Abstract
DCC, a NETRIN-1 receptor, is considered as a cell-autonomous regulator for midline guidance of many commissural populations in the central nervous system. The corticospinal tract (CST), the principal motor pathway for voluntary movements, crosses the anatomic midline at the pyramidal decussation. CST fails to cross the midline in Kanga mice expressing a truncated DCC protein. Humans with heterozygous DCC mutations have congenital mirror movements (CMM). As CMM has been associated, in some cases, with malformations of the pyramidal decussation, DCC might also be involved in this process in human. Here, we investigated the role of DCC in CST midline crossing both in human and mice. First, we demonstrate by multimodal approaches, that patients with CMM due to DCC mutations have an increased proportion of ipsilateral CST projections. Second, we show that in contrast to Kanga mice, the anatomy of the CST is not altered in mice with a deletion of DCC in the CST. Altogether, these results indicate that DCC controls CST midline crossing in both humans and mice, and that this process is non cell-autonomous in mice. Our data unravel a new level of complexity in the role of DCC in CST guidance at the midline.
Highlights
The corticospinal tract (CST) is the principal motor pathway for voluntary movements[1,2,3]
The aim of the present paper was to study the role of DCC in CST midline crossing in both human and mice: we checked whether the role of DCC in the development of the pyramidal decussation is conserved in human and whether this process is cell-autonomous in mouse
We demonstrate that DCC deficiency is associated with abnormal CST midline crossing and a reduced ability to generate asymmetric movements in both humans and mice
Summary
The corticospinal tract (CST) is the principal motor pathway for voluntary movements[1,2,3]. The role of DCC in the development of the CST has not been investigated in Dcc−/− knockout mice They die within 24 hours after birth, when the CST crosses the midline and enter the spinal cord. These mice are characterized by a striking “kangaroo-like” hopping gait, and replicate most of the commissural defects observed in Dcc−/− mutants. Two CMM patients with initially unknown genetic status were eventually found to carry a DCC mutation, years after publication of their neurophysiological data In these two patients, unilateral transcranial magnetic stimulation (TMS) of the primary motor cortex elicited bilateral motor responses, suggesting the existence of bilateral CST projections to the spinal cord[20,21,22]. We analyzed the anatomy of the CST in various Dcc deficient mouse mutants, including a line with a conditional deletion of DCC in the neocortex (and in the CST)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
