Morphogen-guided neocortical organoids with anteroposterior areal identity.

Short-term morphogen exposure creates neocortical organoids with lasting anteroposterior patterning, matching prenatal human cortex signatures and enabling disease modeling.

• Why it matters: Understanding regional patterning in the human neocortex is crucial for deciphering neurodevelopmental disorders, but current organoid models lack accurate arealization, limiting insights into disease mechanisms.
• What they did: Researchers applied brief anterior or posterior morphogen treatments to generate organoids with distinct AP signaling centers, validated by spatial and single-cell RNA sequencing, revealing area-specific molecular signatures.
• The result: The resulting organoids accurately mimic human cortical regionalization and demonstrated disrupted AP expression gradients in fragile X syndrome models, advancing the study of NDDs with neuroanatomic relevance.