The corticospinal tract (CST) is the principal motor pathway for voluntary movements 1, 2, 3.
Our data unravel a new level of complexity in the role of DCC in CST guidance at the midline. 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. 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. First, we demonstrate by multimodal approaches, that patients with CMM due to DCC mutations have an increased proportion of ipsilateral CST projections. Here, we investigated the role of DCC in CST midline crossing both in human and mice. As CMM has been associated, in some cases, with malformations of the pyramidal decussation, DCC might also be involved in this process in human. Humans with heterozygous DCC mutations have congenital mirror movements (CMM). CST fails to cross the midline in Kanga mice expressing a truncated DCC protein. The corticospinal tract (CST), the principal motor pathway for voluntary movements, crosses the anatomic midline at the pyramidal decussation. DCC, a NETRIN-1 receptor, is considered as a cell-autonomous regulator for midline guidance of many commissural populations in the central nervous system.