MIGRATION AND DIFFERENTIATION OF NEURONS IN ADULT MAMMAL

描述：神经元的产生、迁移和分化 在很大程度上被认为是一个发展过程， 出生 最近的研究表明，成年哺乳动物的中枢神经系统含有一个 室管膜下区（SVZ）的分裂前体细胞群 侧脑室，这是能够形成新的神经元， 体外 神经元前体细胞永久存在的生物学原因 成年哺乳动物中枢神经系统中的细胞是未知的。 概述的实验 在这项建议中，旨在详细调查 SVZ细胞在成年小鼠中的增殖。 小块的分裂 SVZ细胞将用3H-胸苷、DiI或 转基因小鼠的组织移植。 的途径 标记细胞的迁移将被绘制成图表，并且成熟的表型 来自分裂群体的神经元的特征将是 测定 此外，超微结构的分裂和成熟，新 将检查细胞。 将成人SVZ组织移植到 胚胎或新生儿宿主将被用于评估这种 异时环境可以诱导成年SVZ细胞形成 通常只在发育早期产生的神经元。 最后， 实验策略，以确定是否成人SVZ细胞 可以替代中枢神经系统损伤的神经元。 表征 这些干细胞在成年人中的发育潜力 哺乳动物中枢神经系统是确定潜在的 这些细胞用于损伤或疾病后的脑修复。

DESCRIPTION: The generation, migration and differentiation of neurons is largely considered a developmental process that ends soon after birth. Recent studies have shown that adult mammalian CNS contains a population of dividing precursor cells in the subventricular zone (SVZ) of the lateral ventricles, which are capable of forming new neurons in vitro. The biological reasons for the permanence of neuronal precursor cells in the CNS of adult mammals is unknown. The experiments outlined in this proposal are designed to investigate in detail the fate of the proliferating SVZ cells in the adult mouse. Small patches of dividing SVZ cells will be labeled either with 3H-thymidine, DiI, or by transplantation of tissue from transgenic mice. The pathways of migration of labeled cells will be charted, and the mature phenotypic characteristics of neurons derived from the dividing population will be determined. In addition, the ultrastructure of dividing and mature, new cells will be examined. Transplantation of adult SVZ tissue into embryonic or neonatal hosts will be used to assess whether such heterochronic environments can induce SVZ cells from adults to form neurons that are normally produced only early in development. Finally, experimental strategies are presented to determine if adult SVZ cells can replace neurons damaged by lesions in the CNS. The characterization of the developmental potential of these stem cells in the adult mammalian CNS is an important first step in determining the potential use of these cells for brain repair following injury or disease.