Reconstructing human corticogenesis: Insights from cerebral organoids into neurodevelopment and disease modeling.
Miguel F Tenreiro, Alysson R Muotri
Abstract
Understanding the neurodevelopmental biology of the human brain remains a major challenge, primarily due to the lack of model systems that accurately reflect the evolutionary innovations underlying human-specific cell-type diversification, cortical expansion, and higher-order cognition. Cerebral organoids have emerged as powerful stem-cell-derived systems that offer unique opportunities to investigate these processes. Here, we discuss the cellular and molecular features that define human telencephalic development, evaluate how faithfully organoid models mirror in vivo developmental programs, and explore their potential for modeling neurodevelopmental disorders and for therapeutic discovery. We also critically assess the current limitations of cerebral organoids and highlight emerging strategies to enhance their fidelity and translational utility.