Feng Y, Walsh C A
Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Centre, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.
Nat Rev Neurosci. 2001 Jun;2(6):408-16. doi: 10.1038/35077559.
Neuronal migration, like the migration of many cell types, requires an extensive rearrangement of cell shape, mediated by changes in the cytoskeleton. The genetic analysis of human brain malformations has identified several biochemical players in this process, including doublecortin (DCX) and LIS1, mutations of which cause a profound migratory disturbance known as lissencephaly ('smooth brain') in humans. Studies in mice have identified additional molecules such as Cdk5, P35, Reelin, Disabled and members of the LDL superfamily of receptors. Understanding the cell biology of these molecules has been a challenge, and it is not known whether they function in related biochemical pathways or in very distinct processes. The last year has seen rapid advances in the biochemical analysis of several such molecules. This analysis has revealed roles for some of these molecules in cytoskeletal regulation and has shown an unexpected conservation of the genetic pathways that regulate neuronal migration in humans and nuclear movement in simple eukaryotic organisms.
与许多细胞类型的迁移一样，神经元迁移需要细胞形状的广泛重排，这由细胞骨架的变化介导。对人类脑畸形的遗传分析已确定了这一过程中的几个生化作用因子，包括双皮质素（DCX）和LIS1，其突变在人类中会导致一种严重的迁移障碍，称为无脑回畸形（“光滑脑”）。对小鼠的研究已确定了其他分子，如Cdk5、P35、Reelin、Disabled以及低密度脂蛋白受体超家族的成员。了解这些分子的细胞生物学一直是一项挑战，目前尚不清楚它们是在相关的生化途径中发挥作用，还是在非常不同的过程中发挥作用。过去一年，对其中几种分子的生化分析取得了迅速进展。这一分析揭示了其中一些分子在细胞骨架调节中的作用，并表明在调节人类神经元迁移和简单真核生物核运动的遗传途径中存在意想不到的保守性。
