Regulation of neurogenesis by two-hour cycle biological clock

在胚胎神经干细胞中，Hes1的表达振荡周期约为2小时，Hes1的振荡驱动前膜基因Ngn2和Notch配体Dll1的振荡表达。Dll1振荡导致Notch信号的相互激活和神经干细胞的维持。Hes1表达消失后，Ngn2持续表达，促进神经元分化。在成人大脑中，神经干细胞的神经发生是必不可少的，神经干细胞由Notch-Hes通路维持。这些结果揭示了节律性基因Hes1在胚胎和成体神经干细胞调控中的重要意义。

In embryonic neural stem cells, Hes1 expression oscillates with a period of about two hours, and Hes1 oscillations drive oscillatory expression of the proneural gene Ngn2 and the Notch ligand Dll1. Dll1 oscillations lead to mutual activation of Notch signaling and maintenance of neural stem cells. When Hes1 expression disappears, Ngn2 is expressed in a sustained manner, thereby promoting neuronal differentiation. In the adult brain, neurogenesis from neural stem cells is essential, and neural stem cells are maintained by the Notch-Hes pathway. These results revealed the significance of the rhythmic gene Hes1 in regulation of embryonic and adult neural stem cells.