Regulation of Olfactory Receptor Neuronal Cell-Cycle

嗅觉受体神经元细胞周期的调节

• 批准号: 6876673
• 负责人: P JEANETTE SIMPSON
• 金额: $ 8.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6876673
• 关键词: atrial natriuretic peptide; biological signal transduction; brain derived neurotrophic factor; cell cycle; cell cycle proteins; cell differentiation; cell growth regulation; cell proliferation; chemoreceptors; laboratory rat; nerve growth factors; neurogenesis; olfactions; protein biosynthesis; transcription factor; western blottings

DESCRIPTION (provided by applicant): The understanding of cell-cycle control during postnatal neurogenesis has become increasingly interesting with the finding of postnatal stem cells in the adult brain. We have used the olfactory system as a model system for studying the mechanisms involved in postnatal neurogenesis. We have identified several factors that regulate proliferation and differentiation in olfactory receptor neuron (ORN) precursor cells. Two of these factors, which cause proliferation, are members of the neurotrophin family, BDNF and NGF. A third factor, which antagonizes BDNF- and NGF-induced proliferation and promotes maturation of ORNs to the next developmental stage, is a member of the atrial natriuretic peptide family, C-type atrial natriuretic peptide (CNP). This work seeks to further research into the mechanisms of action used by these factors, focusing mostly on BDNF and CNP, to exert their effects on cell-cycle regulation. We will look at their effects as individual factors and also explore the effects of their interactions. We propose to accomplish this through the completion of two broad specific aims. Aim I is to determine the effects of BDNF and CNP, both alone and together, on levels of various cell-cycle regulatory proteins. We will also seek to determine the role of protein synthesis in regulation of these proteins and determine which of a select set of transcription factors may be involved. Aim II will focus on unraveling the signal transduction mechanisms used by BDNF and CNP to exert their effects. These experiments should provide valuable information regarding the potential effects of BDNF and CNP in neurogenesis, and also provide more general information on cell-cycle regulation in the postnatal neuron.

描述（由申请人提供）：随着在成人大脑中发现产后干细胞，对产后神经发生过程中细胞周期控制的理解变得越来越有趣。我们使用嗅觉系统作为研究出生后神经发生机制的模型系统。我们已经确定了调节嗅觉受体神经元（ORN）前体细胞增殖和分化的几种因素。其中两个导致增殖的因子是神经营养蛋白家族的成员：BDNF 和 NGF。第三个因子是心房钠尿肽家族的成员，即 C 型心房钠尿肽 (CNP)，它可以拮抗 BDNF 和 NGF 诱导的增殖并促进 ORN 成熟到下一个发育阶段。这项工作旨在进一步研究这些因子的作用机制，主要关注 BDNF 和 CNP，以发挥它们对细胞周期调节的影响。我们将把它们作为个体因素的影响来看待，并探讨它们相互作用的影响。我们建议通过完成两个广泛的具体目标来实现这一目标。目标 I 是确定 BDNF 和 CNP 单独或共同使用对各种细胞周期调节蛋白水平的影响。我们还将寻求确定蛋白质合成在这些蛋白质的调节中的作用，并确定可能涉及一组选定的转录因子中的哪一个。 Aim II 将重点揭示 BDNF 和 CNP 发挥作用的信号转导机制。这些实验应该提供关于 BDNF 和 CNP 在神经发生中的潜在影响的有价值的信息，并且还提供关于出生后神经元的细胞周期调节的更一般的信息。