INSERM UMR-S 839, 17 Rue du Fer à Moulin, Paris 75005, France; Sorbonne Universités, Université Pierre et Marie Curie, 4 Place Jussieu, Paris 75005, France; Institut du Fer à Moulin, 17 Rue du Fer à Moulin, Paris 75005, France.
Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France; INSERM UMR 1163, Embryology and Genetics of Congenital Malformations, France.
Semin Cell Dev Biol. 2018 Apr;76:33-75. doi: 10.1016/j.semcdb.2017.09.031. Epub 2017 Oct 11.
Cerebral cortical development involves a complex series of highly regulated steps to generate the laminated structure of the adult neocortex. Neuronal migration is a key part of this process. We provide here a detailed review of cortical malformations thought to be linked to abnormal neuronal migration. We have focused on providing updated views related to perturbed mechanisms based on the wealth of genetic information currently available, as well as the study of mutant genes in animal models. We discuss mainly type 1 lissencephaly, periventricular heterotopia, type II lissencephaly and polymicrogyria. We also discuss functional classifications such as the tubulinopathies, and emphasize how modern genetics is revealing genes mutated in atypical cases, as well as unexpected genes for classical cases. A role in neuronal migration is revealed for many mutant genes, although progenitor abnormalities also predominate, depending on the disorder. We finish by describing the advantages of human in vitro cell culture models, to examine human-specific cells and transcripts, and further mention non-genetic mechanisms leading to cortical malformations.
大脑皮层的发育涉及一系列复杂的高度调控步骤，以产生成人新皮层的层状结构。神经元迁移是这个过程的关键部分。我们在这里提供了一个详细的综述，内容是关于那些被认为与异常神经元迁移有关的皮质畸形。我们主要关注的是基于目前大量遗传信息以及对动物模型中突变基因的研究，提供与受干扰机制相关的最新观点。我们讨论了主要的无脑回畸形、脑室周围异位、II 型无脑回畸形和多小脑回畸形。我们还讨论了功能分类，如微管相关蛋白病，并强调了现代遗传学如何揭示非典型病例中突变的基因，以及经典病例中意想不到的基因。许多突变基因被揭示出在神经元迁移中起作用，尽管根据疾病的不同，祖细胞异常也占主导地位。我们最后描述了人类体外细胞培养模型的优势，以研究人类特异性细胞和转录本，并进一步提到导致皮质畸形的非遗传机制。
