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 在整个成年生活中继续。 在任何不断更新的组织中， 总细胞数的“稳态”是通过细胞间的平衡实现的。 增殖和细胞死亡。 这意味着：1）细胞的速率 增殖受到调节，2）细胞死亡的速率受到调节，以及 3)细胞增殖和细胞死亡的调节因子是 有联系 本提案的总体目标是审查几个方面 细胞增殖和细胞死亡。 早些时候 实验表明，嗅觉细胞的增殖可以增加， 通过实验操作下调。 初步数据显示 两种生长因子，表皮生长因子（EGF）和转化生长 因子-α（TGF-α）在体外细胞增殖的上调中的作用 比色法 这两个都是所谓的EGF家族的成员增长 因素 EGF家族的成员是 生长因子参与嗅觉细胞有丝分裂率的调节 上皮 这项建议是一个多学科的办法， 嗅感觉上皮细胞动力学的研究。 一个目的 EGF家族的生长因子及其 同源受体是调节的功能参与者， 嗅觉（或支持）细胞在体外和体内的增殖。 另一个目的是测试其他生长因子在以下方面的功效： 促进嗅上皮的增殖。 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 维持的是细胞死亡的调节。 非常少的细节 关于细胞死亡机制的信息是可用的， 嗅觉系统 这项建议的一部分是为了获得一些 基线信息;例如，细胞的电子显微镜研究 嗅球消融后死亡， 关于发生的特定形态变化的详细信息 在垂死的细胞，并确定他们的处置方式。 的 关于其他系统中细胞死亡的文献表明， 生物化学事件在大部分时间都是在细胞中观察到的， 被设定为死亡 用于鉴定细胞死亡标志物的探针 在其他组织中，将用于指定生物化学和 嗅觉细胞死亡的组织化学标志物。 最后，生长因子 将通过微泵注入单侧球切除大鼠 试图拯救注定死亡的嗅觉细胞的装置。

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.