The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain

The COUP-TFII/Neuropilin-2 is a molecular switch steering diencephalon-derived GABAergic neurons in the developing mouse brain
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DOI:
10.1073/pnas.1420701112
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发表时间:
2015-09-08
影响因子:
11.1
通讯作者:
Nakajima, Kazunori
Nakajima, Kazunori
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kanatani, Shigeaki;Honda, Takao;Nakajima, Kazunori

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在发育中的小鼠大脑中,间脑吻侧视前区(POa)为新皮层和杏仁核提供gaba能神经元。然而,决定poa衍生神经元的途径和目的地的分子机制尚未确定。本研究表明,鸡卵白蛋白上游启动子转录因子II (COUP-TFII)诱导Neuropilin-2 (Nrp2)的表达及其下调控制了poa来源的gaba能神经元的目的地。最初,大多数poa来源的迁移神经元表达COUP-TFII,并形成一个向尾侧皮层下的尾侧迁移流。当细胞亚群转向新皮层时,它们表现出COUP-TFII和Nrp2的表达降低。目前的研究结果表明,抑制COUP-TFII/Nrp2使细胞的目的地改变为新皮层,而过表达COUP-TFII/Nrp2使细胞最终到达杏仁核的内侧。综上所述,这些结果表明,COUP-TFII/Nrp2是一个分子开关,决定了POa中出生的gaba能神经元迁移的途径和目的地。
The preoptic area (POa) of the rostral diencephalon supplies the neocortex and the amygdala with GABAergic neurons in the developing mouse brain. However, the molecular mechanisms that determine the pathway and destinations of POa-derived neurons have not yet been identified. Here we show that Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII)-induced expression of Neuropilin-2 (Nrp2) and its down-regulation control the destination of POa-derived GABAergic neurons. Initially, a majority of the POa-derived migrating neurons express COUP-TFII and form a caudal migratory stream toward the caudal subpallium. When a subpopulation of cells steers toward the neocortex, they exhibit decreased expression of COUP-TFII and Nrp2. The present findings show that suppression of COUP-TFII/Nrp2 changed the destination of the cells into the neocortex, whereas overexpression of COUP-TFII/Nrp2 caused cells to end up in the medial part of the amygdala. Taken together, these results reveal that COUP-TFII/Nrp2 is a molecular switch determining the pathway and destination of migrating GABAergic neurons born in the POa.