Apr 26, 2017

Fused dorsal-ventral cerebral organoids model human cortical interneuron migration

BioRxiv : the Preprint Server for Biology
Joshua A BagleyJuergen A Knoblich

Abstract

Development of the forebrain involves the migration of GABAergic interneurons over long distances from ventral into dorsal regions. Although defects in interneuron migration are implicated in neuropsychiatric diseases such as Epilepsy, Autism, and Schizophrenia, model systems to study this process in humans are currently lacking. Here, we describe a method for analyzing human interneuron migration using 3D organoid culture. By fusing cerebral organoids specified toward dorsal and ventral forebrain, we generate a continuous dorsal-ventral axis. Using fluorescent reporters, we demonstrate robust directional GABAergic interneuron migration from ventral into dorsal forebrain. We describe methodology for time lapse imaging of human interneuron migration that is inhibited by the CXCR4 antagonist AMD3100. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions offer a possibility to analyze complex neurodevelopmental defects using cells from neuropsychiatric disease patients, and to test potential therapeutic compounds.

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Mentioned in this Paper

Schizophrenia
CXCR4 gene
Epilepsy
Antagonist Muscle Action
Brain
Time-Lapse Imaging
Cell Culture Techniques
Neurodevelopmental Disorders
C-X-C Motif Chemokine 12 Receptor Activity
CXCR4

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