Nestin promoter/enhancer directs transgene expression to precursors of adult generated periglomerular neurons
Nestin promoter/enhancer directs transgene expression to precursors of adult generated periglomerular neurons
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DOI：
10.1002/cne.20179
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发表时间：
2004-07-12
影响因子：
2.5
通讯作者：
Picciotto, MR
中科院分区：
文献类型：
--
作者：
Beech, RD;Cleary, MA;Picciotto, MR
脑室下区(SVZ)是成人大脑中一个主要的神经源性区域。来自SVZ的细胞可分化出两类嗅球中间神经元：颗粒细胞和球周细胞。目前，人们对引导这些新生成的神经元变成颗粒状或PGT神经元的信号通路知之甚少。在本研究中，我们使用巢蛋白启动子和增强子来指导四环素反式激活因子(TTA)的表达。我们获得了两个独立的Nestin-TTA转基因动物品系，并将这两个品系的创始小鼠与含有四环素调控转基因(MCREB)的小鼠杂交，mCREB的表达可作为Nestin-TTA转基因活性的标志。在两种细胞系中，mCREB表达均见于SVZ和吻端游走流中的增殖细胞亚群。令人惊讶的是，在Nestin-TTA小鼠的两个品系中，转基因在嗅球中的表达仅限于PG神经元，而在颗粒细胞中缺失，这表明这个Nestin启动子结构区分了两者。这两个神经元之间的群体。转基因表达存在于PG神经元的几个亚型中，包括表达Calretinin、Calbindin、GAD67和酪氨酸羟基酶的神经元。这些结果表明，产生PG的是SVZ前体细胞的一个独特亚群，而不是颗粒细胞。在这一亚群神经元前体中表达不同转基因的能力提供了一个强大的系统来定义调节嗅球中成年产生的神经元的分化和存活的信号。(C)2004年Wiley-Liss公司
The subventricular zone (SVZ) is a major neurogenic region in the adult brain. Cells from the SVZ give rise to two populations of olfactory bulb interneurons: the granule cells and periglomerular (PG) cells. Currently, little is known about the signaling pathways that direct these newly generated neurons to become either granule or PGT neurons. In the present study, we used the nestin promoter and enhancer to direct expression of the tetracycline transactivator (tTA). We generated two independent strains of nestin-tTA transgenic animals and crossed founder mice from both lines to mice containing a tetracycline-regulated transgene (mCREB) whose expression served as a marker for the activity of the nestin-tTA transgene. mCREB expression occurred in a subset of proliferating cells in the SVZ and rostral migratory stream in both lines. Surprisingly, in both lines of nestin-tTA mice transgene expression in the olfactory bulb was limited to PG neurons and was absent from granule cells, suggesting that this nestin promoter construct differentiates between. the two interneuronal populations. Transgene expression occurred in several subtypes of PG neurons, including those expressing calretinin, calbindin, GAD67, and tyrosine hydroxylase. These results suggest that a unique subset of SVZ precursor cells gives rise to PG, and not granule cells. The ability to express different transgenes within this subpopulation of neuronal precursors provides a powerful system to define the signals regulating the differentiation and survival of adult-generated neurons in the olfactory bulb. (C) 2004 Wiley-Liss, Inc.