Lian Gewei, Sheen Volney
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Curr Opin Pediatr. 2006 Dec;18(6):614-20. doi: 10.1097/MOP.0b013e328010542d.
The development of the cerebral cortex progresses through defined stages including neural proliferation, neuroblast migration and neuronal differentiation. Disruptions in each of these developmental stages can lead to characteristic cerebral cortical malformations. This review provides an overview of the known genetic causes of human cerebral developmental disorders and discusses the potential molecular mechanisms that contribute to these malformations.
Mutations in genes that are involved in neural proliferation give rise to microcephaly (small brain). Mutations in genes that direct the onset of neuroblast migration give rise to periventricular heterotopia (clusters of neurons along the ventricles of the brain). Mutations in genes that are required for neuroblast migration cause type I lissencephaly (smooth brain) and subcortical band heterotopia (smooth brain with a band of neurons beneath the cortex). Mutations in genes that direct migratory neurons to arrest in the cortex lead to type II lissencephaly (smooth brain with clusters of neurons along the surface of the brain).
The identification of causative genes involved in the formation of the cerebral cortex now allows for a rational approach with which to interpret the underlying mechanistic basis for many of these disorders.
大脑皮质的发育通过特定阶段进行，包括神经增殖、神经母细胞迁移和神经元分化。这些发育阶段中任何一个环节的中断都可能导致特征性的大脑皮质畸形。本综述概述了已知的人类大脑发育障碍的遗传原因，并讨论了导致这些畸形的潜在分子机制。
参与神经增殖的基因突变会导致小头畸形（小脑）。指导神经母细胞迁移开始的基因突变会导致室管膜下异位（沿脑室分布的神经元簇）。神经母细胞迁移所需的基因突变会导致I型无脑回畸形（光滑脑）和皮质下带异位（皮质下有一条神经元带的光滑脑）。指导迁移神经元在皮质中停滞的基因突变会导致II型无脑回畸形（脑表面有神经元簇的光滑脑）。
参与大脑皮质形成的致病基因的鉴定，现在使得我们能够以一种合理的方法来解释许多此类疾病的潜在机制基础。
