Id2在成年大鼠脑中的表达及其影响SVZa神经干细胞发育分化的初步研究
本文关键词:Id2在成年大鼠脑中的表达及其影响SVZa神经干细胞发育分化的初步研究 出处:《第三军医大学》2005年硕士论文 论文类型:学位论文
更多相关文章: Id2 大鼠 脑 SVZa 神经干细胞 RMS 发育 分化
【摘要】:随着对神经干细胞较为深入的研究,位于侧脑室附近的室管膜前下区(Anterior subvcntricular zone,SVZa)和海马被公认为成年哺乳动物神经系统中神经干细胞最为集中的部位。研究发现,SVZa区神经干细胞产生后,沿喙侧迁移流(Rostral migratory stream,RMS)朝嗅脑方向迁移,成为出生后嗅脑(球)(Olfactory bulb,OB)神经元终身更新的来源。SVZa区神经干细胞除具有一般神经干细胞特征外,还有其自身特点,即在向OB迁移的过程中(RMS区)始终保持不分化状态,在到达嗅脑后再分化为成熟神经细胞和神经胶质细胞。 神经干细胞分化是外源性信号与内源性信号共同作用的结果,外源性信号如有丝分裂因子EGF、T_3、维甲酸、糖皮质激素、血清等,内源性信号如T_3核受体等都对神经干细胞分化具有调控作用。我们研究组在以前的研究中发现细胞因子BMPs、Mashl、Pax6、Wnt等对SVZa区神经干细胞的增殖、迁移、分化具有一定调控作用,这些因子在RMS区表达均很弱,且都有促进神经干细胞分化的作用。但SVZa区神经干细胞在向OB迁移的RMS区始终保持不分化状态的调控机制是什么呢?目前的研究还不清楚。神经干细胞分化是正、负双向调控因子共同作用的结果,我们课题组已经研究了部分正向调控因子的作用,但抑制SVZa区神经干细胞在迁移过程中分化的机制是什么呢?由于Id2具有其负向调控因子的特点(见后),因此我们选择了Id2作为研究对象,期望为进一步阐明SVZa区神经干细胞在迁移过程中保持不分化的调控机制积累更丰富的资料。 含HLH结构域的蛋白可分为两类:碱性螺旋-环-螺旋(basic helix-loop-helix,bHLH)和Id(inhibitor of DNA binding)。bHLH可分为A型和B型。A型bHLH为一种遍在蛋白,它既可以与正调控蛋白聚合,又可以与负调控蛋白聚合;B型bHLH蛋白为正调控蛋白。Id则为负调控蛋白,是bHLH因子的抑制因子,其家族有Id1、Id2、Id3、Id4共4个成员。与bHLH蛋白不同,Id蛋白缺乏结合DNA的碱性区域。B型bHLH蛋白能与A型bHLH蛋白形成同源或异源二聚体,此二聚体再与E-box蛋白结合来实现其对下游基因的转录。Id与A型bHLH蛋白结合形成二聚体,从而干扰B型bHLH蛋白与A型bHLH蛋白结合形成同源或异源二聚体。最初的研究发现,Id蛋白一般在
[Abstract]:With the further study of neural stem cells, the anterior and inferior ependymal subvcntricular zone is located near the lateral ventricle. SVZA) and hippocampus are recognized as the most concentrated sites of neural stem cells in adult mammalian nervous system. Rostral migratory streamer moved towards olfactory brain and became olfactory bulb after birth. The source of lifelong renewal of OB neurons. SVZa neural stem cells have their own characteristics in addition to the general characteristics of neural stem cells. In the process of migration to OB, the RMS region remained undifferentiated, and was then redifferentiated into mature nerve cells and glial cells after reaching the olfactory brain. Neural stem cell differentiation is the result of both exogenous and endogenous signals. Exogenous signals such as EGFT _ 3, retinoic acid, glucocorticoid, serum, and so on. Endogenous signals, such as T _ S _ 3 nuclear receptors, regulate the differentiation of neural stem cells. Our team found the cytokine BMPsMashln Pax6 in previous studies. Wnt and so on have certain regulation on the proliferation, migration and differentiation of neural stem cells in SVZa region, and these factors are very weak in the RMS region. But what is the regulatory mechanism of the neural stem cells in the SVZa region to remain undifferentiated in the RMS region that migrate to OB? The differentiation of neural stem cells is the result of both positive and negative bidirectional regulatory factors. Our team has studied the role of some positive regulatory factors. But what is the mechanism that inhibits the differentiation of neural stem cells in the SVZa region during migration? Because Id2 has the characteristics of negative regulatory factors (see back), we chose Id2 as our research object. It is expected to further clarify the regulatory mechanism of neural stem cells (NSCs) in the SVZa region to maintain undifferentiation during migration. Proteins containing HLH domain can be classified into two categories: basic helix-loop-helix. BHLH) and Id(inhibitor of DNA binding).bHLH can be divided into A type and B type. A type bHLH is a kind of protein. It can be polymerized with both positive and negative regulatory proteins. Type B bHLH protein is a positive regulatory protein. ID is a negative regulatory protein. It is an inhibitory factor of bHLH factor, and its family has Id1, Id2, Id3. There are 4 members of Id4. Unlike bHLH protein, the basic region. B type bHLH protein, which lacks binding to DNA, can form homologous or heterodimer with type A bHLH protein. The dimer then binds to E-box protein to achieve the transcription of downstream gene. ID binds to type A bHLH protein to form a dimer. It interferes with the binding of type B bHLH protein to type A bHLH protein to form homologous or heterodimer.
【学位授予单位】:第三军医大学
【学位级别】:硕士
【学位授予年份】:2005
【分类号】:R329
【共引文献】
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