Developmental diversification of cortical inhibitory interneurons

By Christian Mayer, Christoph Hafemeister, Rachel C. Bandler, R. Machold, Kathryn C. Allaway, X. Jaglin, Renata Batista Brito, Andrew W. Butler, G. Fishell, Rahul Satija. Nature, 2017

431 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/7450ce01a65bcf74dd0dabd3df9b6cf350b4401b

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In Molecular Biology

Citations in the corpus

Comprehensive integration of single-cell data (2018, background): “While few validated regulators that drive speciﬁc interneuron fate decisions are known, we have previously shown that the transcription factor Mef2c is upregulated in embryonic precursors of PV interneurons and is speciﬁcally required for their development (Mayer et al., 2018).”
Comprehensive analysis of retinal development at single cell resolution identifies NFI factors as essential for mitotic exit and specification of late-born cells (2018, background): “The authors would like to few thousand cells, usually at a relatively smaller number of developmental ages (La Manno et al., 2016; Mayer et al., 2018; Nowakowski et al., 2017; Zhong et al., 2018), and thus do not fully capture the transcriptional changes associated with the initiation of neurogenesi”
Current best practices in single‐cell RNA‐seq analysis: a tutorial (2019, methodology): “Popular platforms such as Seurat (Butler et al , 2018), Scater (McCarthy et al , 2017), or Scanpy (Wolf et al , 2018) provide integrated environments to develop pipelines and contain large analysis toolboxes.”
The single cell transcriptional landscape of mammalian organogenesis (2019, positive): “For example, scRNA-seq recently revealed remarkable heterogeneity in neurons and myocardiocytes during mouse development 8,9 .”