, reinforcing the notion that neuropeptides are crucial for diversifying connectome outputs. Despite these differences, neurotransmitter identities remain largely conserved, indicating that functional dimorphism arises through modulatory, not identity-defining, changes. We show that sex-biased expression of neurotransmitter-related genes correlates with bias in outgoing synaptic connectivity and identify regulatory candidates for synaptic wiring, including both shared and sex-specific genes. This dataset provides a molecular framework for understanding how subtle regulatory differences tune conserved circuits to drive sex-specific behaviors.
性别特异性行为通常归因于神经元连接和分子组成的差异，但基因性别如何在单个神经元水平塑造神经系统的分子结构仍不清楚。在这里，我们使用单细胞RNA测序来分析成年雄性和雌雄同体中性别共享神经元的转录组。我们发现整个神经系统中存在广泛的分子二态性，包括在以前未被识别的神经元类型，如触觉感受器。神经肽和信号相关基因表现出强烈的性别偏向性表达，尤其是在雄性中，强化了神经肽对于多样化连接组输出至关重要的观点。尽管存在这些差异，神经递质的种类在很大程度上保持保守，这表明功能二态性是通过调节性变化而非身份定义性变化产生的。我们表明，神经递质相关基因的性别偏向性表达与传出突触连接的偏向性相关，并确定了突触连接的调控候选基因，包括共享基因和性别特异性基因。该数据集为理解细微的调控差异如何调整保守回路以驱动性别特异性行为提供了一个分子框架。
