Cell migration and differentiation in the olfactory bulb

描述(由申请人提供)：脑室下区(SVZ)的神经干细胞在整个发育过程中和成人中参与新细胞的持续生成。这些新形成的细胞的主要目标是嗅球。这些SVZ祖细胞沿着吻端迁移流从SVZ迁移到嗅球。在嗅球中，这些细胞径向迁移到不同的层，并分化为主要的中间神经元，尽管也被认为是产生了胶质细胞。指导这些细胞分化的线索，以及它们在嗅球中径向迁移的许多机制，目前尚不清楚。 本研究的目的是研究SVZ前体细胞在嗅球内的迁移和分化。目的1通过器官切片培养，确定SVZ祖细胞在不同发育阶段的迁移所衍生的细胞表型，以及这些细胞的命运是否会受到环境因素的干扰。目的2研究SVZ前体细胞沿吻端游走流向嗅球迁移的机制。这些实验侧重于迁移神经元与出生后和成人中存在的不同可能的迁移支架之间的关系，以及基质金属蛋白酶在促进这些细胞迁移中所起的作用。了解SVZ祖细胞通过嗅球迁移的机制和控制表型选择的线索对于将这些细胞用于临床治疗具有重要意义。

DESCRIPTION (provided by applicant): Neural stem cells in the subventricular zone (SVZ) are involved in the continual generation of new cells throughout development and in adult. The major target of these newly formed cells is the olfactory bulb. These SVZ progenitors migrate from the SVZ along the rostral migratory stream and into the olfactory bulb. In the olfactory bulb these cells migrate radially to different layers and differentiate into primarily interneurons, although glia are also thought to be generated. The cues directing the differentiation of these cells, and many of the mechanisms involved in their radial migration in the olfactory bulb, are unclear. This goal of this research is to investigate the migration and differentiation of SVZ progenitors in the olfactory bulb. Aim 1 will determine what cell phenotypes are derived from SVZ progenitor migration at different developmental stages, and whether the fate of these cells can be perturbed by environmental cues using organotypic slice culture. Aim 2 investigates the mechanisms used by SVZ progenitors to migrate along the rostral migratory stream and into the olfactory bulb. These experiments focus upon the relationship between migrating neurons and different putative migratory scaffolds present in postnatal and adult, and the role that matrix metalloproteinases may have in facilitating the migration of these cells. Understand the mechanisms of SVZ progenitor migration through the olfactory bulb and cues governing phenotype selection have important implications for the use of these cells as clinical therapy.