PROLIFERATION AND CELL DEATH IN OLFACTORY EPITHELIUM

在脊椎动物嗅觉系统中产生新的感觉神经元 在整个成年生活中持续存在。在任何持续更新的组织中 细胞总数的“稳定状态”是通过细胞间的平衡来实现的 增殖和细胞死亡。这意味着：1)细胞比率 增殖受到调控，2)细胞死亡率受到调控，以及 3)细胞增殖和细胞死亡的调节因子是 已链接。这项提案的总体目标是研究以下几个方面 嗅觉上皮细胞的增殖和死亡。早些时候 实验表明，嗅觉细胞的增殖能力可以增强 被实验操作下调了。初步数据显示 两种生长因子：表皮生长因子与转化生长 转化生长因子-α在体外上调细胞增殖中的作用 化验。这两个人都是所谓的EGF增长家族的成员 各种因素。工作假说是EGF家族的成员 生长因子参与调节嗅觉细胞有丝分裂速率 上皮组织。这项提议代表了一种多学科的方法来解决 嗅觉上皮细胞动力学的研究。一个目标 是为了确定EGF家族的生长因子及其 同源受体是参与调节的功能参与者。 嗅觉(或支持)细胞在体外和体内的增殖。 另一个目标是测试其他生长因子在 促进嗅觉上皮细胞增殖。几种技术， 包括器官培养、免疫组织化学、电子显微镜、 在这些实验中将使用原位杂交和生物化学。 嗅觉细胞数量的另一个方面是 维持的是细胞死亡的调节。细节很少 有关细胞死亡机制的信息可在 嗅觉系统。这项提案的一部分旨在获得一些 基线信息；例如，细胞的电子显微镜研究 消融嗅球后的死亡将被做为 有关发生的特定形态变化的详细信息 并确定处理它们的方法。这个 关于其他系统中细胞死亡的文献表明，某些 在大多数情况下，可以在细胞中观察到生化事件 被设定为死亡。细胞死亡标记物鉴定的探讨 在其他组织中将被用来指定生化和 嗅觉细胞死亡的组织化学标志物。最后是增长因素 将通过微泵注入单侧球部切除的大鼠体内 试图挽救注定要死亡的嗅觉细胞的设备。

In the vertebrate olfactory system production of new sensory neurons continues throughout adult life. In any continuously renewing tissue a "steady state" in total cell number is achieved by a balance between cell proliferation and cell death. This implies that: 1) the rate of cell proliferation is regulated, 2) the rate of cell death is regulated, and 3) the regulating factors for cell proliferation and cell death are linked. The overall aim of this proposal is to examine several aspects of cell proliferation and cell death in olfactory epithelium. Earlier experiments had shown that olfactory cell proliferation can be up-and down-regulated by experimental manipulations. Preliminary data implicate two growth factors, Epidermal Growth Factor (EGF) and Transforming Growth Factor-a (TGF-a), in up-regulation of cell proliferation in an in vitro assay. These are both members of what is called the EGF family of growth factors. The working hypothesis is that members of the EGF family of growth factors participate in the regulation of mitotic rate in olfactory epithelium. This proposal represents a multidisciplinary approach to the study of cellular dynamics in the olfactory sensory epithelium. One aim is to determine whether the EGF family of growth factors and their cognate receptors are functional participants in the regulation of olfactory (or supporting) cell proliferation both in vitro and in vivo. Another aim is to test other growth factors for their efficacy in enhancing proliferation in olfactory epithelium. Several techniques, including organ culture, immunohistochemistry, electron microscopy, in situ hybridization and biochemistry will be used in these experiments. The other aspect of how the olfactory cell population numbers are maintained is the regulation of cell death. Very little detailed information is available about the mechanism of cell death in the olfactory system. Part of this proposal is designed to obtain some baseline information; for example, electron microscope studies on cell death following ablation of the olfactory bulb will be done to acquire detailed information about the specific morphological changes that occur in dying cells and to determine the means for their disposal. The literature on cell death in other systems suggests that certain biochemical events are observable most of the time in cells that are programmed to die. Probes for the identification of cell death markers in other tissues will be used to specify the biochemical and histochemical markers for olfactory cell death. Finally growth factors will be infused into unilaterally bulbectomized rats by a micropumping apparatus to try to rescue olfactory cells that are destined to die.