Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. (18th October 2021)

• Record Type: Journal Article
• Authors: Bajaj, Sunanjay; Bagley, Joshua A; Sommer, Christoph; Vertesy, Abel; Nagumo Wong, Sakurako; Krenn, Veronica; Lévi‐Strauss, Julie; Knoblich, Juergen A
• Is Part Of: EMBO journal. Volume 40:Number 23(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-10-18
• Subjects: cerebral organoid fusions -- cortical interneuron migration -- human brain development -- live cell imaging -- neurotransmitter signaling pathways; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2021108714
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: Inhibitory GABAergic interneurons migrate over long distances from their extracortical origin into the developing cortex. In humans, this process is uniquely slow and prolonged, and it is unclear whether guidance cues unique to humans govern the various phases of this complex developmental process. Here, we use fused cerebral organoids to identify key roles of neurotransmitter signaling pathways in guiding the migratory behavior of human cortical interneurons. We use scRNAseq to reveal expression of GABA, glutamate, glycine, and serotonin receptors along distinct maturation trajectories across interneuron migration. We develop an image analysis software package, TrackPal, to simultaneously assess 48 parameters for entire migration tracks of individual cells. By chemical screening, we show that different modes of interneuron migration depend on distinct neurotransmitter signaling pathways, linking transcriptional maturation of interneurons with their migratory behavior. Altogether, our study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by neurotransmitter signaling. SYNOPSIS: Using an interneuron‐specific reporter to track migrating cortical interneurons in human cerebral organoid fusions, this study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by diverse neurotransmitter signaling pathways. Single‐cell human GABAergic lineage reconstruction identifies neurotransmitter receptor expression in migrating human cortical interneurons. Newly developed software package, TrackPal, quantifies large‐scale, live‐imaging based tracking of migrating human cortical interneurons. Small‐molecule screening identifies divergent roles of neurotransmitter receptors in regulating intrinsic interneuron migration behavior. Neurotransmitter signaling modulates distinct modes of interneuron migration. Abstract : Live‐imaging in cerebral organoids combined with single‐cell transcriptomics and small‐molecule screening reveals distinct modes of human interneuron migration and their modulation by different neurotransmitters.