Netrin-1 and DCC mediate axon guidance locally at the optic disc: Loss of function leads to optic nerve hypoplasia
Netrin-1 and DCC mediate axon guidance locally at the optic disc: Loss of function leads to optic nerve hypoplasia
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DOI：
10.1016/s0896-6273(00)80373-6
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发表时间：
1997-09-01
期刊：
影响因子：
16.2
通讯作者：
Sretavan, DW
中科院分区：
文献类型：
--
作者：
Deiner, MS;Kennedy, TE;Sretavan, DW
胚胎视网膜神经节细胞(RGC)轴突必须向视盘延伸并通过视盘生长，才能离开眼睛进入视神经。在胚胎小鼠眼内，我们发现轴突引导分子Netrin-1的免疫反应特异性地位于RGC轴突周围盘中的神经上皮细胞上，RGC轴突表达Netrin受体DCC(在结直肠癌中缺失)。在体外，抗DCC抗体减少了对netrin-1的RGC轴突生长反应。在netrin-1和DCC缺失的胚胎中，RGC轴突到达视盘的路径没有受到影响，但轴突未能进入视神经，导致视神经发育不良。因此，Netrin-1通过DCC似乎在视盘局部引导RGC轴突，而不是在远距离，显然反映了Netrin-1蛋白在视盘产生netrin-1的细胞附近的定位。
Embryonic retinal ganglion cell (RGC) axons must extend toward and grow through the optic disc to exit the eye into the optic nerve. in the embryonic mouse eye, we found that immunoreactivity for the axon guidance molecule netrin-1 was specifically on neuroepithelial cells at the disk surrounding exiting RGC axons, and RGC axons express the netrin receptor, DCC (deleted in colorectal cancer). In vitro, anti-DCC antibodies reduced RGC neurite outgrowth responses to netrin-1. In netrin-1- and DCC-deficient embryos, RGC axon pathfinding to the disc was unaffected; however, axons failed to exit into the optic nerve, resulting in optic nerve hypoplasia. Thus, netrin-1 through DCC appears to guide RGC axons locally at the optic disc rather than at long range, apparently reflecting the localization of netrin-1 protein to the vicinity of netrin-1-producing cells at the optic disc.