title: Distinct cortical and sub-cortical neurogenic domains for GABAergic interneuron precursor transcription factors NKX2.1, OLIG2 and COUP-TFII in early fetal human telencephalon.
abstract: 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 8 PCW, 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 localized to ventral CGE as previously described but were also numerous in adjacent ventral cortex; in both the 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.
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.|Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: Ayman
authors.initials: A
authors.lastname: Alzu'bi
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne, NE1 3BZ, UK. susan.lindsay@ncl.ac.uk.
authors.forename: Susan
authors.initials: S
authors.lastname: Lindsay
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Kerwin
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.|Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: Shi Jie
authors.initials: SJ
authors.lastname: Looi
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.|Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: Fareha
authors.initials: F
authors.lastname: Khalil
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. gavin.clowry@ncl.ac.uk.
authors.forename: Gavin J
authors.identifier: http://orcid.org/0000-0002-6489-8329
authors.initials: GJ
authors.lastname: Clowry
mesh_terms: D051837:COUP Transcription Factor II / Q000378:metabolism*; D064032:Calbindin 2 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D000076104:Oligodendrocyte Transcription Factor 2 / Q000378:metabolism*; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051837:COUP Transcription Factor II; D064032:Calbindin 2; D000076104:Oligodendrocyte Transcription Factor 2; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C000614412:NKX2-1 protein, human; C405708:OLIG2 protein, human; C095569:NR2F2 protein, human
keywords: Ganglionic eminences; Inhibitory interneurons; Neurodevelopment; Neuronal fate specification; Pallium; Subpallium