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

Distinct cortical and sub-cortical neurogenic domains for GABAergic interneuron precursor transcription factors NKX2.1, OLIG2 and COUP-TFII in early fetal human telencephalon.
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DOI:
10.1007/s00429-016-1343-5
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发表时间:
2017-07
影响因子:
3.1
通讯作者:
Clowry GJ
Clowry GJ
中科院分区:
医学3区
文献类型:
--
作者:
Alzu'bi A;Lindsay S;Kerwin J;Looi SJ;Khalil F;Clowry GJ

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啮齿类动物和灵长类动物端脑皮质GABA能中间神经元产生的相似性和差异性仍然存在争议。我们研究了三个中间神经元前体转录因子的表达,以及其他标志物,使用免疫组化8-12周后的概念(PCW)的人端脑切片。NKX2.1,OLIG 2和COUP-TFII表达占据了不同的(虽然重叠)神经源性结构域,这些结构域延伸到皮质,并揭示了三个CGE隔室:外侧,内侧和腹侧。NKX2.1表达在很大程度上局限于MGE,内侧CGE和腹侧隔膜,这证实了在这个发育阶段,从NKX2.1+前体产生中间神经元与啮齿动物中观察到的过程非常相似。在MGE和隔的增殖区的GABA能细胞中观察到OLIG 2免疫反应性,但不一定与NKX2.1共表达,并且在LGE、CGE和皮质中也广泛观察到OLIG 2表达。在8 PCW时,OLIG 2+细胞仅存在于内侧和前皮质壁中,表明中间神经元前体通过隔膜进入内侧皮质的迁移途径。到12 PCW时,整个皮质中存在OLIG 2+细胞,许多细胞正在积极分裂,但没有共表达皮质祖细胞标记物。分裂的COUP-TFII+祖细胞如前所述定位于腹侧CGE,但在相邻的腹侧皮质中也有大量;在这两种情况下,COUP-TFII与增殖区中的PAX 6和有丝分裂后皮质神经元中的TBR 1或钙视黄蛋白共表达。因此,COUP-TFII+祖细胞产生锥体细胞,但也产生中间神经元,其不仅从腹侧CGE向后迁移到皮质,而且还通过LGE向前迁移。本文的在线版本(doi:10.1007/s 00429 -016-1343-5)包含补充材料,可供授权用户使用。
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. The online version of this article (doi:10.1007/s00429-016-1343-5) contains supplementary material, which is available to authorized users.
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