Fused cerebral organoids model interactions between brain regions
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Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.
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Both studies demonstrated disruption of interneuron migration by antagonism of CXCR4.
“These findings were further supported by another report documenting interneuron migration following fusion of dorsal and ventral brain organoids26, and both studies demonstrated disruption of migration by antagonism of C-X-C chemokine receptor type 4 (CXCR4), which has an important role in interneuron migration6,26.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [26]
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- Authors
- Bagley, J. A., Reumann, D., Bian, S., Lévi-Strauss, J., & Knoblich, J. A.
- Affiliations
- Institute of Molecular Biotechnology (AT)
- Corresponding author
- Knoblich, Juergen A
- Venue
- Nature Methods
- Published
- 2017-05-10
- Volume
- 14
- Issue
- 7
- Pages
- 743-751
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC5540177
- OpenAlex
- W2612533830
- Cited by
- 790
- References
- 68
- Citations by year
- 2026: 56 · 2025: 82 · 2024: 116 · 2023: 89 · 2022: 105 · 2021: 112 · 2020: 95 · 2019: 79 · 2018: 42 · 2017: 13
- FWCI
- 26.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Methods (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Massachusetts Institute of Technology
- Österreichischen Akademie der Wissenschaften
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- brain organoids, organoid fusion, dorsal-ventral axis, CXCR4, neuronal migration, human brain development, time-lapse imaging, fluorescent reporter, iPSC reprogramming
- MeSH terms
- Animals, Brain, Cell Communication, Cell Movement, Cerebral Cortex, Humans, Interneurons, Organoids, Cell Culture Techniques
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