Peng Jimmy, Ferent Julien, Li Qingyu, Liu Mingwei, Da Silva Ronan Vinicius, Zeilhofer Hanns Ulrich, Kania Artur, Zhang Ying, Charron Frédéric
Montréal Clinical Research Institute (IRCM), Montréal, Quebec, Canada.
Department of Biology, McGill University, Montréal, Quebec, Canada.
Dev Dyn. 2018 Apr;247(4):620-629. doi: 10.1002/dvdy.24549. Epub 2018 Feb 5.
Humans with heterozygous mutations in the axon guidance receptor DCC display congenital mirror movements (MMs), which are involuntary movements of body parts, such as fingers, on one side of the body that mirror voluntary movement of the opposite side. In mice, the homozygous Dcc mutant allele causes synchronous MM-like hindlimb movements during locomotion, resulting in hopping. In both human and mice, the neuroanatomical defect responsible for the deficit in lateralized motor control remains to be elucidated.
Using the HoxB8-Cre line to specifically remove Dcc from the spinal cord, we found misrouting of commissural axons during their migration toward the floor plate, resulting in fewer axons crossing the midline. These mice also have a hopping gait, indicating that spinal cord guidance defects alone are sufficient to cause hopping.
Dcc plays a role in the development of local spinal networks to ensure proper lateralization of motor control during locomotion. Local spinal cord defects following loss of Dcc cause a hopping gait in mice and may contribute to MM in humans. Developmental Dynamics 247:620-629, 2018. © 2017 Wiley Periodicals, Inc.
轴突导向受体DCC发生杂合突变的人类表现出先天性镜像运动（MMs），即身体一侧的身体部位（如手指）出现非自主运动，这些运动与对侧的自主运动相对应。在小鼠中，纯合的Dcc突变等位基因会导致运动过程中后肢出现类似MM的同步运动，从而导致跳跃。在人类和小鼠中，导致侧向运动控制缺陷的神经解剖学缺陷仍有待阐明。
利用HoxB8-Cre系特异性地从脊髓中去除Dcc，我们发现连合轴突在向底板迁移过程中出现了路径错误，导致穿过中线的轴突减少。这些小鼠也有跳跃步态，表明仅脊髓导向缺陷就足以导致跳跃。
Dcc在局部脊髓网络的发育中发挥作用，以确保运动过程中运动控制的正确侧向化。Dcc缺失后局部脊髓缺陷会导致小鼠出现跳跃步态，可能也与人类的MM有关。《发育动力学》247:620 - 629，2018年。©2017威利期刊公司。
