BMP-4在视网膜与视神经中的分布及对少突胶质前体细胞分化的影响

发布时间：2018-04-13 13:40

  本文选题：BMP-4 + 少突胶质前体细胞　； 参考：《复旦大学》2010年硕士论文

【摘要】： 在视觉系统发育过程中,来源于脑的少突胶质前体细胞汇集于视交叉处,并继续沿着视神经向视网膜方向迁移。这些细胞在胚胎后期至生后早期分化为少突胶质细胞,并包裹节细胞轴突形成有髓神经纤维。然而,大多数哺乳动物的视神经纤维进入筛板后,其髓鞘即消失。究其原因,一般认为可能与筛板处存在抑制少突胶质前体细胞迁移的特殊屏障有关,但具体机制仍有待深入研究。 目的通过研究BMP-4在视神经及视网膜中的表达情况,并通过体外实验研究BMP-4对少突胶质前体细胞分化的影响,及BMP-4与Olig2的相互关系,为视网膜及视神经乳头不形成髓鞘的机制提供实验依据,为相关髓鞘疾病的治疗提供新的思路。 方法用免疫组织化学染色检测BMP-4在视网膜及视神经乳头中的表达及分布情况。采用恒温振荡法和差速贴壁法分离纯化少突胶质前体细胞,并研究BMP-4对少突胶质前体细胞分化发育的影响。用Western Blot研究BMP-4与Olig2的相互关系。 结果在发育阶段中,BMP-4仅选择性表达在视神经乳头处。成功纯化少突胶质前体细胞,当将培养液中的促细胞增殖因子撤除后,少突胶质前体细胞自发向少突胶质细胞分化和成熟,而加入BMP-4后,少突胶质前体细胞的分化方向发生变化,高浓度的BMP-4使少突胶质前体细胞最终分化为Ⅱ型星形胶质细胞。随着BMP-4浓度的增高,蛋白Olig2的表达量也逐渐降低。 结论在视神经乳头处高浓度表达的BMP-4蛋白有可能作用于迁移至筛板处的少突胶质前体细胞。BMP-4在体外可抑制少突胶质前体细胞向少突胶质细胞的分化,并促使其向星形胶质细胞分化。通过激活少突胶质前体细胞内的相关信号途径,下调少突胶质前体细胞内Olig2蛋白的表达水平,从而抑制少突胶质前体细胞向少突胶质细胞方向分化,并促进其向星形胶质细胞方向分化。
[Abstract]:During the development of the visual system, oligodendrocyte precursor cells from the brain converge at the optic chiasma and continue to migrate along the optic nerve to the retina.These cells differentiate into oligodendrocytes from late embryo to early postnatal stage and form myelinated nerve fibers by wrapping axons of ganglion cells.However, when the optic nerve fibers of most mammals enter the sieve plate, their myelin sheath disappears.It is generally believed that there is a special barrier at the sieve plate to inhibit the migration of oligodendrocyte precursor cells, but the specific mechanism remains to be further studied.Objective to study the expression of BMP-4 in optic nerve and retina, and to investigate the effect of BMP-4 on differentiation of oligodendrocyte precursor cells in vitro, and the relationship between BMP-4 and Olig2.To provide experimental basis for the mechanism of no myelin sheath in retina and optic papilla and to provide new ideas for the treatment of related myelin diseases.Methods Immunohistochemical staining was used to detect the expression and distribution of BMP-4 in retina and optic papilla.Oligodendrocyte precursor cells were isolated and purified by isothermal oscillation and differential adherent method, and the effects of BMP-4 on differentiation and development of oligodendrocyte precursor cells were studied.The relationship between BMP-4 and Olig2 is studied by Western Blot.Results BMP-4 was only selectively expressed in the optic papilla during development.Oligodendrocyte progenitor cells were successfully purified. After removing the proliferating factor from the culture medium, oligodendrocyte progenitor cells spontaneously differentiated and matured into oligodendrocytes, but after adding BMP-4, the oligodendrocyte progenitor cells spontaneously differentiated and matured into oligodendrocytes.The differentiation direction of oligodendrocyte precursor cells changed, and high concentration of BMP-4 resulted in the differentiation of oligodendrocyte precursor cells into type 鈪，

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