Ectopic expression of nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation accompanying with abnormal apoptosis in the developing mouse telencephalon.
Ectopic expression of nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation accompanying with abnormal apoptosis in the developing mouse telencephalon.
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DOI：
10.1371/journal.pone.0074975
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu FC
中科院分区：
文献类型：
--
作者：
Chang SL;Chen SY;Huang HH;Ko HA;Liu PT;Liu YC;Chen PH;Liu FC
Nolz-1 是 NET 锌指蛋白家族的小鼠成员，在发育过程中纹状体有丝分裂后分化神经元中表达。为了探讨Nolz-1在调节前脑神经发生中的功能，我们研究了Nolz-1在神经祖细胞中异位表达的影响。我们生成了 Cre-loxP 依赖性条件转基因小鼠，其中 Nolz-1 在增殖性神经祖细胞中异位表达。通过将Nolz-1条件转基因小鼠与nestin-Cre小鼠杂交，在神经祖细胞中异位表达Nolz-1，导致双转基因小鼠端脑发育不全。端脑中发现神经祖细胞增殖减少，端脑 E11.5-12.5 生发区中 BrdU−、Ki67− 和磷酸组蛋白 3 阳性细胞的减少证明了这一点。转基因Nolz-1还促进细胞周期退出，因此可能促进祖细胞的过早分化，因为在心室区异位发现TuJ1阳性神经元，并且端脑中TuJ1免疫反应性普遍增加。此外，E12.5 生发区中存在强表达 TuJ1 的神经元簇。然而，其中一些强 TuJ1 阳性簇含有凋亡浓缩 DNA，表明不适当的过早分化可能导致某些祖细胞异常凋亡。与体内转基因小鼠分析一致，在体外三种不同的N18、ST14A和N2A神经细胞系中也观察到Nozl-1过表达在诱导细胞凋亡、抑制细胞增殖和促进神经元分化方面的类似作用。综上所述，我们的研究表明，神经祖细胞中 Nolz-1 的异位表达促进细胞周期退出/神经元过早分化，并诱导发育中的端脑异常凋亡。
Nolz-1, as a murine member of the NET zinc-finger protein family, is expressed in post-mitotic differentiating neurons of striatum during development. To explore the function of Nolz-1 in regulating the neurogenesis of forebrain, we studied the effects of ectopic expression of Nolz-1 in neural progenitors. We generated the Cre-loxP dependent conditional transgenic mice in which Nolz-1 was ectopically expressed in proliferative neural progenitors. Ectopic expression of Nolz-1 in neural progenitors by intercrossing the Nolz-1 conditional transgenic mice with the nestin-Cre mice resulted in hypoplasia of telencephalon in double transgenic mice. Decreased proliferation of neural progenitor cells were found in the telencephalon, as evidenced by the reduction of BrdU−, Ki67− and phospho-histone 3-positive cells in E11.5–12.5 germinal zone of telencephalon. Transgenic Nolz-1 also promoted cell cycle exit and as a consequence might facilitate premature differentiation of progenitors, because TuJ1-positive neurons were ectopically found in the ventricular zone and there was a general increase of TuJ1 immunoreactivity in the telencephalon. Moreover, clusters of strong TuJ1-expressing neurons were present in E12.5 germinal zone. Some of these strong TuJ1-positive clusters, however, contained apoptotic condensed DNA, suggesting that inappropriate premature differentiation may lead to abnormal apoptosis in some progenitor cells. Consistent with the transgenic mouse analysis in vivo, similar effects of Nozl-1 over-expression in induction of apoptosis, inhibition of cell proliferation and promotion of neuronal differentiation were also observed in three different N18, ST14A and N2A neural cell lines in vitro. Taken together, our study indicates that ectopic expression of Nolz-1 in neural progenitors promotes cell cycle exit/premature neuronal differentiation and induces abnormal apoptosis in the developing telencephalon.
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DOI：
10.1242/dev.028043
发表时间：
2009-01
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Ji SJ;Periz G;Sockanathan S
通讯作者：
Sockanathan S
影响因子：
2.5
作者：
Hoyle, J;Tang, YP;Sive, H
通讯作者：
Sive, H
影响因子：
3.7
作者：
Wu CS;Yen CJ;Chou RH;Li ST;Huang WC;Ren CT;Wu CY;Yu YL
通讯作者：
Yu YL
影响因子：
3.7
作者：
Boix, J;Fibla, J;Comella, JX
通讯作者：
Comella, JX
影响因子：
2.5
作者：
Ko, Hsin-An;Chen, Shih-Yun;Liu, Fu-Chin
通讯作者：
Liu, Fu-Chin