Developmental emergence of cortical neurogliaform cell diversity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA936871 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23888400.fastq.gz | Fastqsanger.gz | |||
| SRR23888500.fastq.gz | Fastqsanger.gz | |||
| SRR23888600.fastq.gz | Fastqsanger.gz | |||
| SRR23888700.fastq.gz | Fastqsanger.gz | |||
| SRR23888800.fastq.gz | Fastqsanger.gz |
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Project description:GABAergic interneurons play crucial roles in the regulation of neural circuit activity in the cerebral cortex. A hallmark of cortical interneurons is their remarkable structural and functional diversity, yet the molecular determinants and the precise timing underlying their diversification remain largely unknown. Here we use single-cell transcriptomics to identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors define temporally and spatially restricted transcriptional trajectories that unambiguously relate to specific classes of interneurons in the adult cerebral cortex. Our findings therefore suggest that interneuron diversity is already patent shortly after neurons become postmitotic through the acquisition of specific transcriptional programs that unfold over several weeks in the developing cortex
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Project description:GABAergic interneurons are key regulators of cortical circuit function. Among the dozens of reported transcriptionally distinct subtypes of cortical interneurons, neurogliaform cells (NGCs) are unique: they are recruited by long-range excitatory inputs, are a source of slow cortical inhibition and are able to modulate the activity of large neuronal populations. Despite their functional relevance, the developmental emergence and diversity of NGCs remains unclear. Here, by combining single-cell transcriptomics, genetic fate mapping, and electrophysiological and morphological characterization, we reveal that discrete molecular subtypes of NGCs, with distinctive anatomical and molecular profiles, populate the mouse neocortex. Furthermore, we show that NGC subtypes emerge gradually through development, as incipient discriminant molecular signatures are apparent in preoptic area (POA)-born NGC precursors. By identifying NGC developmentally conserved transcriptional programs, we report that the transcription factor Tox2 constitutes an identity hallmark across NGC subtypes. Using CRISPR-Cas9-mediated genetic loss of function, we show that Tox2 is essential for NGC development: POA-born cells lacking Tox2 fail to differentiate into NGCs. Together, these results reveal that NGCs are born from a spatially restricted pool of Tox2+ POA precursors, after which intra-type diverging molecular programs are gradually acquired post-mitotically and result in functionally and molecularly discrete NGC cortical subtypes.
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