Genomic of Olfactory Regeneration

嗅觉再生基因组

基本信息

批准号：
7367068
负责人：
Timothy S McClintock
金额：
$ 30.7万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-01 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7367068
关键词：
Abbreviations Adult Affect Afferent Neurons Analysis of Variance Animals Axon Basal Cell CDKN1A gene Cell Cycle Cell Proliferation Cells Cessation of life Data Set Development Differentiation and Growth Embryo Epithelium 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 Neuro-Oncological Ventral Antigen 2 Neurodegenerative Disorders Neurons Neurosciences Research Numbers 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 Week Work cell type day human ASCL1 protein interest mutant neurodevelopment neurogenesis null mutation olfactory bulb olfactory marker protein oncoprotein p21 postnatal progenitor programs protein function receptor 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.

即使完全消除了嗅觉上皮的感觉神经元，也可以再生。这种能力在动物的整个生命中持续下去，并且对基本和应用都具有重大兴趣神经科学研究。它的机制被认为与寻找再生有关促进神经退行性疾病和神经系统创伤的疗法。它的机制也显然与神经发展有关。为了扩展我们对嗅觉再生的理解，我们已经确定了1,205个mRNA，其在嗅觉上皮内的丰度在去除后变化嗅球，这种操纵导致选择性死亡和随后的嗅觉再生感觉神经元。在这些mRNA中，303随着感觉的增殖而同时增加神经元祖细胞。这303个mRNA编码的蛋白质功能预测了几种基础过程，包括细胞增殖和分化的转录激活，细胞上调循环，轴突产物和细胞信号传导。以前只有少数这些蛋白质与嗅觉再生或发展。在此应用中，我们建议专注于基因产品的一部分这对于嗅觉感觉神经元的增殖和分化可能至关重要。第一个具体目的是定义每种基因产物参与嗅觉再生的能力确定哪种细胞类型表达它们，包括与已知标记的空间和时间重叠祖细胞类型。第二和第三目的进一步集中于针对性的基因子集删除可用。这些目的测试基因缺乏是否改变了发展或嗅觉上皮的再生，导致细胞或分子水平的变化。提议实验将确定测试几种蛋白质是否具有嗅觉开发和再生，并将定义几十个其他蛋白质的潜在作用。