MTG8 interacts with LHX6 to specify cortical interneuron subtype identity

Zeinab Asgarian, Marcio Guiomar Oliveira, Agata Stryjewska, Ioannis Maragkos, Anna Noren Rubin, Lorenza Magno, Vassilis Pachnis, Mohammadmersad Ghorbani, Scott Wayne Hiebert, Myrto Denaxa and Nicoletta Kessaris ()
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Zeinab Asgarian: University College London
Marcio Guiomar Oliveira: University College London
Agata Stryjewska: University College London
Ioannis Maragkos: Biomedical Sciences Research Center “Alexander Fleming”
Anna Noren Rubin: University College London
Lorenza Magno: University College London
Vassilis Pachnis: The Francis Crick Institute
Mohammadmersad Ghorbani: University of Southampton, Southampton General Hospital
Scott Wayne Hiebert: Vanderbilt University School of Medicine
Myrto Denaxa: Biomedical Sciences Research Center “Alexander Fleming”
Nicoletta Kessaris: University College London

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Cortical interneurons originating in the embryonic medial ganglionic eminence (MGE) diverge into a range of different subtypes found in the adult mouse cerebral cortex. The mechanisms underlying this divergence and the timing when subtype identity is set up remain unclear. We identify the highly conserved transcriptional co-factor MTG8 as being pivotal in the development of a large subset of MGE cortical interneurons that co-expresses Somatostatin (SST) and Neuropeptide Y (NPY). MTG8 interacts with the pan-MGE transcription factor LHX6 and together the two factors are sufficient to promote expression of critical cortical interneuron subtype identity genes. The SST-NPY cortical interneuron fate is initiated early, well before interneurons migrate into the cortex, demonstrating an early onset specification program. Our findings suggest that transcriptional co-factors and modifiers of generic lineage specification programs may hold the key to the emergence of cortical interneuron heterogeneity from the embryonic telencephalic germinal zones.

Date: 2022
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DOI: 10.1038/s41467-022-32898-6

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