title: Transcriptomic and anatomic parcellation of 5-HT3AR expressing cortical interneuron subtypes revealed by single-cell RNA sequencing.
abstract: Cortical GABAergic interneurons constitute a highly diverse population of inhibitory neurons that are key regulators of cortical microcircuit function. An important and heterogeneous group of cortical interneurons specifically expresses the serotonin receptor 3A (5-HT3AR) but how this diversity emerges during development is poorly understood. Here we use single-cell transcriptomics to identify gene expression patterns operating in Htr3a-GFP+ interneurons during early steps of cortical circuit assembly. We identify three main molecular types of Htr3a-GFP+ interneurons, each displaying distinct developmental dynamics of gene expression. The transcription factor Meis2 is specifically enriched in a type of Htr3a-GFP+ interneurons largely confined to the cortical white matter. These MEIS2-expressing interneurons appear to originate from a restricted region located at the embryonic pallial-subpallial boundary. Overall, this study identifies MEIS2 as a subclass-specific marker for 5-HT3AR-containing interstitial interneurons and demonstrates that the transcriptional and anatomical parcellation of cortical interneurons is developmentally coupled.
authors.affiliation: Department of Psychiatry, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.|Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Frazer
authors.affiliation: Department of Psychiatry, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.|Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Julien
authors.identifier: 0000-0002-8546-241X
authors.initials: J
authors.lastname: Prados
authors.affiliation: Department of Psychiatry, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.|Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Niquille
authors.affiliation: Department of Psychiatry, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.|Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Christelle
authors.initials: C
authors.lastname: Cadilhac
authors.affiliation: Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Foivos
authors.initials: F
authors.lastname: Markopoulos
authors.affiliation: Department of Psychiatry, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.|Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gomez
authors.affiliation: Department of Psychiatry, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.|Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Ugo
authors.initials: U
authors.lastname: Tomasello
authors.affiliation: Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Ludovic
authors.identifier: 0000-0002-5041-1997
authors.initials: L
authors.lastname: Telley
authors.affiliation: Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Anthony
authors.initials: A
authors.lastname: Holtmaat
authors.affiliation: Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Jabaudon
authors.affiliation: Department of Psychiatry, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.|Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dayer
mesh_terms: D000818:Animals; D015415:Biomarkers; D051837:COUP Transcription Factor II / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000166:cytology / Q000254:growth & development*; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D044085:Microfluidics / Q000379:methods; D009415:Nerve Net / Q000254:growth & development; D009419:Nerve Tissue Proteins / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D000091042:Reelin Protein; D017423:Sequence Analysis, RNA / Q000379:methods; D012697:Serine Endopeptidases / Q000378:metabolism; D059010:Single-Cell Analysis / Q000379:methods
chemical_list: D015415:Biomarkers; D051837:COUP Transcription Factor II; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; C511230:Htr3a protein, mouse; C102641:Mrg1 protein, mouse; D009419:Nerve Tissue Proteins; C497587:Nr2f2 protein, mouse; D044406:Receptors, Serotonin, 5-HT3; D000091042:Reelin Protein; D049452:Green Fluorescent Proteins; D012697:Serine Endopeptidases