Application of brain organoids in neurodevelopmental disorders.

Understanding the etiology of human neurological and psychiatric disorders remains challenging due to species-specific genomic architectures, prolonged developmental timelines, and the unique cytoarchitectural features of the human brain, which are inadequately replicated in conventional animal models. To address these limitations, human pluripotent stem cell (hPSC)-derived brain organoids have emerged as an ethically accessible experimental system that recapitulates critical aspects of early human neurodevelopment in vitro. These three-dimensional (3D) models mimic the generation of neural progenitors, their proliferation and differentiation into neurons and glial cells, as well as the dynamic cell-cell interactions that govern cortical lamination and circuit assembly. Recent advancements in organoid culture protocols-including the fusion of region-specific brain organoids, vascularization strategies, and the incorporation of microglia-have yielded more physiologically relevant models. Such innovations enable the development of powerful bioassays to investigate disease mechanisms underlying neurodevelopmental disorders (NDDs). Despite persistent challenges related to functional synaptic maturation and modeling the blood-brain barrier, the integration of single-cell multiomics,organoid-on-a-chip systems,and xenotransplantation approaches holds promise for unraveling human-specific pathophysiology and accelerating therapeutic discovery.This review synthesizes the progress in brain organoid technologies and highlights their potential to deepen mechanistic insights into brain disorders while advancing translational research.