---
_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'
...