The patterning of binocular vision requires distinct molecular pathways for inputs arising from each side of the nervous system. Recent studies have demonstrated important roles for members of the Ten-m/Odz/teneurin family in the development of ipsilateral retinal projections. Here, we further highlight the significance of this gene family in visual development by identifying a role for Ten-m4 during the formation of the ipsilateral projection in the mouse. Ten-m4 was found to be expressed in the retina, dorsal lateral geniculate nucleus (dLGN), superior colliculus (SC), and primary visual cortex (V1) during development. Anterograde and retrograde tracing experiments in Ten-m4 knockout (KO) mice revealed a specific increase in ipsilateral retinal ganglion cells projecting to dLGN and SC. This increase was most prominent in regions corresponding to temporal retina. Consistent with this, EphB1 expression in the retina around the time of decussation was enhanced in this temporal region for KO mice, suggesting that the increased size of the ipsilateral population arises due to an increased number of retinal ganglion cells remaining ipsilaterally at the optic chiasm due to EphB1-mediated repulsion. The ectopic ipsilaterally targeted retinal ganglion cell projection observed in Ten-m4 KOs was associated with changes in response to ethologically relevant visual stimuli. Together, these data demonstrate a requirement for Ten-m4 in the establishment of ipsilateral projections from the retina, which likely acts in combination with other Ten-m members (Ten-m2 and Ten-m3) to promote the formation of functional binocular circuits.

中文翻译：

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十米四在双眼视觉回路的建立中发挥着独特的作用

双眼视觉的模式化需要不同的分子通路来接收来自神经系统每一侧的输入。最近的研究证明了 Ten-m/Odz/teneurin 家族成员在同侧视网膜投射发育中的重要作用。在这里，我们通过确定 Ten-m4 在小鼠同侧投影形成过程中的作用，进一步强调了该基因家族在视觉发育中的重要性。在发育过程中，10-m4 被发现在视网膜、背侧膝状体核 (dLGN)、上丘 (SC) 和初级视觉皮层 (V1) 中表达。在 Ten-m4 基因敲除 (KO) 小鼠中进行的顺行和逆行追踪实验显示投射到 dLGN 和 SC 的同侧视网膜神经节细胞有特定的增加。这种增加在对应于颞叶视网膜的区域最为突出。与此相一致的是，在 KO 小鼠的这个颞区，交叉交叉时视网膜中的 EphB1 表达增强，这表明同侧细胞群数量的增加是由于视交叉处同侧视网膜神经节细胞数量增加所致对 EphB1 介导的排斥。在 Ten-m4 KO 中观察到的异位同侧靶向视网膜神经节细胞投射与对行为学相关视觉刺激的反应变化有关。总之，这些数据表明在建立同侧视网膜投射时需要 Ten-m4，这可能与其他 Ten-m 成员（Ten-m2 和 Ten-m3）共同作用以促进功能性双眼回路的形成。