The early fetal development of human neocortical GABAergic interneurons.

The early fetal development of human neocortical GABAergic interneurons.
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DOI:
10.1093/cercor/bht254
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发表时间:
2015-03
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:
Al-Jaberi N;Lindsay S;Sarma S;Bayatti N;Clowry GJ

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GABA能中间神经元对控制皮层回路的兴奋性和反应性至关重要。它们的发育起源在啮齿动物和人类之间可能不同。我们用定量RT-PCR方法证实了12个GABA能中间神经元相关基因在妊娠8-12周(PCW)的人新皮质样本中的表达,并通过GAD1和2、DLX1、2和5、ASCL1、OLIG2和CALB2的原位杂交或免疫组织化学证实了明显的前后部表达梯度。皮质板(CP)形成后8~9PCW,部分细胞在CP和前板呈强阳性染色。ASCL1和DLX2在增殖区保持高表达,并与细胞分裂标记Ki-67进行广泛的免疫荧光双标。从10PCW开始,SVZ/VZ内CALB2阳性细胞逐渐增多,但未见Ki-67双标。GABA能基因在大脑皮层背侧的表达普遍高于神经节隆起,而在中间的腹侧大脑皮层的表达较低。人们普遍认为,皮质增殖区可以在妊娠中期产生CALB2阳性的中间神经元;我们现在发现,尤其是新皮质前部增殖层可能是新皮质早期中间神经元的丰富来源。
GABAergic interneurons are crucial to controlling the excitability and responsiveness of cortical circuitry. Their developmental origin may differ between rodents and human. We have demonstrated the expression of 12 GABAergic interneuron-associated genes in samples from human neocortex by quantitative rtPCR from 8 to 12 postconceptional weeks (PCW) and shown a significant anterior to posterior expression gradient, confirmed by in situ hybridization or immunohistochemistry for GAD1 and 2, DLX1, 2, and 5, ASCL1, OLIG2, and CALB2. Following cortical plate (CP) formation from 8 to 9 PCW, a proportion of cells were strongly stained for all these markers in the CP and presubplate. ASCL1 and DLX2 maintained high expression in the proliferative zones and showed extensive immunofluorescent double-labeling with the cell division marker Ki-67. CALB2-positive cells increased steadily in the SVZ/VZ from 10 PCW but were not double-labeled with Ki-67. Expression of GABAergic genes was generally higher in the dorsal pallium than in the ganglionic eminences, with lower expression in the intervening ventral pallium. It is widely accepted that the cortical proliferative zones may generate CALB2-positive interneurons from mid-gestation; we now show that the anterior neocortical proliferative layers especially may be a rich source of interneurons in the early neocortex.
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