DRR1对小鼠神经干细胞分化以及神经元突起形成的影响

目的:本研究旨在阐明肾细胞癌下调蛋白1(DRR1)在小鼠大脑组织中的表达谱及相关生物学功能。方法:首先,通过real time RT-PCR的方法明确在不同发育阶段的小鼠大脑组织中DRR1的表达水平;利用免疫荧光染色法检测DRR1在原代培养的神经干细胞以及神经元中的表达情况。其次,采用real time RT-PCR的方法分别检测DRR1在诱导分化前后的神经干细胞中的表达水平。最后,利用慢病毒感染的方法在原代培养的神经干细胞以及神经元中分别上调或者下调DRR1的表达,进而评价DRR1对原代培养的神经干细胞的分化以及神经元的突起形成的影响。结果:DRR1在各个发育阶段的小鼠大脑组织中均有表达,并且其表达水平随发育呈逐渐上升趋势。DRR1在分化前后的神经干细胞中均表达,但在诱导分化后的细胞中的表达水平显著高于其分化前的表达水平(P<0.01)。同时,过表达DRR1可促进神经干细胞的分化。DRR1在分化成熟的原代神经元的树突以及轴突均有表达,且DRR1的表达水平影响神经元的突起形成(P<0.01)。结论:DRR1在各发育阶段的小鼠大脑及分化前后的神经干细胞中均有表达,其作用与神经干细胞分化调控以及神经元突起形成有关。

The effect of DRR1 on the differentiation of mouse neural stem cells and the neurites formation of mouse neurons

Objective:The aim of this study was to elucidate the expression profile and biological functions of downregulated renal cell carcinoma 1(DRR1)in mouse brain.Methods:First,the expression level of DRR1 in the mouse brain of different developmental stages was examined by real time RT-PCR.And immunofluorescence staining was used to detect the expression profile of DRR1 in primary cultured neural stem cells and neurons.Second,the expression of DRR1 in undifferentiated and differentiated neural stem cells was detected with real time RT-PCR.Finally,the differentiation ability of neural stem cells and neurite formation ability of neurons were evaluated after overexpression or downregulation of DRR1 through lentivirus infection.Results:DRR1 was broadly expressed in the mouse brain during all developmental stages,and the expression level of DRR1 increased gradually with development.DRR1 was expressed in both the undifferentiated neural stem cells and differentiated cells,and higher DRR1 expression level was found in the differentiated cells(P<0.01).Meanwhile,overexpression of DRR1 promoted the differentiation of neural stem cells.DRR1 was expressed in both dendrites and axons in primary cultured neurons.The down-regulation of DRR1 inhibited the neurits formation of neurons(P<0.01).Conclusion:DRR1 was expressed in the mouse brain of different developmental stages.The expression of DRR1 was detected in both undifferentiated and differentiated neural stem cells.DRR1 mediates the differentiation of neural stem cells and the neurites formation of neurons.