Developmental diversification of cortical inhibitory interneurons

Christian Mayer, Christoph Hafemeister, Rachel C. Bandler, Robert Machold, Renata Batista Brito, Xavier Jaglin, Kathryn Allaway, Andrew Butler, Gord Fishell () and Rahul Satija ()
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Christian Mayer: NYU Neuroscience Institute, Langone Medical Center
Christoph Hafemeister: New York Genome Center
Rachel C. Bandler: NYU Neuroscience Institute, Langone Medical Center
Robert Machold: NYU Neuroscience Institute, Langone Medical Center
Renata Batista Brito: NYU Neuroscience Institute, Langone Medical Center
Xavier Jaglin: NYU Neuroscience Institute, Langone Medical Center
Kathryn Allaway: NYU Neuroscience Institute, Langone Medical Center
Andrew Butler: New York Genome Center
Gord Fishell: NYU Neuroscience Institute, Langone Medical Center
Rahul Satija: New York Genome Center

Nature, 2018, vol. 555, issue 7697, 457-462

Abstract: Abstract Diverse subsets of cortical interneurons have vital roles in higher-order brain functions. To investigate how this diversity is generated, here we used single-cell RNA sequencing to profile the transcriptomes of mouse cells collected along a developmental time course. Heterogeneity within mitotic progenitors in the ganglionic eminences is driven by a highly conserved maturation trajectory, alongside eminence-specific transcription factor expression that seeds the emergence of later diversity. Upon becoming postmitotic, progenitors diverge and differentiate into transcriptionally distinct states, including an interneuron precursor state. By integrating datasets across developmental time points, we identified shared sources of transcriptomic heterogeneity between adult interneurons and their precursors, and uncovered the embryonic emergence of cardinal interneuron subtypes. Our analysis revealed that the transcription factor Mef2c, which is linked to various neuropsychiatric and neurodevelopmental disorders, delineates early precursors of parvalbumin-expressing neurons, and is essential for their development. These findings shed new light on the molecular diversification of early inhibitory precursors, and identify gene modules that may influence the specification of human interneuron subtypes.

Date: 2018
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DOI: 10.1038/nature25999

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