类有机物
神经科学
生物
轴突
人脑
连接组学
斑马鱼
轴突引导
解剖
交叉
连接体
功能连接
生物化学
基因
作者
Stefano L. Giandomenico,Susanna B. Mierau,George Gibbons,Léa M. D. Wenger,Laura Masullo,Timothy Sit,Magdalena Sutcliffe,Jérôme Boulanger,Marco Tripodi,Emmanuel Derivery,Ole Paulsen,András Lakatos,Madeline A. Lancaster
标识
DOI:10.1038/s41593-019-0350-2
摘要
Neural organoids have the potential to improve our understanding of human brain development and neurological disorders. However, it remains to be seen whether these tissues can model circuit formation with functional neuronal output. Here we have adapted air-liquid interface culture to cerebral organoids, leading to improved neuronal survival and axon outgrowth. The resulting thick axon tracts display various morphologies, including long-range projection within and away from the organoid, growth-cone turning, and decussation. Single-cell RNA sequencing reveals various cortical neuronal identities, and retrograde tracing demonstrates tract morphologies that match proper molecular identities. These cultures exhibit active neuronal networks, and subcortical projecting tracts can innervate mouse spinal cord explants and evoke contractions of adjacent muscle in a manner dependent on intact organoid-derived innervating tracts. Overall, these results reveal a remarkable self-organization of corticofugal and callosal tracts with a functional output, providing new opportunities to examine relevant aspects of human CNS development and disease.
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