USE OF RETROVIRAL VECTORS TO STUDY NEURAL PLASTICITY

阐明指导哺乳动物神经发育的机制 系统中，逆转录病毒载体用于插入可遗传的遗传标记， 原始神经组织中的修饰物。 在这些研究的过程中， 观察到的现象暗示着一种非凡的可塑性 在未成熟的神经系统发育后期。 建议的研究 努力确定这些现象的普遍性， 引导这种可塑性以开发其潜力的变量是 对受损发育神经的预防、补偿和修复 系统 这样的理解不仅可以让我们深入了解 正常的神经发育，但也进入发展"出了问题"-即， 不受限制的可塑性--这可能是一种分子机制 导致神经肿瘤的发生 将继续进行体外和体外研究 在老鼠。 在体外，"永生"基因被插入到个体中， 神经干细胞-神经管（小脑）和神经嵴 起源--通过创建神经细胞系，可以研究 R 随后的差异化和承诺。 在小脑中， 表面上不同的神经细胞类型似乎不仅 克隆相关，但在其表达中表现出可塑性， 表型。 这一系统的工作将设法确定 直接分化下给定的表型路径或允许选择 表型改变，并使用这些线的神经移植。 来自神经嵴的线将被类似地表征，晚些时候搜索 与早期承诺相比，评估可塑性程度，并作为 移植材料 体内，通过载体的显微注射 含有"标记"基因的新生和胚胎小鼠小脑， 胚胎小鼠视网膜，单个祖细胞已被标记， u 允许谱系映射。 两个结论正在出现：（a）多神经元 细胞类型存在于一个给定的克隆中，这表明它们有一个共同点， 迟至最后一次细胞分裂的分化祖细胞（视网膜）;（B） CNS中的多能祖细胞可以迁移并定型为细胞类型 只在与微环境相互作用后发生 （出生后小脑）。 出生前后小脑的谱系模式 将进行分析，以验证这些印象，并提供基础， 移植实验

To elucidate mechanisms which direct development of the mammalian nervous system, retroviral vectors are used to insert heritable genetic markers and modifiers into primordial neural tissue. In the course of these studies, phenomena were observed which hint at an extraordinary degree of plasticity late in development of the immature nervous system. The studies proposed endeavor to determine the pervasiveness of these phenomena and to understan the variables directing this plasticity in order to exploit its potential i the prevention, compensation, and repair of the damaged developing nervous system. Such an understanding may not only lend insight into strategies of normal neural development, but also into development "gone awry"--i.e., unchecked plasticity--which may prove to be a molecular mechanism contributing to neural oncogenesis. Work will continue IN VITRO and IN VIV in the mouse. IN VITRO, "immortalizing" genes are inserted into individual neural stem cells--both of neural tube (cerebellum) and neural crest origin--allowing, through the creation of neural cell lines, a study of the r subsequent differentiation and commitment. In cerebellum, lines from ostensibly different neural cell types appear not only to be clonally-related, but to display plasticity in the expression of their phenotype. Work in this system will seek to determine the factors which direct differentiation down a given phenotypic path or allow a selected phenotype to change, and to use these lines for neural transplantation. Lines from neural crest will be similarly characterized, searched for late vs early commitment, assessed for degrees of plasticity, and serving as transplantation material. IN VIVO, through microinjection of vectors containing "marker" genes into neonatal and embryonic mouse CEREBELLUM and embryonic mouse RETINA, individual progenitor cells have been labeled in si u allowing lineage mapping. Two conclusions are emerging: (a) multiple neura cell types are present in a given clone, suggesting that they share a commo progenitor with divergence as late as the last cell division (retina); (b) multipotent progenitors in the CNS may migrate with commitment to cell type occurring only later, following interaction with its microenvironment (postnatal cerebellum). Lineage patterns in pre- and postnatal cerebellum will be analyzed to validate these impressions and provide a basis for transplantation experiments.