Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013, Paris, France.
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005, Paris, France.
Sci Rep. 2017 Mar 24;7(1):410. doi: 10.1038/s41598-017-00514-z.
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.
DCC 是 NETRIN-1 受体，被认为是中枢神经系统中许多连合群的中线导向的细胞自主调节剂。皮质脊髓束 (CST) 是用于自主运动的主要运动通路，在锥体交叉处穿过解剖学中线。在表达截断 DCC 蛋白的 Kang 鼠中，CST 未能穿过中线。携带杂合性 DCC 突变的人类患有先天性镜像运动 (CMM)。由于 CMM 在某些情况下与锥体交叉的畸形有关，因此 DCC 也可能参与人类的这一过程。在这里，我们研究了 DCC 在人类和小鼠中线 CST 交叉中的作用。首先，我们通过多模态方法证明，由于 DCC 突变导致 CMM 的患者同侧 CST 投射的比例增加。其次，我们表明与 Kang 鼠不同，在 CST 中删除 DCC 的小鼠中 CST 的解剖结构没有改变。总而言之，这些结果表明 DCC 控制着人类和小鼠中线 CST 交叉，并且在小鼠中该过程是非细胞自主的。我们的数据揭示了 DCC 在 CST 中线导向中的作用的新复杂性。
