Agenesis of the corpus callosum in Nogo receptor deficient mice.
Agenesis of the corpus callosum in Nogo receptor deficient mice.
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Nogo 受体缺陷小鼠胼胝体发育不全。
DOI：
10.1002/cne.24064
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Schnaar,RonaldL
中科院分区：
文献类型：
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作者：
Yoo,Seung-Wan;Motari,MaryG;Schnaar,RonaldL
胼胝体（CC）是哺乳动物大脑中最大的纤维束，连接双侧大脑半球。 CC 的发育取决于轴突生长锥吸引和排斥线索的适当平衡，将轴突引导至中线，然后将它们引导至对侧半球。这些线索的不平衡会导致 CC 发育不全或发育不全。 Nogo 受体（NgR1、NgR2 和 NgR3）是生长锥定向分子，以抑制损伤后轴突再生而闻名。我们报告说，缺乏Nogo受体的小鼠（NgR123缺失小鼠）表现出完全的CC不发育，这是由于包括皮质普罗布斯特束在内的异位轴突所证明的轴突误导所致。由于 CC 发育需要神经胶质细胞和神经胶质细胞衍生的生长锥排斥因子（尤其是扩散因子 Slit2），因此对它们的分布进行了研究。与野生型小鼠相比，NgR123缺失小鼠的神经胶质标记物胶质原纤维酸性蛋白（GFAP）以及胶质细胞楔形物和灰膜（CC形成所需的中线结构）处的Slit2显着增加。 NgR123缺失小鼠表现出运动协调能力下降和多动症。这些数据与以下假设一致：Nogo 受体是轴突穿过 CC 中线迁移所需的膜结合生长锥排斥因子，它们的缺失直接或间接导致中线神经胶质增生、Slit2 增加和完全 CC 发育不全。 J.Comp。内罗尔。 525:291–301，2017 年。© 2016 Wiley periodicals, Inc.
The corpus callosum (CC) is the largest fiber tract in the mammalian brain, linking the bilateral cerebral hemispheres. CC development depends on the proper balance of axon growth cone attractive and repellent cues leading axons to the midline and then directing them to the contralateral hemisphere. Imbalance of these cues results in CC agenesis or dysgenesis. Nogo receptors (NgR1, NgR2, and NgR3) are growth cone directive molecules known for inhibiting axon regeneration after injury. We report that mice lacking Nogo receptors (NgR123‐null mice) display complete CC agenesis due to axon misdirection evidenced by ectopic axons including cortical Probst bundles. Because glia and glial‐derived growth cone repellent factors (especially the diffusible factor Slit2) are required for CC development, their distribution was studied. Compared with wild‐type mice, NgR123‐null mice had a sharp increase in the glial marker glial fibrillary acidic protein (GFAP) and in Slit2 at the glial wedge and indusium griseum, midline structures required for CC formation. NgR123‐null mice displayed reduced motor coordination and hyperactivity. These data are consistent with the hypotheses that Nogo receptors are membrane‐bound growth cone repellent factors required for migration of axons across the midline at the CC, and that their absence results directly or indirectly in midline gliosis, increased Slit2, and complete CC agenesis. J. Comp. Neurol. 525:291–301, 2017. © 2016 Wiley Periodicals, Inc.