Transcriptional maintenance of cortical somatostatin interneuron subtype identity during migration

Neuron. 2023 Nov 15;111(22):3590-3603.e5. doi: 10.1016/j.neuron.2023.07.018. Epub 2023 Aug 24.

Abstract

Although cardinal cortical interneuron identity is established upon cell-cycle exit, it remains unclear whether specific interneuron subtypes are pre-established, and if so, how their identity is maintained prior to circuit integration. We conditionally removed Sox6 (Sox6-cKO) in migrating somatostatin (Sst+) interneurons and assessed the effects on their mature identity. In adolescent mice, five of eight molecular Sst+ subtypes were nearly absent in the Sox6-cKO cortex without a reduction in cell number. Sox6-cKO cells displayed electrophysiological maturity and expressed genes enriched within the broad class of Sst+ interneurons. Furthermore, we could infer subtype identity prior to cortical integration (embryonic day 18.5), suggesting that the loss in subtype was due to disrupted subtype maintenance. Conversely, Sox6 removal at postnatal day 7 did not disrupt marker expression in the mature cortex. Therefore, Sox6 is necessary during migration for maintenance of Sst+ subtype identity, indicating that subtype maintenance requires active transcriptional programs.

Keywords: Martinotti cell; Sox6; cell-type maintenance; cortex; development; single-cell RNA sequencing; somatostatin interneuron; subtype identity; transcription factor.

MeSH terms

  • Animals
  • Cerebral Cortex
  • Electrophysiological Phenomena
  • Interneurons* / physiology
  • Mice
  • Parvalbumins / metabolism
  • Somatostatin* / metabolism

Substances

  • Somatostatin
  • Parvalbumins