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The Transcription Factors COUP-TFI and COUP-TFII have Distinct Roles in Arealisation and GABAergic Interneuron Specification in the Early Human Fetal Telencephalon

Lookup NU author(s): Ayman Alzu'bi, Emerita Professor Susan Lindsay, Lauren Harkin, Dr Steven LisgoORCiD, Dr Gavin ClowryORCiD



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


In human telencephalon at 8–12 postconceptional weeks, ribonucleic acid quantitative sequencing andimmunohistochemistry revealed cortical chicken ovalbumin upstream promotor-transcription factor 1 (COUP-TFI)expression in a high ventro-posterior to low anterior gradient except for raised immunoreactivity in the anterior ventralpallium. Unlike in mouse, COUP-TFI and SP8 were extensively co-expressed in dorsal sensory neocortex and dorsalhippocampus whereas COUPTFI/COUPTFII co-expression defined ventral temporal cortex and ventral hippocampus. In theganglionic eminences (GEs) COUP-TFI immunoreactivity demarcated the proliferative zones of caudal GE (CGE), dorsalmedial GE (MGE), MGE/lateral GE (LGE) boundary, and ventral LGE whereas COUP-TFII was limited to ventral CGE and theMGE/LGE boundary. Co-labeling with gamma amino butyric acidergic interneuron markers revealed that COUP-TFI wasexpressed in subpopulations of either MGE-derived (SOX6+) or CGE-derived (calretinin+/SP8+) interneurons. COUP-TFII wasmainly confined to CGE-derived interneurons. Twice as many GAD67+ cortical cells co-labeled for COUP-TFI than for COUPTFII.A fifth of COUP-TFI cells also co-expressed COUP-TFII, and cells expressing either transcription factor followedposterior or anterio-lateral pathways into the cortex, therefore, a segregation of migration pathways according to COUP-TFexpression as proposed in mouse was not observed. In cultures differentiated from isolated human cortical progenitors,many cells expressed either COUP-TF and 30% also co-expressed GABA, however no cells expressed NKX2.1. This suggestsinterneurons could be generated intracortically from progenitors expressing either COUP-TF.

Publication metadata

Author(s): Alzu'bi A, Lindsay SJ, Harkin LF, McIntyre J, Lisgo SN, Clowry GJ

Publication type: Article

Publication status: Published

Journal: Cerebral Cortex

Year: 2017

Volume: 27

Issue: 10

Pages: 4971-4987

Print publication date: 01/10/2017

Online publication date: 09/08/2017

Acceptance date: 03/07/2017

Date deposited: 07/09/2017

ISSN (print): 1047-3211

ISSN (electronic): 1460-2199

Publisher: Oxford University Press


DOI: 10.1093/cercor/bhx185


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Funder referenceFunder name
099175/Z/12/ZWellcome Trust