Elucidating How Neuropeptides Communicate Chemosensory Information During Developmental Decision Making

阐明神经肽在发育决策过程中如何传递化学感应信息

• 批准号: 10534152
• 负责人: Mark G Zhang
• 金额: $ 4.77万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10534152
• 关键词: Ablation; Afferent Neurons; Alzheimer' s Disease; Biological Assay; Caenorhabditis elegans; Communication; Crowding; Cues; Data Set; Decision Making; Development; Diapause; Elements; Environment; Food; Genes; Genetic; Genetic Epistasis; Genetic Transcription; Goals; Knock-out; Lasers; Life Cycle Stages; Mediating; Microfluidics; Modality; Molecular; Nematoda; Nervous System; Neurodegenerative Disorders; Neurologic Process; Neuromodulator; Neurons; Neuropeptide Gene; Neuropeptides; Neurotransmitters; Organism; Parkinson Disease; Pathway interactions; Peptides; Phenotype; Pheromone; Process; Regulation; Reporter; Resistance; Role; Sensory; Signal Pathway; Signal Transduction; Starvation; Stimulus; Stress; Synaptic Transmission; Technology; Testing; Tissues; Transcriptional Regulation; chronic pain; environmental flux; experimental study; improved; loss of function; model organism; mutant; nervous system disorder; neurotransmission; novel; overexpression; programs; receptor; reproductive; response; sensory input; transcriptome sequencing; transmission process

Project Summary / Abstract Our framework of understanding communication within the nervous system has traditionally focused on neurotransmitter-based synaptic transmission, thereby leaving out the importance of neuropeptides and their cognate receptors as modulatory elements. It is becoming increasingly clear that neuropeptides regulate important neurological processes by mediating communication between neurons and across tissues. Accordingly, neuropeptides have been implicated a broad array of neurological disorders including neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease. However, the precise molecular mechanisms that explain how neuropeptides participate in neurotransmission are not well understood. The overarching goal of this proposal is to use the roundworm Caenorhabditis elegans as a model organism to further our understanding of how neuropeptides communicate information within a densely connected nervous system. In this proposal, I plan to delineate a neuropeptide-based signaling mechanism that transmits chemosensory information in order to make an important developmental decision. Specifically, this proposal will study how neuropeptides participate in the dauer exit decision, which is an irreversible developmental decision in which C. elegans that have previously entered the stress-resistant diapause state (termed dauer) choose to exit from that state and return to their reproductive life cycle as late stage larval worms. Aim 1 of this proposal seeks to broadly identify and characterize neuropeptide genes that are essential for the dauer exit decision. Aim 2 takes a single neuron approach and focuses on a specific chemosensory neuron essential for dauer exit: the ASJ neuron. In this aim, I will identify which neuropeptide(s) ASJ relies on in order to mediate the dauer exit decision. Finally, in Aim 3, I examine how neuropeptides themselves are regulated in response to appropriate external stimuli by using reporter technology to in-depth study the regulation of one particular neuropeptide gene in the ASJ neuron demonstrated to be important for dauer exit. Collectively, all three aims will portray a clearer picture of how neuropeptides serve as a bridge between chemosensory inputs and downstream developmental programs in an organism such as C. elegans.

项目概要/摘要 我们理解神经系统内沟通的框架传统上集中于 基于神经递质的突触传递，从而忽略了神经肽及其重要性 作为调节元件的同源受体越来越清楚，神经肽的调节作用。 通过介导神经元之间和跨组织的通信来实现重要的神经过程。 因此，神经肽与多种神经系统疾病有关，包括 然而，阿尔茨海默病和帕金森病等神经退行性疾病的精确分子。 解释神经肽如何参与神经传递的机制尚不清楚。 该提案的总体目标是使用线虫秀丽隐杆线虫作为模式生物 进一步加深我们对神经肽如何在紧密连接的神经系统内传递信息的理解 在这个提案中，我计划描述一种基于神经肽的信号传导机制。 具体来说，这是为了做出重要的发育决定。 该提案将研究神经肽如何参与 dauer 退出决策，这是一个不可逆转的过程 先前进入抗应激滞育状态的线虫的发育决定 （称为 dauer）选择退出该状态并作为晚期幼虫返回其生殖生命周期 该提案的目标 1 旨在广泛识别和表征重要的神经肽基因。 对于 dauer 退出决策，目标 2 采用单神经元方法并专注于特定的化学感应。 dauer 退出所必需的神经元：ASJ 神经元 在这个目标中，我将确定 ASJ 依赖哪种神经肽。 为了调解 dauer 退出决定，最后，在目标 3 中，我研究了神经肽本身的情况。 通过使用报告技术深入研究对适当的外部刺激进行调节 ASJ 神经元中一种特定神经肽基因的调节被证明对于 dauer 退出很重要。 总的来说，这三个目标将更清晰地描绘神经肽如何充当两者之间的桥梁 线虫等生物体的化学感应输入和下游发育程序。