Sretavan D W
Laboratory of Neurobiology, Rockefeller University, New York, New York 10021.
J Neurosci. 1990 Jun;10(6):1995-2007. doi: 10.1523/JNEUROSCI.10-06-01995.1990.
During development of the mammalian CNS, axons encounter multiple pathway choices on their way to central target structures. A major pathway branch point in the visual system occurs at the optic chiasm, where retinal ganglion cell axons may either enter the ipsilateral or the contralateral optic tract. To investigate whether embryonic mouse retinal ganglion cell axons, upon reaching the optic chiasm, selectively grow into the correct pathway, developing retinal ganglion cells were retrogradely labeled using either 1,1'-dioctadecyl- 3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) or fluorescent microspheres placed into the optic tract on one side. The distribution of ipsilaterally and contralaterally projecting ganglion cells in the embryo was then examined and compared to that of the adult animal. Results show that axon routing at the chiasm is already extremely adult-like as early as embryonic day 15 (E15), shortly after retinal axons arrive at the chiasm. [Retinal ganglion cell neurogenesis = E11-E18 (Drager, 1985); birth = E21.] Throughout the development of this pathway, routing errors are infrequent and are on the order of only about 3-8/1000 retinal ganglion cells. Thus, embryonic retinal ganglion cell axons do not project randomly at the optic chiasm but instead appear to be highly specific in their choice of pathway. To learn how correct pathway choices are made, retinal axons were retrogradely labeled with Dil and their trajectories at the optic chiasm were reconstructed. Results show that ipsilaterally and contralaterally projecting axons are highly intermixed as they enter the chiasm region but selectively grow into the correct pathway. For example, a contralaterally projecting axon near the entrance of the ipsilateral optic tract will turn and bypass this pathway and grow towards the midline to head into the contralateral optic tract. Similarly, axons far away from the ipsilateral optic tract frequently turn abruptly at right angles to enter the ipsilateral tract, directly crossing over contralaterally projecting axons heading to the opposite side. The sorting out of intermixed ipsilaterally and contralaterally projecting retinal axons into the appropriate optic tracts strongly suggests the presence of specific guidance cues at the optic chiasm during embryonic development. Together, results from this study demonstrate that the pattern of axon projection at the adult mammalian optic chiasm is gradually built upon a highly specific pattern of axon routing laid down early during development.
在哺乳动物中枢神经系统（CNS）的发育过程中，轴突在通往中枢目标结构的途中会遇到多种路径选择。视觉系统中的一个主要路径分支点位于视交叉处，视网膜神经节细胞轴突可以进入同侧或对侧视束。为了研究胚胎期小鼠视网膜神经节细胞轴突到达视交叉时是否会选择性地生长进入正确的路径，使用1,1'-二辛基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐（Dil）或荧光微球对一侧视束中的发育中的视网膜神经节细胞进行逆行标记。然后检查胚胎中同侧和对侧投射神经节细胞的分布，并与成年动物的分布进行比较。结果表明，早在胚胎第15天（E15），即视网膜轴突到达视交叉后不久，视交叉处的轴突路径就已经与成年时极为相似。[视网膜神经节细胞神经发生 = E11 - E18（Drager，1985）；出生 = E21。]在这条路径的整个发育过程中，路径选择错误很少见，大约每1000个视网膜神经节细胞中只有3 - 8个出现错误。因此，胚胎期视网膜神经节细胞轴突在视交叉处并非随机投射，而是在路径选择上似乎具有高度特异性。为了了解如何做出正确的路径选择，用Dil对视网膜轴突进行逆行标记，并重建它们在视交叉处的轨迹。结果表明，同侧和对侧投射的轴突在进入视交叉区域时高度混合，但会选择性地生长进入正确的路径。例如，在同侧视束入口附近的对侧投射轴突会转向并绕过这条路径，朝着中线生长以进入对侧视束。同样，远离同侧视束的轴突经常会突然直角转弯进入同侧视束，直接穿过向对侧投射的轴突。同侧和对侧投射的视网膜轴突在视交叉处相互分离并进入相应的视束，这强烈表明在胚胎发育过程中视交叉处存在特定的引导线索。总之，这项研究的结果表明，成年哺乳动物视交叉处的轴突投射模式是在发育早期建立的高度特异性轴突路径模式的基础上逐渐形成的。
