The study describes the development and application of cerebral organoids, a 3D culture system derived from human pluripotent stem cells, to model human brain development and microcephaly. The organoids develop various discrete brain regions, including the cerebral cortex, which contains progenitor populations that organize and produce mature cortical neuron subtypes. These organoids recapitulate key features of human cortical development, such as the characteristic progenitor zone organization and the presence of outer radial glial stem cells (oRGs). The authors used patient-derived induced pluripotent stem cells (iPSCs) and RNA interference to model microcephaly, a disorder characterized by reduced brain size. They observed premature neuronal differentiation in patient-derived organoids, which could explain the disease phenotype. The study demonstrates that 3D organoids can recapitulate the development and disease of complex human tissues, providing a valuable tool for studying neurodevelopmental processes and neurological disorders.The study describes the development and application of cerebral organoids, a 3D culture system derived from human pluripotent stem cells, to model human brain development and microcephaly. The organoids develop various discrete brain regions, including the cerebral cortex, which contains progenitor populations that organize and produce mature cortical neuron subtypes. These organoids recapitulate key features of human cortical development, such as the characteristic progenitor zone organization and the presence of outer radial glial stem cells (oRGs). The authors used patient-derived induced pluripotent stem cells (iPSCs) and RNA interference to model microcephaly, a disorder characterized by reduced brain size. They observed premature neuronal differentiation in patient-derived organoids, which could explain the disease phenotype. The study demonstrates that 3D organoids can recapitulate the development and disease of complex human tissues, providing a valuable tool for studying neurodevelopmental processes and neurological disorders.