Molecular diversity and migration of GABAergic neurons in the developing ventral midbrain

Dopaminergic neurons in the ventral midbrain (mDA) are surrounded by GABAergic neurons. The full extent of GABAergic neuron subtypes occupying this region and the mechanisms that underlie their development and function are largely unknown. Therefore, we performed single-cell RNA sequencing (scRNA-se...

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Bibliographic Details
Published in:	iScience Vol. 27; no. 11; p. 111239
Main Authors:	Düdükcü, Özge, Raj, Divya D.A., van de Haar, Lieke L., Grossouw, Laurens M., Linders, Louisa E., Garritsen, Oxana, Adolfs, Youri, van Kronenburg, Nicky C.H., Broekhoven, Mark H., Kapteijns, Troy H.W., Meye, Frank J., Pasterkamp, R. Jeroen
Format:	Journal Article
Language:	English
Published:	Elsevier Inc 15-11-2024 Elsevier
Subjects:	Cellular neuroscience Developmental neuroscience Molecular neuroscience Molecular neuroscience Cellular neuroscience Developmental neuroscience
Online Access:	Get full text
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Summary:	Dopaminergic neurons in the ventral midbrain (mDA) are surrounded by GABAergic neurons. The full extent of GABAergic neuron subtypes occupying this region and the mechanisms that underlie their development and function are largely unknown. Therefore, we performed single-cell RNA sequencing (scRNA-seq) of fluorescence-activated cell sorting (FACS)-isolated GABAergic neurons in the developing mouse ventral midbrain. Several distinct GABAergic neuron subtypes were identified based on transcriptomic profiles and spatially assigned to the ventral midbrain using in situ hybridization and immunohistochemistry for specific markers. A subset of GABAergic clusters that co-expressed mDA markers was studied in more detail and showed distinctive molecular, functional, and wiring properties. Finally, migration of different GABAergic neuron subtypes required netrin-1 from different cellular sources acting via distinct receptor mechanisms. Overall, our work provides insight into the heterogeneity and spatial organization of GABAergic neurons in the developing ventral midbrain and begins to dissect the mechanisms that underlie their development. [Display omitted] •scRNA-seq identifies GABAergic neuron subtypes in the developing ventral midbrain•Developing GABA-DA neurons show specific molecular, functional, and wiring properties•Netrin-1 controls the migration of several ventral midbrain GABAergic neuron subtypes•Distinct netrin-1 cellular sources and receptors underlie subtype-dependent migration Molecular neuroscience; Developmental neuroscience; Cellular neuroscience
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine (MDC), 10115, Berlin, Germany Present address: Department of Neurology, Northwestern University, Feinberg School of Medicine, IL 60611, Chicago, USA These authors contributed equally Lead contact
ISSN:	2589-0042 2589-0042
DOI:	10.1016/j.isci.2024.111239