Cerebral organoids recapitulate interneuron chain migration in the human cortex
Year: 2026
Type: preprint
Abstract: The human brain is incomplete at birth, with streams of late-born interneurons migrating into the postnatal cortex. This process is absent in rodents, limiting mechanistic investigation to post-mortem tissue. Here, we show that human cerebral organoids cultured for over six months recapitulate postnatal interneuron migration, enabling its mechanistic and genetic dissection. Live imaging and mathematical modeling revealed that interneurons intrinsically migrate in chains, while astrocyte interactions promote stream organization. Spatial and single-cell transcriptomics identified a distinct molecular signature of human postnatal migratory streams enriched for neurodevelopmental disorder-associated genes. Perturbation of the autism-associated genes CNTN5 and FGF14 differentially disrupted chain organization and migration. Thus, long-term cerebral organoids enable mechanistic analysis of previously inaccessible aspects of postnatal human brain development and their contributions to neurodevelopmental disease.
Institutions: Institute of Molecular Biotechnology, University of Vienna, Austrian Academy of Sciences, Vienna Biocenter, Medical University of Vienna, University of Graz, Universitat de València, Hospital Universitari i Politècnic La Fe, Fundacio Investigacio Hospital General Universitari De Valencia, Hospital General Universitario De Valencia
Language: English
Subfield: Developmental Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7215131885