Ten-m3 is required for the development of topography in the ipsilateral retinocollicular pathway.
Ten-m3 is required for the development of topography in the ipsilateral retinocollicular pathway.
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DOI：
10.1371/journal.pone.0043083
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Leamey CA
中科院分区：
文献类型：
--
作者：
Dharmaratne N;Glendining KA;Young TR;Tran H;Sawatari A;Leamey CA
查看视觉空间同一部分的同侧和对侧突出的视网膜轴突的对齐是双眼视觉的基础。虽然在调节对侧地形的机制方面已经取得了很大进展，但对于调节同侧轴突的映射以使它们与对侧轴突对齐的机制知之甚少。利用小鼠视网膜丘通路提供的有利模型，我们进行了顺行追踪实验，证明同侧视网膜轴突在出生后的最初几天内开始在上丘（SC）中形成终末区（TZ）。这些在出生后第 11 天就显得成熟。重要的是，由同侧突出的视网膜轴突形成的 TZ 从一开始就与来自相同视网膜位置的对侧突出的轴突形成的 TZ 存在空间偏移。这种模式与成人视觉矫正所需的模式一致。我们进一步证明，同亲性跨膜糖蛋白 Ten-m/Odz/Teneurin 家族的成员 Ten-m3 是同侧视网膜丘陵地形的重要调节因子。 Ten-m3 mRNA 在发育中的 SC 中以高内侧到低外侧梯度表达。这在地形上与其高腹侧到低背侧视网膜梯度相对应。在 Ten-m3 基因敲除小鼠中，对侧腹颞轴突适当地靶向喙内侧 SC，而同侧轴突沿 SC 的内侧轴和喙尾轴表现出显着的靶向错误，导致初级 TZ 尾部移位，以及形成次级尾外侧移位 TZ。除了这些显着的同侧特异性标测误差之外，对侧和同侧视网膜丘 TZ 都表现出更微妙的形态变化。我们的结论是，成人视位的重要方面是通过同侧和对侧轴突对内在引导线索的不同敏感性来建立的。此外，我们表明 Ten-m3 在此过程中发挥着关键作用，对于同侧视网膜丘脑通路的绘制尤其重要。
The alignment of ipsilaterally and contralaterally projecting retinal axons that view the same part of visual space is fundamental to binocular vision. While much progress has been made regarding the mechanisms which regulate contralateral topography, very little is known of the mechanisms which regulate the mapping of ipsilateral axons such that they align with their contralateral counterparts. Using the advantageous model provided by the mouse retinocollicular pathway, we have performed anterograde tracing experiments which demonstrate that ipsilateral retinal axons begin to form terminal zones (TZs) in the superior colliculus (SC), within the first few postnatal days. These appear mature by postnatal day 11. Importantly, TZs formed by ipsilaterally-projecting retinal axons are spatially offset from those of contralaterally-projecting axons arising from the same retinotopic location from the outset. This pattern is consistent with that required for adult visuotopy. We further demonstrate that a member of the Ten-m/Odz/Teneurin family of homophilic transmembrane glycoproteins, Ten-m3, is an essential regulator of ipsilateral retinocollicular topography. Ten-m3 mRNA is expressed in a high-medial to low-lateral gradient in the developing SC. This corresponds topographically with its high-ventral to low-dorsal retinal gradient. In Ten-m3 knockout mice, contralateral ventrotemporal axons appropriately target rostromedial SC, whereas ipsilateral axons exhibit dramatic targeting errors along both the mediolateral and rostrocaudal axes of the SC, with a caudal shift of the primary TZ, as well as the formation of secondary, caudolaterally displaced TZs. In addition to these dramatic ipsilateral-specific mapping errors, both contralateral and ipsilateral retinocollicular TZs exhibit more subtle changes in morphology. We conclude that important aspects of adult visuotopy are established via the differential sensitivity of ipsilateral and contralateral axons to intrinsic guidance cues. Further, we show that Ten-m3 plays a critical role in this process and is particularly important for the mapping of the ipsilateral retinocollicular pathway.
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