Genomic of Olfactory Regeneration

嗅觉再生基因组

基本信息

批准号：
7857725
负责人：
Timothy S McClintock
金额：
$ 7.49万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-17 至 2010-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7857725
关键词：
Abbreviations Adult Affect Afferent Neurons Analysis of Variance Animals Axon Basal Cell Cell Cycle Cell Proliferation Cells Cessation of life Data Set Development Differentiation and Growth Embryo Erinaceidae Excision Fibroblast Growth Factor Fluorescent in Situ Hybridization Galactosidase Genes Genomics Green Fluorescent Proteins Growth Associated Protein 43 Helix-Turn-Helix Motifs Knockout Mice LacZ Genes Life Link Measures Messenger RNA Methods Molecular Mouse Strains Mus Natural regeneration Nervous System Trauma Neurodegenerative Disorders Neurons Neurosciences Research Odorant Receptors Olfactory Epithelium Pattern Play Polymerase Chain Reaction Process Proteins Research Personnel Reverse Transcriptase Polymerase Chain Reaction Reverse Transcription Role Series Signal Transduction Signaling Protein Stem cells Testing Time Transcript Transcription factor genes Transcriptional Activation Up-Regulation Work cell type human ASCL1 protein interest mutant neurodevelopment neurogenesis neuron development null mutation olfactory bulb olfactory marker protein postnatal progenitor programs protein function receptor expression research study response sustentacular cell transcription factor

项目摘要

The sensory neurons of the olfactory epithelium can be regenerated even if they are completely eliminated. This capacity lasts throughout the life of the animal and is of significant interest for both basic and applied neuroscience research. Its mechanisms are presumed to be relevant to the search for regeneration- promoting therapies for neurodegenerative disorders and trauma of the nervous system. Its mechanisms are also clearly relevant to neural development. To extend our understanding of olfactory regeneration, we have identified 1,205 mRNAs whose abundance within the olfactory epithelium changes after removal of the olfactory bulbs, a manipulation that causes the selective death and subsequent regeneration of the olfactory sensory neurons. Of these mRNAs, 303 increase contemporaneously with the proliferation of sensory neuron progenitors. The functions of the proteins encoded by these 303 mRNAs predict several underlying processes, including transcriptional activation of cell proliferation and differentiation, up-regulation of the cell cycle, axon outgrowth, and cell signaling. Only a handful of these proteins have previously been linked to olfactory regeneration or development. In this application, we propose to focus on a subset of gene products that are likely to be critical for proliferation and differentiation of the olfactory sensory neurons. The first specific aim is to define the capacity for each gene product to be involved in olfactory regeneration by determining which cell types express them, including spatial and temporal overlap with markers of known progenitor cell types. The second and third aims focus further on a subset of genes for which targeted deletions are available. These aims test whether the absence of the gene alters the development or regeneration of the olfactory epithelium, leading to changes at the cellular or molecular level. The proposed experiments will definitively test whether several proteins are dispensable for olfactory development and regeneration, and will define the potential roles of a couple dozen additional proteins.

嗅觉上皮的感觉神经元即使完全消除也可以再生。这种能力持续动物的一生，对于基础和应用都具有重要意义。神经科学研究。据推测其机制与寻找再生有关促进神经退行性疾病和神经系统创伤的治疗。其机制也明显与神经发育相关。为了扩展我们对嗅觉再生的理解，我们已经鉴定出 1,205 个 mRNA，其在嗅觉上皮细胞中的丰度在去除嗅球，一种导致嗅觉选择性死亡和随后再生的操作感觉神经元。在这些 mRNA 中，有 303 个随着感觉细胞的增殖而同时增加。神经元祖细胞。这 303 个 mRNA 编码的蛋白质的功能预测了一些潜在的过程，包括细胞增殖和分化的转录激活、细胞的上调周期、轴突生长和细胞信号传导。这些蛋白质中只有少数以前与嗅觉再生或发育。在此应用中，我们建议重点关注基因产物的子集这可能对嗅觉感觉神经元的增殖和分化至关重要。第一个具体目标是通过以下方式确定每个基因产物参与嗅觉再生的能力确定哪些细胞类型表达它们，包括与已知标记物的空间和时间重叠祖细胞类型。第二个和第三个目标进一步关注目标基因的子集可以进行删除。这些目的测试基因的缺失是否会改变发育或嗅上皮的再生，导致细胞或分子水平的变化。拟议的实验将明确测试几种蛋白质对于嗅觉发育是否是可有可无的再生，并将定义几十种其他蛋白质的潜在作用。