Genomic of Olfactory Regeneration

嗅觉再生基因组

• 批准号: 7844580
• 负责人: Timothy S McClintock
• 金额: $ 0.98万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7844580
• 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

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.

嗅上皮的感觉神经元即使被完全清除，也可以再生。 这种能力持续整个生命的动物，是重大利益的基础和应用 神经科学研究。它的机制被认为与再生的研究有关- 促进神经系统变性疾病和创伤的治疗。其机制 显然也与神经发育有关为了扩展我们对嗅觉再生的理解，我们 已经鉴定了1，205种mRNA，其在嗅上皮中的丰度在去除嗅上皮后发生了变化。 嗅球，一种导致嗅觉器官选择性死亡和随后再生的操作。 感觉神经元在这些mRNAs中，303个随着感觉神经细胞的增殖而同时增加。 神经元祖细胞由这303种mRNA编码的蛋白质的功能预测了几种潜在的 过程，包括细胞增殖和分化的转录激活，细胞增殖和分化的上调， 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。在本申请中，我们建议关注基因产物的子集 这可能是至关重要的增殖和分化的嗅觉感觉神经元。第一 具体的目的是通过以下方式来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，包括与已知的细胞类型的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 删除是可用的。这些目的是测试基因的缺失是否会改变发育， 嗅觉上皮的再生，导致细胞或分子水平的变化。拟议 实验将明确测试几种蛋白质是否与嗅觉发育有关， 再生，并将确定几十个额外的蛋白质的潜在作用。