In humans, execution of unimanual movements requires lateralized activation of the primary motor cortex, which then transmits the motor command to the contralateral hand through the crossed corticospinal tract (CST). Mutations in NTN1 alter motor control lateralization, leading to congenital mirror movements. To address the role of midline Netrin-1 on CST development and subsequent motor control, we analyze the morphological and functional consequences of floor plate Netrin-1 depletion in conditional knockout mice. We show that depletion of floor plate Netrin-1 in the brainstem critically disrupts CST midline crossing, whereas the other commissural systems are preserved. The only associated defect is an abnormal entry of CST axons within the inferior olive. Alteration of CST midline crossing results in functional ipsilateral projections and is associated with abnormal symmetric movements. Our study reveals the role of Netrin-1 in CST development and describes a mouse model recapitulating the characteristics of human congenital mirror movements.

在人类中，单手运动的执行需要初级运动皮层的横向激活，然后通过交叉皮质脊髓束 (CST) 将运动命令传递给对侧手。NTN1中的突变改变运动控制偏侧化，导致先天性镜子运动。为了解决中线 Netrin-1 在 CST 发育和随后的运动控制中的作用，我们分析了条件性敲除小鼠中底板 Netrin-1 耗尽的形态和功能后果。我们表明，脑干中底板 Netrin-1 的消耗严重破坏了 CST 中线交叉，而其他连合系统被保留。唯一相关的缺陷是下橄榄内 CST 轴突的异常进入。CST 中线交叉的改变导致功能性同侧投影并与异常对称运动有关。我们的研究揭示了 Netrin-1 在 CST 发育中的作用，并描述了一个重现人类先天性镜像运动特征的小鼠模型。