靶向stat3基因干扰对小鼠神经干细胞增殖分化影响的实验研究

发布时间：2018-04-26 23:13

本文选题：神经上皮 + 神经干细胞　；参考：《第三军医大学》2006年硕士论文

【摘要】：神经系统是机体最重要和最复杂的系统，起源于神经管(neural tube)和神经嵴，神经管形成中枢神经系统(central nervous system，CNS)(脑和脊髓)，神经嵴形成周围神经系统的神经节等。CNS正常发生的关键是神经板内外相关组织细胞行为的准确进行和协同，神经管的形成是该过程结束的标志。神经管发生是一个重要的涉及到建立中枢神经系统原基的胚胎学事件，是指从神经板出现到神经管关闭的发育过程。神经管管壁最初是由一层较厚的假复层上皮组成，称为神经上皮(neuroepithenium)。神经上皮不断增殖的同时细胞也逐渐开始进行迁移和分化，逐渐形成三层结构的管壁，由内向外依次为室管膜层，套层和边缘层。在此过程中，神经上皮细胞处于活跃的细胞增殖周期中，为具有多种分化潜能的神经干细胞，伴随着分化演变。神经上皮中神经干细胞的增殖迁移以及分化是神经系统发育的关键环节。研究发现神经管形成时期极易受多种内外因素的干扰而致畸，神经管缺陷(neural tube defect，NTD)就是其中发病率最高的一种，表现为各种脑和脊髓的发育畸形。多年来的研究提示NTD的发生与神经上皮的异常发育密切相关。从基因水平而言，，神经上皮的发育过程是一系列基因按照高度特异的时空模式表达并相互作用的结果，但迄今对此复杂过程的基因表达与调控的了解还很少。信号转导与转录激活因子3(signal transducer and activator of transcription 3，STAT3)是STAT家族的成员之一，作为重要的信号转导因子，参与多种基因的表达和调控，并与其他转录因子一起形成复杂的调控网络，已证实参与到胚胎的神经系统、眼发育等过程中。神经管闭合后，神经管上皮细胞进一步增生、分化和迁移，其前段呈现三个膨大，依次称为前脑泡、中脑泡和菱脑泡。神经管上皮细胞的增生、分化和迁移对于神经系统正常结构和功能的建立十分重要。纪华等通过原位杂交等技术检测STAT3mRNA在E9.5-E11.5的小鼠胚胎中的表达情况，结果依次显示为起始的前脑泡剧增、转移至中脑泡、最后仅存于菱脑泡中的狭窄区域。提示STAT3可能参与了神经管头段的区域化，即前脑、中脑、菱脑三个脑泡的形成。已有研究发现，STAT3蛋白在植入后胚胎中即开始有所表达，尤其是在E10.5至
[Abstract]:The nervous system is the most important and complex system of the body, originating from neural tubes and neural crest. The key to the normal occurrence of CNS in the central nervous system, such as the brain and spinal cord, the formation of peripheral nervous system ganglion, etc., is the accurate and synergistic behavior of the related histocytes inside and outside the nerve plate. The formation of a neural tube marks the end of the process. Neurotubulogenesis is an important embryological event involved in the establishment of the primordium of the central nervous system (CNS) and refers to the developmental process from the appearance of the nerve plate to the closure of the neural tube. The neural tube wall was originally composed of a thicker pseudostratified epithelium called neuroepithelial epithelium. At the same time the neural epithelium proliferated and the cells began to migrate and differentiate gradually forming a three-layer structure of the wall from the inside to the outside of the ependymal layer sleeve layer and marginal layer. In this process, neuroepithelial cells are active in the cell proliferation cycle, neural stem cells with multiple differentiation potential, with the evolution of differentiation. The proliferation, migration and differentiation of neural stem cells in neural epithelium are the key to the development of nervous system. It has been found that neural tube formation is easily affected by many internal and external factors, and neural tube defectNTD is one of the most common deformity of brain and spinal cord. Years of studies have shown that the occurrence of NTD is closely related to abnormal development of neuroepithelium. At the gene level, the developmental process of neuroepithelium is the result of a series of genes expressed and interacted according to a highly specific spatiotemporal pattern, but so far little has been known about the gene expression and regulation of this complex process. As an important signal transduction factor, signal transduction and transcriptional activator (3(signal transducer and activator of transcription _ 3 / STAT _ 3) is a member of the STAT family. As an important signal transduction factor, it participates in the expression and regulation of many genes and forms a complex regulatory network with other transcription factors. It has been proved to be involved in the embryonic nervous system, eye development, etc. After the closure of the neural tube, the epithelial cells of the neural tube were further proliferated, differentiated and migrated. The anterior segment of the neural tube showed three enlargement, which were called forebrain vesicles, mesencephalic vesicles and rhomboid vesicles in turn. The proliferation, differentiation and migration of neural tube epithelial cells are very important for the establishment of normal structure and function of nervous system. Ji Hua et al detected the expression of STAT3mRNA in mouse embryos of E9.5-E11.5 by in situ hybridization. The results showed that the initial forebrain vesicles increased sharply and metastasized to the mesencephalic vesicles, and finally only in the narrow areas of the rhomboid vesicles. The results suggest that STAT3 may be involved in the formation of three brain vesicles in the forebrain, midbrain and rhomboid. It has been found that STAT3 protein begins to express in post-implantation embryos, especially in E10.5 to E10.5.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R346

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