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

The Transcription Factors COUP-TFI and COUP-TFII have Distinct Roles in Arealisation and GABAergic Interneuron Specification in the Early Human Fetal Telencephalon.
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DOI:
10.1093/cercor/bhx185
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发表时间:
2017-10-01
期刊:
Cerebral cortex (New York, N.Y. : 1991)
影响因子:
--
通讯作者:
Clowry GJ
Clowry GJ
中科院分区:
其他
文献类型:
--
作者:
Alzu'bi A;Lindsay SJ;Harkin LF;McIntyre J;Lisgo SN;Clowry GJ

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在人端脑在8-12周postconceptibility,核糖核酸定量测序和免疫组化显示皮质鸡卵清蛋白上游启动子转录因子1(COUP-TFI)的表达在一个高的腹后低前梯度,除了提高免疫反应性在前腹侧腭。与小鼠不同,COUP-TFI和SP 8在背侧感觉新皮层和背侧海马中广泛共表达,而COUPTFI/COUPTFII共表达定义了腹侧颞叶皮层和腹侧海马。在神经节隆起(GEs)中,COUP-TFI免疫反应可区分尾侧GE(CGE)、背内侧GE(MGE)、MGE/外侧GE(LGE)边界和腹侧LGE的增殖区,而COUP-TFII仅限于腹侧CGE和MGE/LGE边界。与γ-氨基丁酸能中间神经元标记物的共标记揭示了COUP-TFI在MGE衍生的(SOX 6+)或CGE衍生的(钙视网膜蛋白+/SP 8+)中间神经元的亚群中表达。COUP-TFII主要局限于CGE衍生的中间神经元。COUP-TFI共标记的GAD 67+皮质细胞是COUP-TFII的两倍。五分之一的COUP-TFI细胞也共表达COUP-TFII,并且表达任一转录因子的细胞遵循后或前外侧通路进入皮质,因此,未观察到根据小鼠中提出的COUP-TF表达的迁移通路的分离。在从分离的人皮质祖细胞分化的培养物中,许多细胞表达COUP-TF,30%还共表达GABA,但是没有细胞表达NKX2.1。这表明中间神经元可以从表达COUP-TF的祖细胞在皮质内产生。
In human telencephalon at 8–12 postconceptional weeks, ribonucleic acid quantitative sequencing and immunohistochemistry 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 ventral pallium. Unlike in mouse, COUP-TFI and SP8 were extensively co-expressed in dorsal sensory neocortex and dorsal hippocampus whereas COUPTFI/COUPTFII co-expression defined ventral temporal cortex and ventral hippocampus. In the ganglionic eminences (GEs) COUP-TFI immunoreactivity demarcated the proliferative zones of caudal GE (CGE), dorsal medial GE (MGE), MGE/lateral GE (LGE) boundary, and ventral LGE whereas COUP-TFII was limited to ventral CGE and the MGE/LGE boundary. Co-labeling with gamma amino butyric acidergic interneuron markers revealed that COUP-TFI was expressed in subpopulations of either MGE-derived (SOX6+) or CGE-derived (calretinin+/SP8+) interneurons. COUP-TFII was mainly confined to CGE-derived interneurons. Twice as many GAD67+ cortical cells co-labeled for COUP-TFI than for COUP-TFII. A fifth of COUP-TFI cells also co-expressed COUP-TFII, and cells expressing either transcription factor followed posterior or anterio-lateral pathways into the cortex, therefore, a segregation of migration pathways according to COUP-TF expression 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 suggests interneurons could be generated intracortically from progenitors expressing either COUP-TF.
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