Gressens Pierre
INSERM U676, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France.
Curr Opin Neurol. 2006 Apr;19(2):135-40. doi: 10.1097/01.wco.0000218228.73678.e1.
Neocortical neurons have to migrate from their site of production in the periventricular germinative zone or in the ganglionic eminence towards the cortical plate. Our understanding of the underlying molecular mechanisms has advanced considerably in recent years due to the identification of genes involved in human migration disorders and experimental studies. This review will highlight some of the most recent findings in the deciphering of the molecular machinery controlling neuronal migration.
Neuronal migration is a complex process which involves cytoskeletal molecules controlling the initiation of migration, leading edge extension and nucleokinesis; signalling molecules (the reelin pathway playing a central role) integrating external signals and linking them to the cytoskeleton; stop signals; and other molecular players including neurotrophins, glutamate receptors and peroxisome-derived factors. Emerging evidence supports the existence of cross-talk between these pathways.
Identifying these mechanisms has shed light on typical human neuronal migration disorders such as periventricular heterotopias (disorder of migration initiation linked to filamin), type I lissencephaly (cytoskeletal abnormality linked to Lis1, a microtubule-associated protein), double cortex syndrome (cytoskeletal abnormality linked to doublecortin, a microtubule-associated protein), or lissencephaly plus cerebellar hypoplasia (reelin defect).
新皮质神经元必须从其在脑室周围生发区或神经节隆起的产生部位迁移至皮质板。近年来，由于参与人类迁移障碍的基因的鉴定以及实验研究，我们对其潜在分子机制的理解有了显著进展。本综述将重点介绍在解读控制神经元迁移的分子机制方面的一些最新发现。
神经元迁移是一个复杂的过程，涉及控制迁移起始、前沿延伸和核运动的细胞骨架分子；整合外部信号并将其与细胞骨架相连的信号分子（瑞连蛋白通路起核心作用）；停止信号；以及其他分子参与者，包括神经营养因子、谷氨酸受体和过氧化物酶体衍生因子。新出现的证据支持这些通路之间存在相互作用。
确定这些机制有助于阐明典型的人类神经元迁移障碍，如脑室周围异位症（与细丝蛋白相关的迁移起始障碍）、I型无脑回畸形（与微管相关蛋白Lis1相关的细胞骨架异常）、双皮质综合征（与微管相关蛋白双皮质素相关的细胞骨架异常）或无脑回畸形合并小脑发育不全（瑞连蛋白缺陷）。
