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和 将修饰剂植入原始神经组织。在这些研究过程中， 观察到的现象暗示着超乎寻常的可塑性 发育迟缓的未成熟的神经系统。这项研究建议 努力确定这些现象的普遍性，并理解 指导这种可塑性以开发其潜力的变量是 发育性神经损伤的预防、补偿与修复 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，但也发展成“出了问题”--也就是， 不受控制的可塑性--这可能被证明是一种分子机制 有助于神经肿瘤的发生。体外和活体研究将继续进行 在老鼠身上。在体外，“永生”基因被植入个体 神经干细胞--既有神经管(小脑)，也有神经脊 起源--通过建立神经细胞系，研究 R 随后的差异化和承诺。在小脑，线条来自 表面上不同的神经细胞类型似乎不仅是 克隆性相关，但在其表达中表现出可塑性 表型。在这一系统中的工作将寻求确定哪些因素 直接向下区分给定的表型路径或允许选定的 表型发生改变，并利用这些品系进行神经移植。 神经脊的线条将被类似地刻画，稍后进行搜索 VS早期承诺，评估可塑性程度，并作为 移植材料。在体内，通过微量注射载体 将“标记”基因导入新生和胚胎小鼠小脑中 胚胎小鼠视网膜，单个祖细胞已经被标记在s 使用 允许进行谱系映射。正在得出两个结论：(A)多发性NeuRA 细胞类型出现在一个给定的克隆中，这表明它们共享一个逗号 发散到最后一次细胞分裂的祖细胞(视网膜)； 中枢神经系统中的多能祖细胞可能迁移到细胞类型 只有在与其微环境相互作用之后才会发生 (出生后小脑)。出生前和出生后小脑的谱系模式 将被分析以验证这些印象，并为 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.