Cerebral organoids recapitulate interneuron chain migration in the human cortex
- 1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA)
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.
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BibTeX
@misc{wong2026cerebral,
title = {{Cerebral organoids recapitulate interneuron chain migration in the human cortex}},
author = {S. Nagumo Wong and M. A. Noble and M. Fischer and L. Meyer and M. Novatchkova and E. Novakova and D. van der Heijden and L. B. Moya and S. Gonzalez-Granero and J. M. Garcia-Verdugo and S. Merino-Aceituno and N. S. Corsini and J. A. Knoblich},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.729488},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.729488v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cerebral organoids recapitulate interneuron chain migration in the human cortex
AU - S. Nagumo Wong
AU - M. A. Noble
AU - M. Fischer
AU - L. Meyer
AU - M. Novatchkova
AU - E. Novakova
AU - D. van der Heijden
AU - L. B. Moya
AU - S. Gonzalez-Granero
AU - J. M. Garcia-Verdugo
AU - S. Merino-Aceituno
AU - N. S. Corsini
AU - J. A. Knoblich
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.729488
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.729488v1
AB - 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.
ER -