Journal
EMBO JOURNAL
Volume 36, Issue 10, Pages 1316-1329Publisher
WILEY
DOI: 10.15252/embj.201694700
Keywords
development; human brain development; neurogenesis; organoid; patterning; signaling
Categories
Funding
- Marie Curie Postdoctoral Fellowship
- Medical Research Council [MC_UP_1201/9]
- Austrian Academy of Sciences
- Austrian Science Fund [I_1281-B19, Z_153_B09]
- European Research Council (ERC)
- Burroughs Wellcome Fund Career Awards at the Scientific Interface
- Searle Scholars Program
- Packard award in Science and Engineering
- NARSAD Young Investigator Award
- JPB Foundation (PIIF)
- JPB Foundation (PNDRF)
- NCSOFT Cultural Foundation
- NIH [1-U01-NS090473-01]
- Austrian Science Fund (FWF) [Z153] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [Z 153] Funding Source: researchfish
- Medical Research Council [MC_UP_1201/9] Funding Source: researchfish
- MRC [MC_UP_1201/9] Funding Source: UKRI
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Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia. Consistent with this, we demonstrate the presence of forebrain organizing centers that express secreted growth factors, which may be involved in dorso-ventral patterning within organoids. Furthermore, we demonstrate the timed generation of neurons with mature morphologies, as well as the subsequent generation of astrocytes and oligodendrocytes. Our work provides the methodology and quality criteria for phenotypic analysis of brain organoids and shows that the spatial and temporal patterning events governing human brain development can be recapitulated in vitro.
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