Olfactory Development: Cell Proliferation and Maturation

这个项目的总体目标是了解是什么调节了胚胎后再生 嗅觉外周。这项提案侧重于该项目的一个主要方面--新的 成年动物的嗅觉感受器神经元和相关细胞。持续的扩散和周转 嗅觉感受器神经元，即使在成人身上，也是人类的一个特征，在动物模型中也有表达 在这项研究中使用。这三个具体的施舍是：1)哪些基因与新生血管的增殖有关 嗅觉细胞？2)局部和激素因素如何改变嗅觉细胞的增殖？和3)什么 嗅觉细胞的增殖、成熟和分化与功能改变有关？至 调查这些问题，这项提案将利用龙虾嗅觉系统的关键优势特征， 其中包括关于这个系统的职能组织的丰富知识，连续的人员更替 成年嗅觉组织，可受损伤和荷尔蒙(如哺乳动物)调节，以及发育中的 轴到嗅觉器官，在那里有物理上的增殖区、成熟区和衰老区 分开的(哺乳动物中不是这样)。因此，这些实验在龙虾身上是可能的，但在其他地方是不可能的 突出的无脊椎动物模型，如果蝇和线虫，它们缺乏胚胎后代谢 嗅觉神经元。实验设计将包括分子技术，包括搜索小说 基因(通过代表性差异分析)和同源基因(通过RT-PCR)，表达分析 基因及其产物的模式(通过原位杂交和免疫细胞化学)，以及分析 功能(通过膜片钳和单细胞电生理学)。这些干细胞样活性的研究和 胚胎后成年动物的神经发生很重要，因为这些再生过程不仅是 对了解感觉器官的功能调节具有基本的重要性，也具有实用性 帮助我们了解如何通过监管来补偿活动和功能损失的重要性 由控制系统控制。

The overall goal of this project is to understand what regulates the post-embryonic regeneration of the olfactory periphery. This proposal focuses on one major aspect of the project - the proliferation of new olfactory receptor neurons and associated cells in adult animals. Continuous proliferation and turnover of olfactory receptor neurons, even in adults, is a feature of humans that is also expressed in the animal model used in this study. The three specific alms are 1) What genes are associated with proliferation of new olfactory cells? 2) How do local and hormonal factors alter proliferation of olfactory cells? and 3) What functional changes are correlated with proliferation, maturation, and differentiation of olfactory cells? To investigate these issues, this proposal will use critical advantageous features of the lobster olfactory system, which include a wealth of knowledge about the functional organization of this system, continuous turnover of adult olfactory tissue that can be modulated by damage and hormones (as in mammals), and a developmental axis to its olfactory organ in which the zones of proliferation, maturation, and senescence, are physically separated (not so in mammals). Consequently, these experiments are possible in the lobster, but not in other prominent invertebrate models such as Drosophila and C. elegans which lack post-embryonic turnover of olfactory neurons. The experimental design will include molecular techniques including searches for novel genes (by representational difference analysis) and homologous genes (by RT-PCR), analysis of expression patterns of genes and their products (by in-situ hybridization and immunocytochemistry), and analysis of function (by patch-clamp and single cell electrophysiology). These studies of stem cell-like activity and neurogenesis in post-embryonic adult animals are important since these regenerative processes are not only of basic importance to understanding regulation of function of a sensory organ, but also have the practical importance of helping us understand how to compensate for loss of activity and function through regulation by control systems.