Segregation of Ipsilateral Retinal Ganglion Cell Axons at the Optic Chiasm Requires the Shh Receptor Boc
Segregation of Ipsilateral Retinal Ganglion Cell Axons at the Optic Chiasm Requires the Shh Receptor Boc
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DOI：
10.1523/jneurosci.3778-09.2010
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发表时间：
2010-01-06
影响因子：
5.3
通讯作者：
Charron, Frederic
中科院分区：
文献类型：
--
作者：
Fabre, Pierre J.;Shimogori, Tomomi;Charron, Frederic
视交叉处向对侧和同侧投射的视网膜神经节细胞（RGC）轴突的模式对于建立双眼视觉至关重要。对侧轴突从视神经行进至视束时穿过视交叉中线。相反，同侧轴突偏离视交叉并在同侧视束中继续延伸，避开视交叉中线。这种现象背后的分子机制尚不完全清楚。在这里，我们发现 Sonic Hedgehog (Shh) 受体 Boc 在发育中视网膜的同侧 RGC 中富集。加上中线存在 Shh，这种互补的表达模式使我们推测 Shh 可能会排斥交叉处的同侧 RGC 轴突。与这一假设一致，我们发现只有Boc阳性的RGC轴突在体外响应Shh而收缩，并且这种反应在Boc突变的RGC中消失。在体内，我们发现 Boc 是视交叉处同侧轴突正常分离所必需的，相反，对侧 RGC 中的 Boc 表达会阻止其轴突穿过视交叉。总之，这些结果表明 Shh 通过其受体 Boc 排斥视交叉处的同侧 RGC 轴突。这项工作确定了视交叉处轴突分离所需的新分子途径。
The pattern of contralaterally and ipsilaterally projecting retinal ganglion cell (RGC) axons at the optic chiasm is essential for the establishment of binocular vision. Contralateral axons cross the chiasm midline as they progress from the optic nerve to the optic tract. In contrast, ipsilateral axons deviate from the chiasm and continue in the ipsilateral optic tract, avoiding the chiasm midline. The molecular mechanism underlying this phenomenon is not completely understood. Here we show that the Sonic Hedgehog (Shh) receptor Boc is enriched in ipsilateral RGCs of the developing retina. Together with the presence of Shh at the midline, this complementary expression pattern led us to hypothesize that Shh might repel ipsilateral RGC axons at the chiasm. Consistent with this hypothesis, we found that only Boc-positive RGC axons retract in vitro in response to Shh and that this response is lost in Boc mutant RGCs. In vivo, we show that Boc is required for the normal segregation of ipsilateral axons at the optic chiasm and, conversely, that Boc expression in contralateral RGCs prevents their axons from crossing the optic chiasm. Together, these results suggest that Shh repels ipsilateral RGC axons at the optic chiasm via its receptor Boc. This work identifies a novel molecular pathway required for the segregation of axons at the optic chiasm.