--- _id: '10179' abstract: - lang: eng text: 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. acknowledgement: We thank all Knoblich laboratory members for continued support and discussions. We thank the IMP/IMBA BioOptics facility, particularly Pawel Pasierbek, Alberto Moreno Cencerrado and Gerald Schmauss, the IMP/IMBA Molecular Biology Service, in particular Robert Heinen, the IMP Bioinformatics facility, in particular Thomas Burkard, the Vienna Biocenter Core Facilities (VBCF) Histopathology facility, in particular Tamara Engelmaier, and the VBCF Next Generation Sequencing Facility, notably Volodymyr Shubchynskyy and Carmen Czepe. We would also like to thank Simon Haendeler for advice on statistical analyses, Jose Guzman for discussions and assistance with slice culture setups, Oliver L. Eichmueller for discussions and assistance with microscopy, and E.H. Gustafson, S. Wolfinger, and D. Reumann for technical assistance regarding generation of cerebral organoids. This project received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie fellowship agreement Nr.707109 awarded to J.A.B. Work in J.A.K.'s laboratory is supported by the Austrian Federal Ministry of Education, Science and Research, the Austrian Academy of Sciences, the City of Vienna, a Research Program of the Austrian Science Fund FWF (SFBF78 Stem Cell, F 7803-B) and a European Research Council (ERC) Advanced Grant under the European 20 Union’s Horizon 2020 program (grant agreement no. 695642). article_number: e108714 article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Sunanjay full_name: Bajaj, Sunanjay last_name: Bajaj - first_name: Joshua A. full_name: Bagley, Joshua A. last_name: Bagley - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Abel full_name: Vertesy, Abel last_name: Vertesy - first_name: Sakurako full_name: Nagumo Wong, Sakurako last_name: Nagumo Wong - first_name: Veronica full_name: Krenn, Veronica last_name: Krenn - first_name: Julie full_name: Lévi-Strauss, Julie last_name: Lévi-Strauss - first_name: Juergen A. full_name: Knoblich, Juergen A. last_name: Knoblich citation: ama: Bajaj S, Bagley JA, Sommer CM, et al. Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. EMBO Journal. 2021;40(23). doi:10.15252/embj.2021108714 apa: Bajaj, S., Bagley, J. A., Sommer, C. M., Vertesy, A., Nagumo Wong, S., Krenn, V., … Knoblich, J. A. (2021). Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. EMBO Journal. Embo Press. https://doi.org/10.15252/embj.2021108714 chicago: Bajaj, Sunanjay, Joshua A. Bagley, Christoph M Sommer, Abel Vertesy, Sakurako Nagumo Wong, Veronica Krenn, Julie Lévi-Strauss, and Juergen A. Knoblich. “Neurotransmitter Signaling Regulates Distinct Phases of Multimodal Human Interneuron Migration.” EMBO Journal. Embo Press, 2021. https://doi.org/10.15252/embj.2021108714. ieee: S. Bajaj et al., “Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration,” EMBO Journal, vol. 40, no. 23. Embo Press, 2021. ista: Bajaj S, Bagley JA, Sommer CM, Vertesy A, Nagumo Wong S, Krenn V, Lévi-Strauss J, Knoblich JA. 2021. Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration. EMBO Journal. 40(23), e108714. mla: Bajaj, Sunanjay, et al. “Neurotransmitter Signaling Regulates Distinct Phases of Multimodal Human Interneuron Migration.” EMBO Journal, vol. 40, no. 23, e108714, Embo Press, 2021, doi:10.15252/embj.2021108714. short: S. Bajaj, J.A. Bagley, C.M. Sommer, A. Vertesy, S. Nagumo Wong, V. Krenn, J. Lévi-Strauss, J.A. Knoblich, EMBO Journal 40 (2021). date_created: 2021-10-24T22:01:34Z date_published: 2021-10-18T00:00:00Z date_updated: 2023-08-14T08:05:23Z day: '18' ddc: - '610' department: - _id: Bio doi: 10.15252/embj.2021108714 external_id: isi: - '000708012800001' pmid: - '34661293' file: - access_level: open_access checksum: 78d2d02e775322297e774f72810a41a4 content_type: application/pdf creator: alisjak date_created: 2021-12-13T14:54:14Z date_updated: 2021-12-13T14:54:14Z file_id: '10541' file_name: 2021_EMBO_Bajaj.pdf file_size: 7819881 relation: main_file success: 1 file_date_updated: 2021-12-13T14:54:14Z has_accepted_license: '1' intvolume: ' 40' isi: 1 issue: '23' language: - iso: eng month: '10' oa: 1 oa_version: Published Version pmid: 1 publication: EMBO Journal publication_identifier: eissn: - 1460-2075 issn: - 0261-4189 publication_status: published publisher: Embo Press quality_controlled: '1' scopus_import: '1' status: public title: Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 40 year: '2021' ...