靶向stat3基因干擾對(duì)小鼠神經(jīng)干細(xì)胞增殖分化影響的實(shí)驗(yàn)研究
發(fā)布時(shí)間:2018-04-26 23:13
本文選題:神經(jīng)上皮 + 神經(jīng)干細(xì)胞 ; 參考:《第三軍醫(yī)大學(xué)》2006年碩士論文
【摘要】:神經(jīng)系統(tǒng)是機(jī)體最重要和最復(fù)雜的系統(tǒng),起源于神經(jīng)管(neural tube)和神經(jīng)嵴,神經(jīng)管形成中樞神經(jīng)系統(tǒng)(central nervous system,CNS)(腦和脊髓),神經(jīng)嵴形成周圍神經(jīng)系統(tǒng)的神經(jīng)節(jié)等。CNS正常發(fā)生的關(guān)鍵是神經(jīng)板內(nèi)外相關(guān)組織細(xì)胞行為的準(zhǔn)確進(jìn)行和協(xié)同,神經(jīng)管的形成是該過程結(jié)束的標(biāo)志。神經(jīng)管發(fā)生是一個(gè)重要的涉及到建立中樞神經(jīng)系統(tǒng)原基的胚胎學(xué)事件,是指從神經(jīng)板出現(xiàn)到神經(jīng)管關(guān)閉的發(fā)育過程。神經(jīng)管管壁最初是由一層較厚的假復(fù)層上皮組成,稱為神經(jīng)上皮(neuroepithenium)。神經(jīng)上皮不斷增殖的同時(shí)細(xì)胞也逐漸開始進(jìn)行遷移和分化,逐漸形成三層結(jié)構(gòu)的管壁,由內(nèi)向外依次為室管膜層,套層和邊緣層。在此過程中,神經(jīng)上皮細(xì)胞處于活躍的細(xì)胞增殖周期中,為具有多種分化潛能的神經(jīng)干細(xì)胞,伴隨著分化演變。神經(jīng)上皮中神經(jīng)干細(xì)胞的增殖遷移以及分化是神經(jīng)系統(tǒng)發(fā)育的關(guān)鍵環(huán)節(jié)。研究發(fā)現(xiàn)神經(jīng)管形成時(shí)期極易受多種內(nèi)外因素的干擾而致畸,神經(jīng)管缺陷(neural tube defect,NTD)就是其中發(fā)病率最高的一種,表現(xiàn)為各種腦和脊髓的發(fā)育畸形。多年來的研究提示NTD的發(fā)生與神經(jīng)上皮的異常發(fā)育密切相關(guān)。從基因水平而言,,神經(jīng)上皮的發(fā)育過程是一系列基因按照高度特異的時(shí)空模式表達(dá)并相互作用的結(jié)果,但迄今對(duì)此復(fù)雜過程的基因表達(dá)與調(diào)控的了解還很少。 信號(hào)轉(zhuǎn)導(dǎo)與轉(zhuǎn)錄激活因子3(signal transducer and activator of transcription 3,STAT3)是STAT家族的成員之一,作為重要的信號(hào)轉(zhuǎn)導(dǎo)因子,參與多種基因的表達(dá)和調(diào)控,并與其他轉(zhuǎn)錄因子一起形成復(fù)雜的調(diào)控網(wǎng)絡(luò),已證實(shí)參與到胚胎的神經(jīng)系統(tǒng)、眼發(fā)育等過程中。神經(jīng)管閉合后,神經(jīng)管上皮細(xì)胞進(jìn)一步增生、分化和遷移,其前段呈現(xiàn)三個(gè)膨大,依次稱為前腦泡、中腦泡和菱腦泡。神經(jīng)管上皮細(xì)胞的增生、分化和遷移對(duì)于神經(jīng)系統(tǒng)正常結(jié)構(gòu)和功能的建立十分重要。紀(jì)華等通過原位雜交等技術(shù)檢測STAT3mRNA在E9.5-E11.5的小鼠胚胎中的表達(dá)情況,結(jié)果依次顯示為起始的前腦泡劇增、轉(zhuǎn)移至中腦泡、最后僅存于菱腦泡中的狹窄區(qū)域。提示STAT3可能參與了神經(jīng)管頭段的區(qū)域化,即前腦、中腦、菱腦三個(gè)腦泡的形成。 已有研究發(fā)現(xiàn),STAT3蛋白在植入后胚胎中即開始有所表達(dá),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.
【學(xué)位授予單位】:第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2006
【分類號(hào)】:R346
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 紀(jì)華,李澤桂,馬路,丁震宇,蔡文琴,傅新元,常智杰,劉力;STAT3在小鼠胚胎神經(jīng)系統(tǒng)發(fā)育中的表達(dá)[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2005年07期
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