Cited by 790Neurogenesis and neuroplasticity mechanismsPluripotent Stem Cells ResearchDevelopmental Biology and Gene Regulation

Fused cerebral organoids model interactions between brain regions

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Bagley, Joshua A, Reumann, Daniel, Bian, Shan, Lévi-Strauss, Julie, Knoblich, Juergen A·2017·Nature Methods

Abstract

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.”

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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
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
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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