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 and Alexandre Dayer ()
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Sarah Frazer: University of Geneva Medical School
Julien Prados: University of Geneva Medical School
Mathieu Niquille: University of Geneva Medical School
Christelle Cadilhac: University of Geneva Medical School
Foivos Markopoulos: University of Geneva Medical School
Lucia Gomez: University of Geneva Medical School
Ugo Tomasello: University of Geneva Medical School
Ludovic Telley: University of Geneva Medical School
Anthony Holtmaat: University of Geneva Medical School
Denis Jabaudon: University of Geneva Medical School
Alexandre Dayer: University of Geneva Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14219

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