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EMBO J. 2017 May 15;36(10):1316-1329. doi: 10.15252/embj.201694700. Epub 2017 Mar 10.

Self-organized developmental patterning and differentiation in cerebral organoids.

Author information

1
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria.
2
MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
3
Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
4
Picower Institute for Learning and Memory, MIT, Cambridge, MA, USA.
5
Department of Chemical Engineering, MIT, Cambridge, MA, USA.
6
Department of Brain and Cognitive Sciences, MIT, Cambridge, MA, USA.
7
Broad Institute of Harvard University and MIT, Cambridge, MA, USA.
8
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Vienna, Austria juergen.knoblich@imba.oeaw.ac.at.

Abstract

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.

KEYWORDS:

development; human brain development; neurogenesis; organoid; patterning; signaling

PMID:
28283582
PMCID:
PMC5430225
DOI:
10.15252/embj.201694700
[Indexed for MEDLINE]
Free PMC Article

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