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Distinct cortical and sub-cortical neurogenic domains for GABAergic interneuron precursor transcription factors NKX2.1, OLIG2 and COUP-TFII in early fetal human telencephalon.

Lookup NU author(s): Ayman Alzu'bi, Emerita Professor Susan Lindsay, Dr Janet Kerwin, Dr Gavin ClowryORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


The extent of similarities and differences between cortical GABAergic interneuron generation in rodent and primate telencephalon remains contentious. We examined expression of three interneuron precursor transcription factors, alongside other markers, using immunohistochemistry on 8-12 post-conceptional weeks (PCW) human telencephalon sections. NKX2.1, OLIG2 and COUP-TFII expression occupied distinct (although overlapping) neurogenic domains which extended into the cortex and revealed three CGE compartments: lateral, medial and ventral. NKX2.1 expression was very largely confined to the MGE, medial CGE and ventral septum confirming that, at this developmental stage, interneuron generation from NKX2.1+ precursors closely resembles the process observed in rodents. OLIG2 immunoreactivity was observed in GABAergic cells of the proliferative zones of the MGE and septum, but not necessarily co-expressed with NKX2.1, and OLIG2 expression was also extensively seen in the LGE, CGE and cortex. At 8PCW, OLIG2+ cells were only present in the medial and anterior cortical wall suggesting a migratory pathway for interneuron precursors via the septum into the medial cortex. By 12 PCW, OLIG2+ cells were present throughout the cortex and many were actively dividing but without co-expressing cortical progenitor markers. Dividing COUP-TFII+ progenitor cells were localised to ventral CGE as previously described but were also numerous in adjacent ventral cortex; in both cases COUP-TFII was co-expressed with PAX6 in proliferative zones and TBR1 or calretinin in post-mitotic cortical neurons. Thus COUP-TFII+ progenitors gave rise to pyramidal cells, but also interneurons which not only migrated posteriorly into the cortex from ventral CGE but also anteriorly via the LGE.

Publication metadata

Author(s): Alzubi A, Lindsay S, Kerwin J, Looi SJ, Khalil F, Clowry GJ

Publication type: Article

Publication status: Published

Journal: Brain Structure and Function

Year: 2017

Volume: 222

Issue: 5

Pages: 2309–2328

Print publication date: 01/07/2017

Online publication date: 30/11/2016

Acceptance date: 18/11/2016

Date deposited: 19/01/2017

ISSN (print): 1863-2653

ISSN (electronic): 1863-2661

Publisher: Springer Berlin Heidelberg


DOI: 10.1007/s00429-016-1343-5


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Funder referenceFunder name
099175/Z/12/ZWellcome Trust