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The roles of bHLH factors Hes l/Hes3/Hes5 in the adult stem cell system

bHLH因子Hesl/Hes3/Hes5在成体干细胞系统中的作用

基本信息

批准号：
17209008
负责人：
KAGEYAMA Ryoichiro
金额：
$ 33.03万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17209008/
关键词：
Nestin-creERT2 mice floxed Hes1 mice stem cell tamoxifen-inducible conditional knock-out mice Hes1 oscillation adult brain bHLH factor ニューロン新生側脳室上衣下層海馬歯状回顆粒細胞下層 tamoxifen誘導性Cre 成体神経幹細胞 Hesl 消化管 cre-LoxP Hes コンディショナル・ノック

项目摘要

Neurogenesis usually does not occur in the adult brain, except for the following two regions: the subventricular zone of lateral ventricles and the subgranular zone of the dentate gyrus. The mechanism of maintenance of neural stem cells and the significance of neurogenesis in the adult brain remain to be analyzed. Here, we have produced Nestin-creERT2 mice, which express tamoxifen-inducible cre in neural stem cells, and floxed Hes1 mice, whose Hes1 gene can be deleted by cre. By using these mice, we specifically. deleted Hes genes in the adult brain and found that neurogenesis is blocked in these mutant mice. These results indicate that Hes genes regulate maintenance of neural stem cells in the adult brain as in the embryonic brain. We plan to examine the learning and memory ability of these mice to determine whether neurogenesis is required for such brain functions.We next found that Hes1 expression dynamically oscillates in the embryonic neural stem cells with a periodicity of about 2-3 hours and that this expression mode is important for proliferation and maintenance of these cells. We also found that Hes1 expression oscillates in the adult neural stem cells, and we plan to examine the significance of Hes1 oscillation in these cells.To reveal the roles of Hes1 in the adult gastrointestinal tract, we have produced cyp1A1-cre mice. By crossing these mice or villin-cre mice with floxed Hes1 mice, we specifically deleted Hes genes in the adult gastrointestinal tract. We found that in these mice, this organ becomes abnormal, and we plan to examine these defects in more detail.

成人大脑通常不发生神经发生，除了以下两个区域：侧脑室的室下区和齿状回的颗粒下区。神经干细胞在成体脑内的维持机制和神经发生的意义有待进一步分析。在这里，我们制作了nesting - creert2小鼠，在神经干细胞中表达他莫昔芬诱导的cre，以及floxed Hes1小鼠，其Hes1基因可以被cre删除。通过使用这些老鼠，我们特别。在成年小鼠大脑中删除了他的基因，发现这些突变小鼠的神经发生被阻断。这些结果表明，Hes基因在成人大脑中调控神经干细胞的维持，就像在胚胎大脑中一样。我们计划检查这些小鼠的学习和记忆能力，以确定这些脑功能是否需要神经发生。我们发现Hes1表达在胚胎神经干细胞中动态振荡，周期性约为2-3小时，这种表达模式对这些细胞的增殖和维持很重要。我们还发现Hes1在成体神经干细胞中表达振荡，我们计划检验Hes1振荡在这些细胞中的意义。为了揭示Hes1在成人胃肠道中的作用，我们制造了cyp1A1-cre小鼠。通过将这些小鼠或villin-cre小鼠与固定Hes1小鼠杂交，我们特异性地删除了成人胃肠道中的Hes基因。我们发现，在这些老鼠身上，这个器官变得异常，我们计划更详细地检查这些缺陷。