Guarnieri Fabrizia Claudia, de Chevigny Antoine, Falace Antonio, Cardoso Carlos
Aix-Marseille University, INSERM U1249, INMED, Marseille 13009, France.
Dialogues Clin Neurosci. 2018 Dec;20(4):255-266. doi: 10.31887/DCNS.2018.20.4/ccardoso.
The development of the cerebral cortex requires complex sequential processes that have to be precisely orchestrated. The localization and timing of neuronal progenitor proliferation and of neuronal migration define the identity, laminar positioning, and specific connectivity of each single cortical neuron. Alterations at any step of this organized series of events-due to genetic mutations or environmental factors-lead to defined brain pathologies collectively known as malformations of cortical development (MCDs), which are now recognized as a leading cause of drug-resistant epilepsy and intellectual disability. In this heterogeneous group of disorders, macroscopic alterations of brain structure (eg, heterotopic nodules, small or absent gyri, double cortex) can be recognized and probably subtend a general reorganization of neuronal circuits. In this review, we provide an overview of the molecular mechanisms that are implicated in the generation of genetic MCDs associated with aberrations at various steps of neurogenesis and cortical development.
大脑皮层的发育需要复杂的连续过程，这些过程必须精确协调。神经元祖细胞增殖和神经元迁移的定位与时间决定了每个单个皮层神经元的身份、层状定位和特定连接。由于基因突变或环境因素，这一系列有组织的事件中任何一步的改变都会导致明确的脑部病变，统称为皮质发育畸形（MCDs），目前被认为是耐药性癫痫和智力残疾的主要原因。在这一异质性疾病组中，脑结构的宏观改变（如异位结节、脑回小或缺失、双皮质）可以被识别，并且可能意味着神经元回路的普遍重组。在本综述中，我们概述了与神经发生和皮层发育各个步骤异常相关的遗传性MCDs发生过程中涉及的分子机制。
