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

神经发生通常不发生在成人的大脑中，除了以下两个区域：侧脑室的脑室下区和齿状回的颗粒下区。神经干细胞的维持机制和成人脑中神经发生的意义仍有待分析。在这里，我们产生了在神经干细胞中表达他莫昔芬诱导的Cre的Nestin-creERT2小鼠，以及可以通过Cre缺失其Hes1基因的Hes1小鼠。通过使用这些老鼠，我们特别地。删除了成年大脑中的Hes基因，并发现这些突变小鼠的神经发生受阻。这些结果表明，HES基因调节着神经干细胞在成人大脑中的维持，就像在胚胎大脑中一样。我们计划检测这些小鼠的学习和记忆能力，以确定这些大脑功能是否需要神经发生。接下来，我们发现Hes1在胚胎神经干细胞中的表达以大约2-3小时的周期动态振荡，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在成年神经干细胞中的表达振荡，我们计划检测这些细胞中Hes1振荡的意义。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Hes1小鼠杂交，我们特意删除了成人胃肠道中的Hes基因。我们发现，在这些小鼠中，这个器官变得异常，我们计划更详细地检查这些缺陷。

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.