Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor cells through bHLH proteins and Nurr1
Control of neurogenesis and tyrosine hydroxylase expression in neural progenitor cells through bHLH proteins and Nurr1
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DOI：
10.1016/j.expneurol.2006.08.029
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发表时间：
2007-02-01
影响因子：
5.3
通讯作者：
Svendsen, Clive N.
中科院分区：
文献类型：
--
作者：
Kim, Hyan-Jung;Sugimori, Michiya;Svendsen, Clive N.
神经前体细胞(NPC)的多巴胺(DA)神经元的产生尤其令人感兴趣，因为这些神经元在帕金森病中退化。在这里，我们报告了来自腹侧中脑(NPCVM)和纹状体(NPCSTR)的鼻咽癌的特征是内在决定的。对发育过程中的VM的详细分析表明，Ngn2和Mash1在DA前体结构域中表达。有趣的是，Ngn2或Mash1的过度表达诱导了扩大的NPCVM的神经发生。尽管Ngn2即使在有丝分裂原存在的情况下也会抑制细胞分裂和神经元的产生，但Mash1允许祖细胞分裂，同时保持神经发生的潜力。然而，过度表达Ngn2或Mash1的新神经元中，没有一个神经元的酪氨酸羟基酶等DA神经元标志呈阳性。NURR1的过度表达以剂量依赖的方式增加神经元和神经胶质细胞内的TH水平，这表明NURR1对该酶的激活是非神经元特异性的。Nurr1和Ngn2或Mash1的双重感染导致少量TW神经元的产生，NPCvm来源的TW神经元比NPCSTR来源的TW神经元体积大。这些数据为多种转录因子的过度表达可以推动鼻咽癌的命运首先转向神经元，然后转向DA表型的概念提供了证据。然而，可能需要更多的因素才能产生完全功能的DA神经元。(C)2006 Elsevier Inc.保留所有权利。
The production of dopamine (DA) neurons from neural progenitor cells (NPC) is of particular interest as these neurons degenerate in Parkinson's disease. Here, we report that the characteristics of NPC from the ventral midbrain (NPCVM) and the striatum (NPCSTR) are intrinsically determined. A detailed analysis of the VM during development revealed Ngn2 and Mash1 expression in a DA progenitor domain. Interestingly, over-expression of either Ngn2 or Mashl induced neurogenesis from expanded NPCVM. Whereas Ngn2 inhibited cell division and the production of neurons even in the presence of mitogens, Mash1 allowed the progenitors to divide while retaining neurogenic potential. However, none of the new neurons derived by over-expressing Ngn2 or Mash1 were positive for DA neuronal markers such as tyrosine hydroxylase. Nurr 1 over-expression increased TH levels in a dose-dependant manner within both neurons and glia, suggesting a non-neuronalspecific activation of this enzyme by Nurr1. Double infection with Nurr1 and either Ngn2 or Mash1 resulted in the production of small numbers of TW neurons, which were larger in size when derived from NPCvm compared to NPCSTR. These data provide proof of concept that overexpression of multiple transcription factors can drive the fate of NPC first towards neurons, and then towards the DA phenotype. However, further factors may be required to generate fully ftinctional DA neurons. (c) 2006 Elsevier Inc. All rights reserved.