EARLY DEVELOPMENT OF OLFACTORY RECEPTOR ORGAN

脊椎动物嗅觉系统中新感觉神经元的产生 在整个成年生活中继续。 本建议的总体目标是 检查嗅上皮细胞增殖的几个方面。 早期的实验表明，嗅觉细胞的增殖可能是 通过实验操作进行上调和下调。初步数据 从体外实验表明，三种生长因子，表皮 生长因子（EGF）、转化生长因子-α（TGF-α）和 双调蛋白（AR）可上调细胞增殖速率。这些 生长因子是EGF家族的成员。 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 这一假设得到了我们的生物化学和 免疫组化数据鉴定EGF受体的存在， 嗅上皮的基底细胞（有丝分裂细胞）。EGF和 TGF-α被认为是该受体的配体。这项建议 代表了一种多学科的方法来研究细胞 嗅感觉上皮细胞增生。一个目的是 EGF家族的生长因子及其同源物 受体是调节感觉（或神经）的功能参与者。 支持）细胞增殖。另一个目的是 测试其他生长因子在促进增殖方面的功效 在嗅上皮中。第三个目的是使用渗透微泵， 实验动物递送少量的生长因子（或 抗体与生长因子）直接接触嗅粘膜， 局部刺激（或抑制）细胞增殖。 几 技术，包括器官培养，免疫组织化学，电子显微镜， 显微镜，原位杂交和生物化学将用于这些 实验

Production of new sensory neurons in the vertebrate olfactory system continues throughout adult life. The overall aim of this proposal is to examine several aspects of cell proliferation in olfactory epithelium. Earlier experiments had shown that olfactory cell proliferation can be up- and down-regulated by experimental manipulations. Preliminary data from in vitro experiments show that three growth factors, Epidermal Growth Factor (EGF), Transforming Growth Factor-alpha (TGF-alpha) and amphiregulin (AR), can up-regulate the rate of cell proliferation. These growth factors are 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. The hypothesis is supported by our biochemical and immunohistochemical data identifying the presence of EGF receptor in basal cells (the mitotic cells) of olfactory epithelium. Both EGF and TGF-alpha are presumed to be ligands for this receptor. This proposal represents a multidisciplinary approach to the study of cellular proliferation 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 sensory (or supporting) cell proliferation both in vitro and in vivo. Another aim is to test other growth factors their efficacy in enhancing proliferation in olfactory epithelium. A third aim is to use an osmotic micropump in experimental animals to deliver small quantities of growth factor (or antibody vs growth factor) directly to the olfactory mucosa to try to stimulate (or inhibit) cellular proliferation locally. Several techniques, including organ culture, immunohistochemistry, electron microscopy, in situ hybridization and biochemistry will be used in these experiments.