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EFFECTS OF INTRACELLULAR AND EXTRACELLULAR FACTORS ON THE TERMINAL CELL DIVISION OF NEURAL STEM CELLS

细胞内外因子对神经干细胞终末细胞分裂的影响

基本信息

批准号：
12490032
负责人：
MARUNOUCHI Tohru
金额：
$ 3.07万
依托单位：
Fujita Health University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12490032/
关键词：
Neural Stem cells Terminal Cell Division Transcription Regulatory Factors Notch NZF Electro Poration GFP Confocal Microscope 転写調整因子エレクトロポレーション

项目摘要

In the terminal cell division in the developmental systems, inhibitors of cell cycle progression, such as P21 and transcription factors of differentiation such as bHLH are closely related. We investigated the relationship between Notch and a member of bHLH factors, Mash 1 in Notch2-targeted mice, and found that Notch2 suppressed the expression of Mash1 in the roof plate of E10-11 embryos and that deletion of Notch2 activated the expression of Mash1 gene and inhibited cell cycle progression. It was also shown that Notch2 introduced into P19 inhibited the differentiation into neural cells and adjacent cells were differentiated to neural cells, suggesting the possibility to analyze the lateral inhibitory system using culture cells.We have shown that Notch and DSL family genes are expressed radial glia in cerebellum and dentategyrus of hippocampus, suggesting that expression of Notch is positively related to proliferation of glia and negatively to its differentiation. In the slice culture of newborn rat cerebellum, plelotrophin-PTP-ζ signaling is necessary for normal morphogenesis of Purkinje cell dendrites.We cloned three Zn finger type transcription regulatory factors, NZF1, 2, 3 from mouse cDNA library. Their expression was activated in developing central nervous system during E9.5〜15. NZF is expressed in newly generated neurons (NZF2b) or in neuronal cells, which have just ceased proliferation (NZF3).By introduction of neuronal bHLH genes, mouse ES cells were induced to differentials into neural cells.

在发育系统的终末细胞分裂中，细胞周期进程抑制剂（例如P21）和分化转录因子（例如bHLH）密切相关。我们在Notch 2靶向小鼠中研究了Notch与bHLH因子成员Mash 1之间的关系，发现Notch 2抑制了E10-11胚胎顶板中Mash 1的表达，Notch 2的缺失激活了Mash 1基因的表达并抑制了细胞周期进程。另外，还显示了导入P19的Notch 2抑制了向神经细胞的分化，并且邻近细胞分化为神经细胞，这表明了使用培养细胞分析侧抑制系统的可能性。我们已经显示了Notch和DSL家族基因在小脑和海马齿状回的放射状胶质细胞中表达，提示Notch的表达与胶质细胞的增殖呈正相关，与胶质细胞的分化呈负相关。在培养的新生大鼠小脑切片中，Plelotrophin-PTP-β信号通路是浦肯野细胞树突正常形态发生所必需的。E9.5 ~ 15在发育中的中枢神经系统中表达被激活。NZF表达于新生神经元（NZF 2b）或停止增殖的神经元（NZF 3）。