01603nas a2200217   4500000000100000000000100001008004100002260001500043653002200058653002600080653001700106653001500123100002100138700002300159700002100182245006500203856005500268300000900323520103900332022001401371       2024                            d  c2024-12-1210aBiological models10aMechanisms of disease10aNeurogenesis10aStem cells1 aMarcella Birtele1 aMadeline Lancaster1 aGiorgia Quadrato00aModelling human brain development and disease with organoids  uhttps://www.nature.com/articles/s41580-024-00804-1  a1-243 aOrganoids are systems derived from pluripotent stem cells at the interface between traditional monolayer cultures and in vivo animal models. The structural and functional characteristics of organoids enable the modelling of early stages of brain development in a physiologically relevant 3D environment. Moreover, organoids constitute a tool with which to analyse how individual genetic variation contributes to the susceptibility and progression of neurodevelopmental disorders. This Roadmap article describes the features of brain organoids, focusing on the neocortex, and their advantages and limitations — in comparison with other model systems — for the study of brain development, evolution and disease. We highlight avenues for enhancing the physiological relevance of brain organoids by integrating bioengineering techniques and unbiased high-throughput analyses, and discuss future applications. As organoids advance in mimicking human brain functions, we address the ethical and societal implications of this technology.  a1471-0080