Transcriptomic and anatomic parcellation of 5-HT3AR expressing cortical interneuron subtypes revealed by single-cell RNA sequencing

Sarah Frazer; Julien Prados; Mathieu Niquille; Christelle Cadilhac; Foivos Markopoulos; Lucia Gomez; Ugo Tomasello; Ludovic Telley; Anthony Holtmaat; Denis Jabaudon; Alexandre Dayer

doi:10.1038/ncomms14219

Transcriptomic and anatomic parcellation of 5-HT_3AR expressing cortical interneuron subtypes revealed by single-cell RNA sequencing

Nat Commun. 2017 Jan 30:8:14219. doi: 10.1038/ncomms14219.

Authors

Sarah Frazer^{1

2}, Julien Prados^{1

2}, Mathieu Niquille^{1

2}, Christelle Cadilhac^{1

2}, Foivos Markopoulos², Lucia Gomez^{1

2}, Ugo Tomasello^{1

2}, Ludovic Telley², Anthony Holtmaat², Denis Jabaudon², Alexandre Dayer^{1

2}

Affiliations

¹ Department of Psychiatry, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.
² Department of Basic Neurosciences, University of Geneva Medical School, Geneva 4 CH-1211, Switzerland.

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-HT_3AR) 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-HT_3AR-containing interstitial interneurons and demonstrates that the transcriptional and anatomical parcellation of cortical interneurons is developmentally coupled.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers
COUP Transcription Factor II / metabolism
Cell Adhesion Molecules, Neuronal / metabolism
Cerebral Cortex / anatomy & histology
Cerebral Cortex / cytology
Cerebral Cortex / growth & development*
Embryo, Mammalian
Extracellular Matrix Proteins / metabolism
Female
GABAergic Neurons / physiology*
Gene Expression Profiling / methods
Gene Expression Regulation, Developmental / physiology*
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Homeodomain Proteins / physiology*
Interneurons / physiology*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microfluidics / methods
Nerve Net / growth & development
Nerve Tissue Proteins / metabolism
Receptors, Serotonin, 5-HT3 / metabolism
Reelin Protein
Sequence Analysis, RNA / methods
Serine Endopeptidases / metabolism
Single-Cell Analysis / methods

Substances

Biomarkers
COUP Transcription Factor II
Cell Adhesion Molecules, Neuronal
Extracellular Matrix Proteins
Homeodomain Proteins
Htr3a protein, mouse
Mrg1 protein, mouse
Nerve Tissue Proteins
Nr2f2 protein, mouse
Receptors, Serotonin, 5-HT3
Reelin Protein
Green Fluorescent Proteins
Serine Endopeptidases