Identification of Synaptic remodeling Genes in C. elegans

秀丽隐杆线虫突触重塑基因的鉴定

• 批准号: 7230128
• 负责人: DAVID M MILLER
• 金额: $ 16.45万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7230128
• 关键词: Adopted; Affect; Amphibia; Animals; Axon; Axotomy; Biological Metamorphosis; Biological Models; Brain; Caenorhabditis elegans; Candidate Disease Gene; Cells; Class; Data Set; Dendrites; Development; Dorsal; Event; Family; Future; Gene Expression; Genes; Green Fluorescent Proteins; Hippocampus (Brain); In Situ; Individual; Insecta; Larva; Learning; Mammals; Maps; Memory; Microarray Analysis; Modality; Molecular; Motor; Motor Neurons; Nematoda; Nervous system structure; Neurons; Neurotransmitter Receptor; Nuclear Hormone Receptors; Output; Pathway interactions; Pattern; Principal Investigator; Process; Property; Proteins; RNA Interference; Regulation; Reporter; Role; Sensory; Shipping; Ships; Signal Transduction; Specific qualifier value; Staging; Stimulus; Structure; Synapses; Synaptic Vesicles; Technology; Testing; Time; Tissues; Touch sensation; Transcript; Validation; Variant; Vision; base; gamma-Aminobutyric Acid; gene function; in vivo; inhibitor/antagonist; mRNA tagging; member; mutant; neurotransmitter release; postsynaptic; presynaptic; programs; relating to nervous system; research study; response; response to injury; steroid hormone; steroid hormone receptor; transcription factor

DESCRIPTION (provided by applicant): In the nervous system, the pattern of synaptic inputs and outputs defines the direction of information flow. A neuron detects stimuli via elongated processes called dendrites and releases signals from a morphologically distinct class of cytoplasmic extensions called axons. These asymmetric features of neurons are developmentally controlled and fundamentally important to brain function. In the nematode, C. elegans, the DD class of GABA motor neurons undergoes a developmentally regulated reversal of synaptic polarity in which a dendrite switches to become an axon and an axon adopts the properties of a dendrite. Remarkably, DD neuronal processes are not withdrawn to accommodate this change but are remodeled in situ to interconvert pre- and post-synaptic specializations. The implementation of this program is regulated by UNC- 55, a conserved member of the COUP family of nuclear hormone receptor transcription factors. Therefore, we hypothesize that polarity reversal and synaptic remodeling of the DD motor neurons are transcriptionally controlled. We will use new, powerful, cell-specific microarray technology to (1) profile DD motor neurons during the developmental period in which metamorphosis occurs and (2) exploit unc-55 mutants to identify UNC-55 regulated transcripts. A comparison of these data sets should reveal strong candidates for genes that orchestrate polarity reversal and the consequent synaptic remodeling of DD motor neurons. The evident plasticity of vertebrate neuronal asymmetry and the evolutionary conservation of molecules that specify neuronal polarity suggest that our discoveries in a nematode model system will reveal genes with fundamental roles in regulating these events.

描述（由申请人提供）：在神经系统中，突触输入和输出的模式定义了信息流的方向。神经元通过称为树突的细长过程检测刺激，并从形态上不同的一类称为轴突的细胞质延伸释放信号。神经元的这些不对称特征受到发育控制，并且对大脑功能至关重要。在线虫中，DD 类 GABA 运动神经元经历发育调节的突触极性逆转，其中树突转变为轴突，轴突采用树突的特性。值得注意的是，DD 神经元过程并没有被撤回以适应这种变化，而是在原位进行重构以相互转换突触前和突触后的特化。该程序的实施由 UNC-55 调节，UNC-55 是核激素受体转录因子 COUP 家族的保守成员。因此，我们假设 DD 运动神经元的极性反转和突触重塑是转录控制的。我们将使用新的、强大的细胞特异性微阵列技术来 (1) 在发生变态的发育时期分析 DD 运动神经元，以及 (2) 利用 unc-55 突变体来识别 UNC-55 调节的转录本。这些数据集的比较应该揭示出协调极性反转和随后的 DD 运动神经元突触重塑的强有力的候选基因。脊椎动物神经元不对称性的明显可塑性和指定神经元极性的分子的进化保守性表明，我们在线虫模型系统中的发现将揭示在调节这些事件中具有基本作用的基因。