Abstract

Understanding human brain development remains challenging because animal models do not recapitulate many human-specific features, and access to developing human tissue is rare. Over the past decade, stem cell–derived 3D brain organoids have transformed this landscape by enabling controlled modeling of fate specification, cell diversification, migration, and emerging connectivity. Advances in patterning and culture now yield regionspecific cortical organoids that recapitulate key human cortical cell types, trajectories, and disease-relevant phenotypes. Yet current models still struggle to capture the cortex’s intricate architecture, long-range interactions, and extended maturation. In this review, we highlight emerging strategies to enhance cortical organoid complexity and the physiological relevance of their neural circuits.

Keywords

human brain development, cortical organoids, 3D brain organoids, stem cell