PT  - JOURNAL ARTICLE
AU  - Hermany Munguba
AU  - Kasra Nikouei
AU  - Hannah Hochgerner
AU  - Polina Oberst
AU  - Alexandra Kouznetsova
AU  - Jesper Ryge
AU  - Renata Batista-Brito
AU  - Ana Belén Munoz-Manchado
AU  - Jennie Close
AU  - Sten Linnarsson
AU  - Jens Hjerling-Leffler
TI  - Transcriptional maintenance of cortical somatostatin interneuron subtype identity during migration
AID  - 10.1101/593285
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 593285
4099  - http://biorxiv.org/content/early/2019/03/31/593285.short
4100  - http://biorxiv.org/content/early/2019/03/31/593285.full
AB  - Recent work suggests that cortical interneuron diversity arises from genetic mechanisms guided by the interplay of intrinsic developmental patterning and local extrinsic cues. Individual genetic programs underlying subtype identity are at least partly established in postmitotic neural precursors, prior to their tangential migration and integration in the cortical circuitry. Nevertheless, it is unclear how distinct interneuron identities are maintained during their migration and maturation. Sox6 is a transcription factor with an established role in MGE-derived interneuron maturation and positional identity. To determine its role in maintaining somatostatin (Sst)-expressing interneurons’ subtype identity, we conditionally removed Sox6 in migrating Sst interneurons and assessed the effects on their mature identity using single-cell RNA-sequencing (scRNAseq), in situ hybridization and electrophysiology. Sox6 removal prior to migration in Sst-expressing neurons reduced subtype diversity without affecting overall number of neurons. Seven out of nine Sst-expressing molecular subtypes were absent in the mature primary somatosensory cortex of Sox6-cKO mice, including the Chodl-Nos1-expressing type which has been shown to be specified at, or shortly after, cell cycle exit. The remaining Sst-expressing subtypes in the Sox6-cKO cortex comprised three molecular subtypes, Crh-C1ql3 and Hpse-Cbln4, and a third subtype that seemed to be a molecular hybrid of these subtypes. Moreover, Sox6-cKO cells still expressed genes enriched within the entire class of Sst-expressing neurons, such as Sst, Lhx6, Satb1, Elfn1 and Mafb. Removal of Sox6 at P7, after cells have reached their final destination and begin integration into the network, did not disrupt Chodl-Nos1 marker expression. Our findings suggest that expression of Sox6 during the migratory phase of cortical interneurons is necessary for maintenance of Sst+ subtype identity, indicating that subtype maintenance during migration requires active transcriptional programs.