Self‐organized developmental patterning and differentiation in cerebral organoids. (10th March 2017)

• Record Type: Journal Article
• Authors: Renner, Magdalena; Lancaster, Madeline A; Bian, Shan; Choi, Heejin; Ku, Taeyun; Peer, Angela; Chung, Kwanghun; Knoblich, Juergen A
• Is Part Of: EMBO journal. Volume 36:Number 10(2017)
• Page Start: 1316
• Page End: 1329
• Publication Date: 2017-03-10
• Subjects: development -- human brain development -- neurogenesis -- organoid -- patterning -- signaling; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201694700
• Languages: English
• ISSNs: 0261-4189

Abstract

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 . Synopsis: Cerebral organoids develop differentiated areas of discrete brain region identities without the addition of exogenous patterning signals. Cerebral organoids contain structures reminiscent of two forebrain organizing centers, cortical hem, and pallial–subpallial boundary, which may specify organoid regional identities. Analysis of cerebral organoid 3D structure reveals a high degree of interconnectivity within organoid tissues. Cerebral organoids generate different neuronal subtypes with mature morphologies in a timed manner. Cerebral organoids are capable of forming astrocytes and oligodendrocytes. Abstract : Cerebral organoids have the intrinsic propensity to develop into differentiated brain tissue with regions of discrete identities in the absence of exogenously added patterning signals.