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Nkx6.1 同源域转录因子对少突胶质细胞基因(Olig)表达及少突胶质细胞生成的区域特异性和阶段依赖性调控

Region-specific and stage-dependent regulation of Olig gene expression and oligodendrogenesis by Nkx6.1 homeodomain transcription factor.

作者信息

Liu Rugao, Cai Jun, Hu Xuemei, Tan Min, Qi Yingchuan, German Michael, Rubenstein John, Sander Maike, Qiu Mengsheng

机构信息

Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, KY 40292, USA.

出版信息

Development. 2003 Dec;130(25):6221-31. doi: 10.1242/dev.00868. Epub 2003 Nov 5.

Abstract

During early neural development, the Nkx6.1 homeodomain neural progenitor gene is specifically expressed in the ventral neural tube, and its activity is required for motoneuron generation in the spinal cord. We report that Nkx6.1 also controls oligodendrocyte development in the developing spinal cord, possibly by regulating Olig gene expression in the ventral neuroepithelium. In Nkx6.1 mutant spinal cords, expression of Olig2 in the motoneuron progenitor domain is diminished, and the generation and differentiation of oligodendrocytes are significantly delayed and reduced. The regulation of Olig gene expression by Nkx6.1 is stage dependent, as ectopic expression of Nkx6.1 in embryonic chicken spinal cord results in an induction of Olig2 expression at early stages, but an inhibition at later stages. Moreover, the regulation of Olig gene expression and oligodendrogenesis by Nkx6.1 also appears to be region specific. In the hindbrain, unlike in the spinal cord, Olig1 and Olig2 can be expressed both inside and outside the Nkx6.1-expressing domains and oligodendrogenesis in this region is not dependent on Nkx6.1 activity.

摘要

在神经发育早期,Nkx6.1同源结构域神经祖细胞基因在腹侧神经管中特异性表达,其活性是脊髓中运动神经元生成所必需的。我们报告称,Nkx6.1还可能通过调节腹侧神经上皮中的Olig基因表达来控制发育中的脊髓少突胶质细胞的发育。在Nkx6.1突变的脊髓中,运动神经元祖细胞结构域中Olig2的表达减少,少突胶质细胞的生成和分化明显延迟且减少。Nkx6.1对Olig基因表达的调控具有阶段依赖性,因为在胚胎鸡脊髓中异位表达Nkx6.1会在早期诱导Olig2表达,但在后期则会抑制其表达。此外,Nkx6.1对Olig基因表达和少突胶质细胞生成的调控似乎也具有区域特异性。在后脑,与脊髓不同,Olig1和Olig2可以在Nkx6.1表达结构域内外表达,并且该区域的少突胶质细胞生成不依赖于Nkx6.1的活性。

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