Netrin-1 is crucial for the establishment of the dorsal column-medial lemniscal system
Netrin-1 is crucial for the establishment of the dorsal column-medial lemniscal system
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DOI：
10.1111/j.1471-4159.2004.02460.x
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发表时间：
2004-06-01
影响因子：
4.7
通讯作者：
Sato, M
中科院分区：
文献类型：
--
作者：
Kubota, C;Nagano, T;Sato, M
背柱-内侧丘系系统是介导触觉和肢体位置觉的重要感觉通路。在这个系统中，来自背柱核中的二级神经元的轴突形成内部弓状纤维，穿过延髓内的腹侧中线（底板），然后投射到丘脑作为内侧丘系。在这里，我们表明，Netrin-1，这是从地板在延髓分泌，是必不可少的背柱内侧丘系系统的形成。在小鼠胚胎第11天左右，来自背柱核的轴突穿过中线。同时，Netrin-1 mRNA及其受体DCC（在结直肠癌中缺失）分别在底板和连合轴突中表达。在我们的外植体培养实验中，胚胎11天龄的突变Netrin-1纯合小鼠的底板不吸引来自ICR小鼠背柱核的轴突，而来自野生型同窝小鼠的轴突吸引。此外，我们观察到，尽管背柱核在突变小鼠中原位发育，但它们的轴突不被吸引向底板：它们不穿过中线，并在胚胎17天龄的突变Netrin-1纯合小鼠中保持同侧，不形成内部弓状纤维。
The dorsal column-medial lemniscal system is a significant sensory pathway that mediates touch and limb position sense. In this system, axons from the second-order neurons in the dorsal column nuclei form the internal arcuate fibers, cross the ventral midline (floor plate) within the medulla oblongata, and then project to the thalamus as the medial lemniscus. Here we demonstrate that Netrin-1, which is secreted from the floor plate in the medulla oblongata, is indispensable to the formation of the dorsal column-medial lemniscal system. Axons from the dorsal column nuclei cross the midline at around embryonic day 11 in mice. Concurrently, Netrin-1 mRNA and its receptor DCC (deleted in colorectal cancer) were expressed in the floor plate and commissural axons there, respectively. In our explant culture experiments, the floor plates of the embryonic 11-day-old mutant Netrin-1 homozygous mice did not attract axons from the dorsal column nuclei of ICR mice, while those from the wild type littermates did. Moreover, we observed that although the dorsal column nuclei developed in situ in mutant mice, their axons were not attracted toward the floor plate: they did not cross midline and remained ipsilaterally, without forming the internal arcuate fibers, in embryonic 17-day-old mutant Netrin-1 homozygous mice.