Remarkable complexity and variability of corticospinal tract defects in adult Semaphorin 6A knockout mice.
Remarkable complexity and variability of corticospinal tract defects in adult Semaphorin 6A knockout mice.
复制标题
成年 Semaphorin 6A 敲除小鼠皮质脊髓束缺陷的显着复杂性和变异性。
DOI：
10.1016/j.brainres.2018.12.041
复制
发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Okada;T.;Keino-Masu;K.;Suto;F.;Mitchell;K.J.;Masu;M.
皮质脊髓束（CST）具有复杂而长的轨迹，其起源于大脑皮质并终止于脊髓。脑信号蛋白6A（Semaphorin 6A，Sema 6A）是脑信号蛋白家族的一员，是CST轴突导向的重要调节因子。先前的研究表明，出生后Sema 6A突变小鼠在中脑-后脑边界和髓质存在CST缺陷。然而，异常纤维在Sema 6A突变体大脑中的路径仍然未知。在这项研究中，我们进行了免疫染色的CST纤维的三维重建，重新评估的细节异常CST轨迹在成年Sema 6A突变小鼠的大脑。我们的研究结果表明，轴突导向缺陷报告在出生后早期的突变体一致观察到成年。然而，大脑切片的3D分析揭示的这些异常轨迹比之前想象的更加复杂和多变。此外，3D分析使我们能够识别一些新的异常投影模式。首先，一个子集的纤维，分离和下降平行于主束投影横向在脑桥尾侧，随后改变方向转向尾侧，并延伸到延髓。第二，一些异常纤维在基本上偏离原始束后返回到正确的轨迹。第三，一些纤维正常到达锥体交叉，但没有进入背索。切片免疫染色结合3D重建是追踪长投射纤维和检查正常和异常动物的整个神经束的有力方法。
The corticospinal tract (CST) has a complex and long trajectory that originates in the cerebral cortex and ends in the spinal cord. Semaphorin 6A (Sema6A), a member of the semaphorin family, is an important regulator of CST axon guidance. Previous studies have shown that postnatalSema6Amutant mice have CST defects at the midbrain–hindbrain boundary and medulla. However, the routes the aberrant fibers take throughout theSema6Amutant brain remain unknown. In this study, we performed 3D reconstruction of immunostained CST fibers to reevaluate the details of the abnormal CST trajectories in the brains of adultSema6Amutant mice. Our results showed that the axon guidance defects reported in early postnatal mutants were consistently observed in adulthood. Those abnormal trajectories revealed by 3D analysis of brain sections were, however, more complex and variable than previously thought. In addition, 3D analysis allowed us to identify a few new patterns of aberrant projections. First, a subset of fibers that separated from and descended in parallel to the main bundle projected laterally at the caudal pons, subsequently changed direction by turning caudally, and extended to the medulla. Second, some abnormal fibers returned to the correct trajectory after deviating substantially from the original tract. Third, some fibers reached the pyramidal decussation normally but did not enter the dorsal funiculus. Section immunostaining combined with 3D reconstruction is a powerful method to track long projection fibers and to examine the entire nerve tracts of both normal and abnormal animals.