The generation and properties of human cortical organoids as a disease model for malformations of cortical development

As three-dimensional "organ-like" aggregates, human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of human-specificity, fidelity and manipulation. Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular, cellular, structural, and functional levels, including the anatomy, functional neural network, and interaction among different brain regions, thus facilitating the discovery of brain development and evolution. In addition to studying the neuro-electrophysiological features of brain cortex development, human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease, especially in mimicking malformations of cortical development, thus revealing pathological mechanism and identifying effective drugs. In this review, we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype, underlying mechanisms and rescue strategies.