Walsh C A
Division of Neurogenetics, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
Ment Retard Dev Disabil Res Rev. 2000;6(1):34-40. doi: 10.1002/(SICI)1098-2779(2000)6:1<34::AID-MRDD5>3.0.CO;2-Y.
The development of the cerebral cortex requires large-scale movement of neurons from areas of proliferation to areas of differentiation and adult function in the cortex proper, and the patterns of this neuronal migration are surprisingly complex. The migration of neurons is affected by several naturally occurring genetic defects in humans and mice; identification of the genes responsible for some of these conditions has recently yielded new insights into the mechanisms that regulate migration. Other key genes have been identified via the creation of induced mutations that can also cause dramatic disorders of neuronal migration. However, our understanding of the physiological and biochemical links between these genes is still relatively spotty. A number of molecules have also been studied in mice (Reelin, mDab1, and the VLDL and ApoE2 receptors) that appear to represent part of a coherent signaling pathway that regulates migration, because multiple genes cause an indistinguishable phenotype when mutated. On the other hand, two human genes that cause lissencephaly (LIS1, DCX) encode proteins that have recently been implicated as regulators or microtubule dynamics. This article reviews some of the mutant phenotypes in light of the mechanisms of neuronal migration. MRDD Research Reviews 6:34-40, 2000.
大脑皮层的发育需要神经元从增殖区域大规模迁移至分化区域以及大脑皮层固有区域的成年功能区，而且这种神经元迁移的模式极为复杂。人类和小鼠中一些自然发生的基因缺陷会影响神经元的迁移；对导致其中某些情况的基因的鉴定，最近为调节迁移的机制带来了新的见解。其他关键基因是通过产生诱导突变而鉴定出来的，这些突变也会导致神经元迁移的严重紊乱。然而，我们对这些基因之间生理和生化联系的理解仍然比较零散。在小鼠中也对一些分子（Reelin、mDab1以及极低密度脂蛋白和载脂蛋白E2受体）进行了研究，这些分子似乎代表了调节迁移的一个连贯信号通路的一部分，因为多个基因在发生突变时会导致难以区分的表型。另一方面，两个导致无脑回畸形的人类基因（LIS1、DCX）编码的蛋白质最近被认为是调节因子或参与微管动力学。本文根据神经元迁移的机制对一些突变表型进行了综述。《MRDD研究评论》6:34 - 40，2000年。
