脑室下层和海马颗粒细胞层下层是成年哺乳动物脑内神经发生的两个部位，神经干细胞所产生新生神经元迁移的距离和目的地及成熟和分化的过程存在共性和差异，它们整合到已有神经环路并发挥功能方面既有共性也有区别。转录因子Coup TFI/II属于孤核受体家族成员，调控哺乳动物代谢、肿瘤和癌症形成及胃和肌肉等系统发育。Coup TFI/II在中枢神经系统的发生发育中发挥重要作用，调控大脑皮质区域化、神经元轴突发育、前脑发育以及大脑皮质中间神经元分化。但Coup TFI/II在哺乳动物成年脑内神经发生中的作用、分子机制及神经环路的形成却没有深入的研究。本课题利用条件性基因敲除技术，结合形态学、分子生物学、电生理学、单细胞克隆分析及单细胞RNA-Seq等技术，探讨Coup TFI/II调控脑室下层和海马神经发生的分子机制。这一研究将为利用和改变脑内不同区域的自体神经干细胞治疗神经系统疾病提供依据。

Neural stem cells persist in the subventricular zone (SVZ) and the subgranular zone (SGZ) within the dentate gyrus in the adult brain. Neurogenesis in the SVZ and SGZ exhibit similarities and differences: the migration distance, the destination, the maturation, differentiation and the integration into the local circuits. The transcription factor Coup TF I and Coup TFII are nuclear receptors belonging to the superfamily of the steroid/thyroid hormone receptors, and have been involved in various key events during embryonic development and organogenesis. They play critical function during development and maturation of the central nervous system, such as area pattering, axon maturation, forbrain development and differentiation of cortical interneuron. However, the function and underlying molecular mechanism that Coup TF I/II regulate adult neurogenesis remain unclear. In this project, by using conditional gene mutation technology combining with morphology, cell and molecular biology methods, electrical physiology, single cell clonal analysis and single cell RNA-Seq methods, we will investigate the regulation of Coup TFI and Coup TFII in individual niche components at distinct stages of adult neurogenesis. It will provide experimental data for employing stem cells derived from human to ameliorate neurological disorders.