Genetic studies identified multiple mutations associated with malformations of cortical development (MCD) in humans. When analyzing the underlying mechanisms in non-human experimental models it became increasingly evident, that these mutations accumulate in genes, which functions evolutionary progressed from rodents to humans resulting in an incomplete reflection of the molecular and cellular alterations in these models. Human brain organoids derived from human pluripotent stem cells resemble early aspects of human brain development to a remarkable extent making them an attractive model to investigate MCD. Here we review how human brain organoids enable the generation of fundamental new insight about the underlying pathomechanisms of MCD. We show how phenotypic features of these diseases are reflected in human brain organoids and discuss challenges and future considerations but also limitations for the use of human brain organoids to model human brain development and associated disorders.

遗传学研究确定了与人类皮质发育畸形 (MCD) 相关的多种突变。在分析非人类实验模型中的潜在机制时，越来越明显的是，这些突变在基因中积累，其功能从啮齿动物进化到人类，导致这些模型中分子和细胞变化的不完整反映。源自人类多能干细胞的人类大脑类器官在很大程度上类似于人类大脑发育的早期方面，使其成为研究 MCD 的有吸引力的模型。在这里，我们回顾了人类大脑类器官如何能够产生关于 MCD 潜在病理机制的基本新见解。