COUP-TFII Is Preferentially Expressed in the Caudal Ganglionic Eminence and Is Involved in the Caudal Migratory Stream

COUP-TFII Is Preferentially Expressed in the Caudal Ganglionic Eminence and Is Involved in the Caudal Migratory Stream
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DOI:
10.1523/jneurosci.2132-08.2008
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发表时间:
2008-12-10
影响因子:
5.3
通讯作者:
Nakajima, Kazunori
Nakajima, Kazunori
中科院分区:
医学1区
文献类型:
--
作者:
Kanatani, Shigeaki;Yozu, Masato;Nakajima, Kazunori

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来自内侧神经节隆起(MGE)的皮质中间神经元相当分散地迁移到皮质中,而从尾神经节隆起(CGE)迁移出来的中间神经元主要以尾侧迁移流(CMS)的形式尾部进入大脑皮层和海马区(Yozu等人,2005)。尽管胚胎第13.5天的移植实验表明,这两个群体中的迁移细胞在对CGE环境做出反应的能力方面已经存在本质上的不同(Yozu等人,2005年),但尚不清楚CGE细胞是如何指定的,它们的迁移行为是如何确定的。在这项研究中,我们发现,尽管CGE和外侧神经节隆起(LGE)表达几乎相同的标记分子,但LGE细胞移植到CGE中时不会向尾部迁移,这表明LGE细胞与CGE细胞本质上是不同的。因此,我们比较了CGE、MGE和LGE的转录本,结果表明COUP-TFII在CGE以及CMS中的迁移中间神经元中优先表达。移植实验表明,COUP-TFII可使MGE细胞在CGE环境中向尾部迁移,而COUP-TFII基因的敲除可抑制CGE细胞的尾部迁移。这些结果表明,COUP-TFII对于CGE细胞在尾部方向的特异性迁移行为是必要的,也是充分的。因此,局部表达的转录因子以区域特异性的方式决定皮质中间神经元的迁移方向。
While the cortical interneurons derived from the medial ganglionic eminence (MGE) migrate rather diffusely into the cortex, interneurons that migrate out from the caudal ganglionic eminence (CGE) mainly move caudally into the caudal cerebral cortex and the hippocampus in the form of the caudal migratory stream (CMS) (Yozu et al., 2005). Although transplantation experiments at embryonic day 13.5 had revealed that the migrating cells in these two populations are already intrinsically different in regard to their ability to respond to the CGE environment ( Yozu et al., 2005), it is not known how the CGE cells are specified and how their migratory behavior is determined. In this study we showed that, although CGE and lateral ganglionic eminence (LGE) express almost the same marker molecules, LGE cells do not migrate caudally when transplanted into the CGE, suggesting that LGE cells are intrinsically different from CGE cells. We therefore compared the transcriptomes of the CGE, MGE, and LGE, and the results showed that COUP-TFII was expressed preferentially in the CGE as well as in the migrating interneurons in the CMS. Transplantation experiments revealed that COUP-TFII is sufficient to change the direction of MGE cell migration to caudal when transplanted into the CGE environment, and knockdown of COUP-TFII inhibited the caudal migration of the CGE cells. These results suggest that COUP-TFII is both required and sufficient for the CGE-cell-specific migratory behavior in the caudal direction. Thus, a locally expressed transcription factor determines the migratory direction of the cortical interneurons in a region-specific manner.