Brain development is an extraordinarily complex process achieved through the spatially and temporally regulated release of key patterning factors. In vitro neurodevelopmental models seek to mimic these processes to recapitulate the steps of tissue fate acquisition and morphogenesis. Classic two-dimensional neural cultures present higher homogeneity but lower complexity compared to the brain. Brain organoids instead have more advanced cell composition, maturation and tissue architecture. They can thus be considered at the interface of in vitro and in vivo neurobiology, and further improvements in organoid techniques are continuing to narrow the gap with in vivo brain development. Here we describe these efforts to recapitulate brain development in neural organoids and focus on their applicability for disease modeling, evolutionary studies and neural network research.
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The authors thank members of the Lancaster lab for helpful discussions. Work in the Lancaster lab is supported by the Medical Research Council (MC_UP_1201/9) and the European Research Council (ERC STG 757710).
M.A.L. is an inventor on several brain organoid patents, as well as co-founder and scientific advisor of a:head bio AG.
Peer review information Nature Neuroscience thanks Ali Brivanlou and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Chiaradia, I., Lancaster, M.A. Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo. Nat Neurosci 23, 1496–1508 (2020). https://doi.org/10.1038/s41593-020-00730-3