Developmental xenocortication using human-derived organoids in mice.

Human-derived cortical organoids transplanted into mouse brains form extensive, integrated xenocortical circuits with diverse human cell types, including layer 5 projection neurons.

• Why it matters: Studying human brain development and disease is limited by inaccessibility to human tissue; transplanting organoids into mice offers a way to observe human neural circuits in vivo.
• What they did: Researchers used a genetic approach to deplete mouse glutamatergic neurons and transplanted human cortical organoids into the neonatal cortical cavity, creating xenocortical mice with robust grafts.
• The result: The grafted human neurons integrated with mouse circuits, exhibited organized activity, and influenced behavior, enabling new avenues for studying neurodevelopment, disease modeling, and therapeutics.