Reciprocal repulsions instruct the precise assembly of parallel hippocampal networks.

Reciprocal repulsions instruct the precise assembly of parallel hippocampal networks.
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DOI:
10.1126/science.abg1774
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发表时间:
2021-06-04
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Luo L
Luo L
中科院分区:
其他
文献类型:
--
作者:
Pederick DT;Lui JH;Gingrich EC;Xu C;Wagner MJ;Liu Y;He Z;Quake SR;Luo L

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哺乳动物的内侧和外侧海马网分别优先处理与空间和物体相关的信息。然而,在发展过程中组装这种平行网络的基础机制在很大程度上仍然不清楚。在这里,我们证明,在小鼠中,细胞表面分子Teneurin-3(Ten3)和LatroPhilin-2(Lphn2)分别在内侧和外侧海马网络中的互补表达,指导了CA1到下丘脑的连接在这两个网络中的精确组装。在内侧网络中,Ten3+轴突被靶来源的Lphn2排斥,揭示了Lphn2/Ten3介导的排斥和Ten3/Ten3介导的吸引共同控制CA1轴突的精确靶向选择。在外侧网络中,Lphn2+CA1轴突通过Ten3+靶的排斥作用被限制在Lphn2+靶上。我们的发现表明,平行海马网的组装遵循由相互排斥指导的“Ten3→Ten3,Lphn2→Lphn2”规则。随着小鼠海马区网络的发展,多功能细胞表面蛋白的互补表达和相互排斥指示轴突寻找靶标。
Mammalian medial and lateral hippocampal networks preferentially process spatial- and object-related information, respectively. However, the mechanisms underlying the assembly of such parallel networks during development remain largely unknown. Here, we show that, in mice, complementary expression of cell-surface molecules Teneurin-3 (Ten3) and Latrophilin-2 (Lphn2) in the medial and lateral hippocampal networks, respectively, guides the precise assembly of CA1-to-subiculum connections in both networks. In the medial network, Ten3+ axons are repelled by target-derived Lphn2, revealing that Lphn2/Ten3-mediated repulsion and Ten3/Ten3-mediated attraction cooperate to control precise target selection of CA1 axons. In the lateral network, Lphn2+ CA1 axons are confined to Lphn2+ targets via repulsion from Ten3+ targets. Our findings demonstrate that assembly of parallel hippocampal networks follows a ‘Ten3→Ten3, Lphn2→Lphn2’ rule instructed by reciprocal repulsions. Complementary expression and reciprocal repulsion of multifunctional cell-surface proteins instruct axons in search of targets as the mouse hippocampal networks develop.
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