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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure.
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CNS myelin paranodes require Nkx6-2 homeoprotein transcriptional activity for normal structure.

机译:中枢神经系统髓鞘对节需要正常结构的Nkx6-2同源蛋白转录活性。

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摘要

Homeodomain proteins play critical roles during development in cell fate determination and proliferation, but few studies have defined gene regulatory networks for this class of transcription factors in differentiated cells. Using a lacZ-knock-in strategy to ablate Nkx6-2, we find that the Nkx6-2 promoter is active embryonically in neuroblasts and postnatally in oligodendrocytes. In addition to neurological deficits, we find widespread ultrastructural abnormalities in CNS white matter and aberrant expression of three genes encoding a paranodal microtubule destabilizing protein, stathmin 1, and the paranodal cell adhesion molecules neurofascin and contactin. The involvement of these downstream proteins in cytoskeletal function and cell adhesion reveals mechanisms whereby Nkx6-2 directly or indirectly regulates axon- glial interactions at myelin paranodes. Nkx6-2 does not appear to be the central regulator of axoglial junction assembly; nonetheless, our data constitute the first evidence of such a regulatory network and provide novel insights into the mechanism and effector molecules that are involved.
机译:同源结构域蛋白在发育过程中在细胞命运决定和增殖中起关键作用,但是很少有研究为分化细胞中此类转录因子定义基因调控网络。使用lacZ敲入策略消融Nkx6-2,我们发现Nkx6-2启动子在成神经细胞中具有胚胎活性,在出生后在少突胶质细胞中具有活性。除了神经系统缺陷外,我们发现中枢神经系统白质中普遍存在超微结构异常,并且三个编码旁淋巴微管失稳蛋白stathmin 1的基因的异常表达,以及旁淋巴细胞粘附分子neurofascin和contactin的异常表达。这些下游蛋白参与细胞骨架功能和细胞粘附揭示了机制,其中Nkx6-2直接或间接调节髓鞘副节的轴突相互作用。 Nkx6-2似乎不是轴突连接组件的中央调节器。尽管如此,我们的数据构成了这种调控网络的第一个证据,并为涉及的机制和效应分子提供了新颖的见解。

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