PROGRAMS OF GENE EXPRESSION IN OLFACTORY NEUROGENESIS

嗅觉神经发生中的基因表达程序

• 批准号: 7900794
• 负责人: JOHN J. NGAI
• 金额: $ 20.23万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-14 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7900794
• 关键词: Adult; Afferent Neurons; Axon; Biological; Cells; Complex; DNA Microarray Chip; Data Set; Development; Embryonic Development; Environment; Gene Expression; Generations; Genes; Genetic; Genetic Programming; Human Genome; In Situ Hybridization; Individual; Lead; Lesion; Life; Microarray Analysis; Molecular Profiling; Monitor; Multipotent Stem Cells; Mus; Mutant Strains Mice; Natural regeneration; Nervous system structure; Neuraxis; Neurons; Neurophysiology - biologic function; Olfactory Epithelium; Pathway interactions; Pattern; Process; Property; RNA; Series; Staging; Stem cells; Synapses; System; Techniques; Time; Transcript; Validation; base; cell motility; cell type; complex biological systems; genome-wide; insight; molecular marker; mutant; nerve stem cell; neurogenesis; progenitor; programs; relating to nervous system; research study

The generation of neuronal diversity in the nervous system is a complex process involving the specification and differentiation of a multitude of cellular lineages. Successive developmental programs control the determination and proliferation of individual neuronal types, cell migration, axon extension, and ultimately the formation of functional synaptic connections. Most of these steps are controlled by specific gene expression programs, such as cell fate decisions that lead to the generation of neuronal precursors. The genetic programs underlying the differentiation of mature neurons from their progenitors remain largely unknown, however, in part because of the difficulty in studying neuronal stem cells in their native environments. In the vertebrate olfactory system, primary sensory neurons are continuously regenerated throughout adult life via the proliferation and differentiation of neural progenitor cells. This feature makes the olfactory system particularly amenable for studies on the properties of neuronal stem cells. While some stages of this lineage have been identified with a limited set of molecular markers, the genetic programs that both define and regulate olfactory neurogenesis remain largely unknown. The enormous complexity inherent in this biolo,qical _roblem demands a .qlobal view of .qene expression in order to fully understand the ,qenetic networks Jnderlyin.q neural function and development in this developmental system. In this application we propose a suite of DNA microarray-based techniques to identify - on a ,qlobal scale - patterns of .qene expression correspondin.q to distinct sta.qes of the olfactory neuron linea,qe. We propose (1) to perform temporal profiling of gene expression in olfactory epithelium during embryonic development and lesion-induced regeneration to identify the genes and gene expression programs associated with distinct stages of this lineage, including the earliest multipotent progenitor stage; and (2) to refine this analysis by comparing gene expression patterns in mutants known to disrupt olfactory neurogenesis, and to validate the microarray-based predictions by RNA in situ hybridizations. Our approach is expected to yield highly detailed information about the molecules and pathways responsible for the genesis of olfactory sensory neurons from their progenitor cells. In addition, a broader panel of molecular markers will be generated for distinct stages of olfactory neurogenesis. The elucidation of these ,qenetic pro,qrams at the ,qenome-wide level will provide valuable insi.qhts into the properties of pro,qenitor stem cells from a variety of neural and non-neural systems.

神经系统中神经元多样性的产生是一个涉及规范的复杂过程 和多种细胞谱系的分化。连续的发展计划控制 单个神经元类型，细胞迁移，轴突延伸的确定和增殖，最终 功能突触连接的形成。这些步骤中的大多数都由特定的基因表达控制 程序，例如导致神经元前体产生的细胞命运决策。遗传 成熟神经元与祖细胞差异化的基础的程序仍然很大未知， 但是，部分原因是在其天然环境中很难研究神经元干细胞。 在脊椎动物嗅觉系统中，原发性感觉神经元在整个成年人中连续再生 通过神经祖细胞的增殖和分化生命。此功能使嗅觉系统 特别适合研究神经元干细胞的特性。虽然这个血统的某些阶段 已经确定了一组有限的分子标记物，这是定义和定义的遗传程序 调节嗅觉神经发生在很大程度上未知。这个Biolo固有的巨大复杂性 _问题需要一个.qlobal的视图。 Jnderlyin.Q神经功能和发育中的发展系统。 在此应用中，我们提出了一套基于DNA微阵列的技术，以在Qlobal量表上识别 - .qene表达的模式对应于QE的嗅觉神经元线的不同sta.qes。我们提出（1） 在胚胎发育期间对基因表达进行嗅觉表达的时间分析 病变引起的再生，以识别与不同的基因和基因表达程序 该血统的阶段，包括最早的多能祖细胞阶段； （2）通过 比较已知破坏嗅觉神经发生的突变体中的基因表达模式，并验证 RNA原位杂交基于微阵列的预测。 我们的方法有望产生有关负责分子和途径的高度详细信息 对于来自祖细胞的嗅觉感觉神经元的起源。另外，更广泛的面板 分子标记将用于嗅觉神经发生的不同阶段。阐明这些 ，Qenetic Pro，QRAMS在Qenome范围内，将为Pro，Qenitor的属性提供有价值的Insi.qhts 来自多种神经和非神经系统的干细胞。