转录因子Tbx2在神经嵴干细胞衍生的黑色素细胞增殖与分化中的功能研究

The study of development and differentiation of neural crest stem cell has an important biological and medical significance. Melanocyte derives from neural crest stem cell and transcription factor Mitf palys a crucial role in its proliferation and differentiation. Transcription factor Tbx2 is regulated by Mitf in melanocyte, however the role of Tbx2 in melanocyte development is largely unknown. By utilizing mice as model and neural crest stem cell-derived melanocyte as primary experimental system, the project will examine the spaciotemporal expression of Tbx2 during melanocyte development by wholemount ISH and immunostaining and investigate the functional role of Tbx2 in melanocyte proliferation and differentiation through RNAi and gene overexpression.This project will reveal the functional role of Tbx2 in the development and differentiation of melanocyte, provide insight into the molecular regulation network underlying stem cell directional differentiation and provide a clue for the treatment of diseases arising from the aberrant melanocyte proliferation and differentiation.

神经嵴干细胞的发育分化研究具有重要的生物学和医学意义。黑色素细胞是神经嵴干细胞衍生系之一，转录因子Mitf在其增殖与分化中起着极其重要的作用。转录因子Tbx2在黑色素细胞中的表达受到Mitf调控，但Tbx2在黑色素细胞发育中的功能目前仍不清楚。本课题拟采用小鼠作为动物模型和神经嵴干细胞衍生的黑色素细胞作为首选实验系统，通过整胚原位杂交和免疫荧光技术分析Tbx2在黑色素细胞发育中的时空表达；运用RNA干扰和基因过表达探讨Tbx2在黑色素细胞增殖与分化中的功能。本研究将揭示Tbx2在黑色素细胞发育分化中的功能，促进对干细胞定向分化分子调控的认识，并为寻找治疗黑色素细胞增殖与分化异常与疾病的方法提供理论依据和新思路。

神经嵴干细胞的发育研究具有重要的生物学和医学意义。黑色素细胞是神经嵴干细胞衍生系之一，转录因子Tbx2是黑色素细胞发育关键调控因子MITF在黑色素细胞中的靶基因，但Tbx2在黑色素细胞增殖与分化中的功能目前仍不清楚。为了解析Tbx2在黑色素细胞发育中的功能，我们首先分析了Tbx2的时空表达；继而在黑色素细胞系melan-a和神经嵴细胞诱导的原代黑色素细胞中，利用RNA干扰分析了Tbx2在黑色素细胞增殖中的功能及其分子机理。我们发现，Tbx2在神经嵴干细胞诱导的黑色素细胞和出生后三天的小鼠皮肤毛囊表达；Tbx2通过直接调控细胞周期蛋白Cyclin D1的表达来调节黑色素细胞的增殖。这一原创性研究为加深理解Tbx2调节黑色素细胞增殖分化的分子和细胞机制，进而阐明MITF在黑色素细胞发育与致病过程中的调控机理起到了重要的作用。