Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements
Résumé
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 inNTN1alter motor control lateralization, leading to congenital mirror movements. Toaddress the role of midline Netrin-1 on CST development and subsequent motor control, we analyze themorphological 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 entryof CST axons within the inferior olive. Alteration of CST midline crossing results in functional ipsilateral pro-jections and is associated with abnormal symmetric movements. Our study reveals the role of Netrin-1 in CSTdevelopment and describes a mouse model recapitulating the characteristics of human congenital mirrormovements.
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