Regulation of axon guidance and pruning of inappropriate synapses by class 3 semaphorins are key to the development of neural circuits. Collapsin response mediator protein 2 (CRMP2) has been shown to regulate axon guidance by mediating semaphorin 3A (Sema3A) signaling; however, nothing is known about its role in synapse pruning. Here, using newly generated crmp2-/- mice we demonstrate that CRMP2 has a moderate effect on Sema3A-dependent axon guidance in vivo, and its deficiency leads to a mild defect in axon guidance in peripheral nerves and the corpus callosum. Surprisingly, crmp2-/- mice display prominent defects in stereotyped axon pruning in hippocampus and visual cortex and altered dendritic spine remodeling, which is consistent with impaired Sema3F signaling and with models of autism spectrum disorder (ASD). We demonstrate that CRMP2 mediates Sema3F signaling in primary neurons and that crmp2-/- mice display ASD-related social behavior changes in the early postnatal period as well as in adults. Together, we demonstrate that CRMP2 mediates Sema3F-dependent synapse pruning and its dysfunction shares histological and behavioral features of ASD.

中文翻译：

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CRMP2 介导 Sema3F 依赖性轴突修剪和树突棘重塑。

3 类信号素调节轴突引导和修剪不适当的突触是神经回路发展的关键。Collapsin 反应介质蛋白 2 (CRMP2) 已被证明通过介导 semaphorin 3A (Sema3A) 信号传导来调节轴突引导；然而，对其在突触修剪中的作用一无所知。在这里，使用新生成的 crmp2-/- 小鼠，我们证明 CRMP2 对体内 Sema3A 依赖性轴突引导具有中等影响，其缺陷导致周围神经和胼胝体轴突引导的轻度缺陷。令人惊讶的是，crmp2-/- 小鼠在海马体和视觉皮层的定型轴突修剪和改变的树突棘重塑中表现出明显的缺陷，这与受损的 Sema3F 信号传导和自闭症谱系障碍 (ASD) 模型一致。我们证明 CRMP2 介导原代神经元中的 Sema3F 信号传导，并且 crmp2-/- 小鼠在产后早期和成人中表现出与 ASD 相关的社会行为变化。总之，我们证明 CRMP2 介导 Sema3F 依赖性突触修剪，其功能障碍具有 ASD 的组织学和行为特征。