Fused dorsal-ventral cerebral organoids model complex interactions between diverse brain regions
By J. Bagley, Daniel Reumann, Shan Bian, Julie Lévi-Strauss, Juergen A. Knoblich. Nature Methods, 2017
652 citations recorded by the source corpus.
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.
Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/615144a83a78b5827d3e76fecbf03cfefc17302e
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In Cellular and Molecular Neuroscience
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Citations in the corpus
- Brain organoids: advances, applications and challenges (2019, background): “…and mechanical forces, have been found to influence the complex but highly controlled process of gyrification during late human corticogenesis (Bae et al., 2014; Bayly et al., 2014; Del Toro et al., 2017; Florio et al., 2015; Nowakowski et al., 2016; Stahl et al., 2013; Zilles et al., 2013).”