Molecular Biology of Neural Development, Institut de Recherches Cliniques de Montréal, Montreal, Quebec, Canada.
J Neurosci. 2010 Jan 6;30(1):266-75. doi: 10.1523/JNEUROSCI.3778-09.2010.
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.
视交叉处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。对侧轴突在从视神经向视束行进过程中穿过视交叉中线。相比之下，同侧轴突偏离视交叉并继续在同侧视束中，避开视交叉中线。这一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 在发育中的视网膜同侧 RGC 中富集。与中线存在 Shh 一起，这种互补的表达模式使我们假设 Shh 可能在视交叉处排斥同侧 RGC 轴突。与这一假设一致，我们发现只有 Boc 阳性 RGC 轴突在体外对 Shh 有反应而回缩，而 Boc 突变的 RGC 中则没有这种反应。在体内，我们表明 Boc 对于视交叉处同侧轴突的正常分离是必需的，反之亦然，即 Boc 在对侧 RGC 中的表达可防止它们的轴突穿过视交叉。总之，这些结果表明 Shh 通过其受体 Boc 在视交叉处排斥同侧 RGC 轴突。这项工作确定了在视交叉处分离轴突所必需的新的分子途径。
