转录因子COUP-TFI和COUP-TFII调控大脑皮质中间神经元发生发育的分子机制

大脑皮质由兴奋性投射神经元和抑制性中间神经元组成，中间神经元对投射神经元活动的精细调控是大脑皮质发挥正常生理功能的基础。研究发现，中间神经元的发生发育异常与神经系统疾病密切相关，如癫痫、自闭症和精神分裂症等。大脑皮质中间神经元的多样性起源于胚胎发育时期各种转录因子对神经干细胞精密和复杂的调控。转录因子Coup TFI/II属于孤核受体家族成员，在神经系统发育中调控神经发生、神经干细胞分化和迁移以及轴突生长，但它们在大脑皮质中间神经元发生发育过程中的调控及可能分子机制却不甚清楚。本课题将利用条件性基因敲除技术，结合免疫组织化学、细胞和分子生物学以及电生理等方法，使用激光共聚焦和活细胞成像手段，研究转录因子Coup-TFI和Coup-TFII对大脑皮质中间神经元发生发育的调控作用及分子机制。这一研究将为利用神经干细胞治疗神经系统疾病提供实验依据。

The mammalian neocortex contains two main neuron subpopulations, the excitatory glutamatergic projection neurons and the inhibitory GABAergic interneurons. It is being recognized that cortical interneurons through their maintenance of the excitatory/inhibitory balance in the cerebrum are central to the normal function of the nervous system. Moreover, recent studies in mouse models and humans have indicated that interneuron dysfunction is associated with neurological and psychiatric diseases such as epilepsy, schizophrenia and autism。The diversity of cortical interneurons derived from concise and complex regulation by transcription factors during embryonic development. 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 regulation of neural development. However, the regulation and molecular mechanism underlying Coup-TFI and Coup-TF II in the regulation of cortical interneurons development remains totally unknown. In the present project, the regulation of Coup-TFI and Coup-TFII in cortical interneuron development and underlying molecular mechanisms will be investigated by means of immunostaining, cellular and molecular biology methods, confocal scanning, patch clamp and Time-lapse video recording. It will provide experimental data for employing stem cells derived from human to ameliorate neurological disorders associated with cortical interneuron dysfunction.