Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo

Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causes axon pathfinding errors in vivo
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DOI:
10.1073/pnas.97.22.12318
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发表时间:
2000-10-24
影响因子:
11.1
通讯作者:
Anderson, DJ
Anderson, DJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Paquette, AJ;Perez, SE;Anderson, DJ

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神经元限制性沉默因子(NRSF;也被称为REST的阻遏元件-1沉默转录因子)是一个多个神经元基因的转录阻遏物,但很少有人知道它在体内的功能。NRSF通常在神经元分化后下调。NRSF在鸡胚胎发育脊髓中的组成性表达导致两个内源性靶基因N-微管蛋白和Ng-CAM的抑制,但并不能阻止明显的神经发生。然而,连合神经元分化,而组成性表达NRSF表现出显着增加的频率轴突导向错误。这些数据表明,下调NRSF是必要的,至少有一些类的神经元在体内的适当发展。
The neuron-restrictive silencer factor (NRSF; also known as REST for repressor element-1 silencing transcription factor) is a transcriptional repressor of multiple neuronal genes, but little is known about its function in vivo. NRSF is normally down-regulated upon neuronal differentiation. Constitutive expression of NRSF in the developing spinal cord of chicken embryos caused repression of two endogenous target genes, N-tubulin and Ng-CAM, but did not prevent overt neurogenesis. Nevertheless, commissural neurons that differentiated while constitutively expressing NRSF showed a significantly increased frequency of axon guidance errors. These data suggest that down-regulation of NRSF is necessary for the proper development of at least some classes of neurons in vivo.