Ten-m2 Is Required for the Generation of Binocular Visual Circuits
Ten-m2 Is Required for the Generation of Binocular Visual Circuits
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DOI：
10.1523/jneurosci.4708-12.2013
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发表时间：
2013-07-24
影响因子：
5.3
通讯作者：
Leamey, Catherine A.
中科院分区：
文献类型：
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作者：
Young, Timothy R.;Bourke, Michael;Leamey, Catherine A.
功能性双眼视觉要求来自两个视网膜的输入在中央视觉区域内被整合和精确地组织。先前的研究已经证明了Ten-m/Odz/teneurin家族的一个成员Ten-m3在同侧视网膜投射的映射中的重要作用。在这里，我们已经确定了一个独特的作用，另一个密切相关的家庭成员，Ten-m2，在小鼠视觉系统的同侧投影的形成。Ten-m2在发育小鼠的视网膜、背外侧膝状体核（dLGN）、上级丘（SC）和初级视皮层（V1）中观察到表达。在Ten-m2基因敲除（KO）小鼠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的特异性减少。这种减少在与腹侧视网膜对应的区域中最为突出。未观察到同侧或对侧投射的地形变化。虽然关键的同侧命运决定因子Zic 2的表达似乎没有改变，但在腹侧视网膜中观察到其下游靶点之一EphB 1的显著减少，表明Ten-m2可能与该分子途径相互作用。免疫组化c-fos，神经活动标记物，揭示了该地区的V1驱动的同侧输入减少科斯，而同侧到对侧的反应，有助于双眼激活视觉诱发电位记录的比例也减少。最后，一个新的两个选择游泳任务揭示了特定的赤字与背侧视野。这些数据表明，在建立同侧的预测，从而产生的双眼电路，哺乳动物的视觉功能的关键十平方米的要求。
Functional binocular vision requires that inputs arising from the two retinae are integrated and precisely organized within central visual areas. Previous studies have demonstrated an important role for one member of the Ten-m/Odz/teneurin family, Ten-m3, in the mapping of ipsilateral retinal projections. Here, we have identified a distinct role for another closely related family member, Ten-m2, in the formation of the ipsilateral projection in the mouse visual system. Ten-m2 expression was observed in the retina, dorsal lateral geniculate nucleus (dLGN), superior colliculus (SC), and primary visual cortex (V1) of the developing mouse. Anterograde and retrograde tracing experiments in Ten-m2 knock-out (KO) mice revealed a specific decrease in ipsilateral retinal ganglion cells projecting to dLGN and SC. This reduction was most prominent in regions corresponding to ventral retina. No change in the topography of ipsilateral or contralateral projections was observed. While expression of a critical ipsilateral fate determinant, Zic2, appeared unaltered, a notable reduction in one of its downstream targets, EphB1, was observed in ventral retina, suggesting that Ten-m2 may interact with this molecular pathway. Immunohistochemistry for c-fos, a neural activity marker, revealed that the area of V1 driven by ipsilateral inputs was reduced in KOs, while the ratio of ipsilateral-to-contralateral responses contributing to binocular activation during visually evoked potential recordings was also diminished. Finally, a novel two-alternative swim task revealed specific deficits associated with dorsal visual field. These data demonstrate a requirement for Ten-m2 in the establishment of ipsilateral projections, and thus the generation of binocular circuits, critical for mammalian visual function.