近日，美国斯坦福大学骆利群及其小组的最新研究揭示了排斥作用指导嗅觉回路中的突触配对。2025年11月19日出版的《自然》杂志发表了这项成果。

通过单细胞转录组的基因筛选，课题组人员发现了3对CSP，分别是Toll2-Ptp10D、Fili–Kek1和Hbs/Sns–Kirre，它们在发育中的果蝇嗅觉回路中介导非伴侣嗅觉受体神经元（ORN）轴突和投射神经元（PN）树突之间的排斥相互作用。每个CSP对在选择的ORN-PN伙伴中表现出相反的表达模式。在ORN中，每一个CSP的缺失都会导致与PN中同伴CSP的缺失相似的突触伴侣匹配缺陷，并且由一个CSP过表达引起的错误靶向表型可能会被其同伴CSP的缺失所抑制。所有CSP对在其他脑区也有差异表达。总之，他们的数据表明，在发育过程中，多个排斥CSP对通过阻止神经元与非同源伙伴形成连接来确保精确的突触伙伴匹配。

据介绍，神经元在选择突触伙伴方面表现出非凡的精确性。虽然细胞表面蛋白（CSPs）介导发育中的轴突和树突之间的吸引性相互作用已被证明指导突触伴侣匹配，但排斥相互作用的作用程度尚不清楚。

附：英文原文

Title: Repulsions instruct synaptic partner matching in an olfactory circuit

Author: Li, Zhuoran, Lyu, Cheng, Xu, Chuanyun, Hu, Ying, Luginbuhl, David J., Caspi-Lebovic, Asaf B., Priest, Jessica M., zkan, Engin, Luo, Liqun

Issue&Volume: 2025-11-19

Abstract: Neurons exhibit extraordinary precision in selecting synaptic partners. Although cell-surface proteins (CSPs) that mediate attractive interactions between developing axons and dendrites have been shown to instruct synaptic partner matching1,2, the degree to which repulsive interactions have a role is less clear. Here, using a genetic screen guided by single-cell transcriptomes3,4, we identified three CSP pairs, Toll2–Ptp10D, Fili–Kek1 and Hbs/Sns–Kirre, that mediate repulsive interactions between non-partner olfactory receptor neuron (ORN) axons and projection neuron (PN) dendrites in the developing Drosophila olfactory circuit. Each CSP pair exhibits inverse expression patterns in the select ORN–PN partners. Loss of each CSP in ORNs led to similar synaptic partner matching deficits as the loss of its partner CSP in PNs, and mistargeting phenotypes caused by overexpressing one CSP could be suppressed by loss of its partner CSP. All CSP pairs are also differentially expressed in other brain regions. Together, our data reveal that multiple repulsive CSP pairs work together to ensure precise synaptic partner matching during development by preventing neurons from forming connections with non-cognate partners.

DOI: 10.1038/s41586-025-09768-4

Source: https://www.nature.com/articles/s41586-025-09768-4