Molecular Physiology of the Epitrachael Endocrine System

气管上内分泌系统的分子生理学

• 批准号: 8052747
• 负责人: MICHAEL E ADAMS
• 金额: $ 39.32万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8052747
• 关键词: Ablation; Address; Adolescent; Adult; Aedes; Alternative Splicing; Animal Model; Animals; Arthropods; Automobile Driving; Baculoviruses; Behavior; Behavioral; Bombyx; Bombyx mori; Calcium; Calcium Oscillations; Cells; Communities; Complex; Culicidae; DNA Transposable Elements; Data; Development; Developmental Process; Diuretics; Drosophila genus; Economic Inflation; Electrophysiology (science); Embryonic Development; Endocrine system; Etiology; Event; Excision; Exons; Failure; Funding; G-Protein-Coupled Receptors; Gene Deletion; Gene Expression; Gene Silencing; Genes; Genetic; Genome; Health; Hormonal; Hormone Receptor; Hormones; Human; Image; In Vitro; Insecta; Investigation; Ion Channel; Kinins; Knock-out; Lead; Ligands; Light; Liquid substance; Mediating; Modeling; Molecular; Molecular Analysis; Molecular Biology; Molting; Moths; Neuraxis; Neurons; Neuropeptide Gene; Neuropeptides; Neurosecretory Systems; Organism; Orthologous Gene; Outcome; Pattern; Peptide Signal Sequences; Peptides; Phenotype; Physiology; Population; Process; Program Development; Public Health; RNA; RNA Interference; Reagent; Regulation; Respiratory System; Respiratory physiology; Rhodopsin; Role; Schedule; Series; Signal Transduction; Signaling Molecule; Staging; System; Temperature; Testing; Ticks; Time; Work; Yellow Fever; base; bursicon; fly; human disease; in vivo; insight; katacalcin; life history; mutant; neuropeptide F; overexpression; peptide hormone; programs; receptor; receptor expression; research study; respiratory; steroid hormone; synergism; tool; vector

DESCRIPTION (provided by applicant): The neuroendocrine system programs development through release of steroid and peptide hormones at critical times during the life history of the organism. We are investigating the neuroendocrine basis of an innate behavioral sequence in model insects. At the end of each developmental stage, release of peptide ecdysis triggering hormones (ETH) programs a sequence of respiratory and behavioral events culminating in cuticle shedding and transition to the next stage. The scheduling of these events occurs via a downstream peptide signaling cascade in the central nervous system (CNS). The long-term objectives of this proposal are to gain new insights into how this signaling cascade coordinates the timing and proper sequence of events necessary for survival of the organism. The first objective of the proposal is to elucidate functions for ETHR-A and ETHR-B neurons in the ecdysis sequence by RNA silencing or overexpression of each receptor subtype to distinguish their functions. The second specific aim will define precise functions of peptidergic signaling in initiation and scheduling of the ecdysis behavioral sequence. We will use molecular tools to activate or ablate specific peptidergic ensembles to test their necessary roles in the ecdysis sequence in Drosophila, Aedes, and Bombyx. The third specific aim is to elucidate how the ETH-activated central peptide signaling cascade mediates respiratory inflation. In particular, the critical roles of peptide kinin signaling will be examined using cell-specific ablation, RNA gene silencing and cell-specific activation with light or temperature-activated ion channels. We will use several strategies for hypothesis-testing of the roles of specific peptidergic ensembles in ETH-induced behaviors. These are: 1) correlation of cellular activity and peptide action with behaviors by imaging and electrophysiology, 2) driving ensembles using overexpression of ETH receptor subtypes and cell-specific activation with appropriate ligands (ETH) or channel rhodopsins, and 3) removal of neurons and/or genes by cell-specific ablation and neuropeptide-specific RNA silencing. The ecdysis sequence is a series of clearly defined steps under the control of peptide hormones and transmitters. It provides a favorable model for molecular analysis of a complex developmental process involving respiratory dynamics and behaviors. It is likely that scheduling of these events by peptidergic signaling cascades in the CNS is of general significance and relevance to all animals. Understanding the regulatory mechanisms, which underlie these precisely timed developmental processes will offer new insights into how behavior is controlled by the neuroendocrine system, and may lead to a better understanding of normal and pathological states in humans. Results of these studies also may provide basic new information about vector-borne human diseases involving mosquitoes, flies, ticks, and other arthropods. PUBLIC HEALTH RELEVANCE The ecdysis sequence is a series of clearly defined steps under the control of peptide hormones and transmitters. It provides a favorable model for molecular analysis of a complex developmental process involving respiratory dynamics and behaviors. It is likely that scheduling of these events by peptidergic signaling cascades in the CNS is of general significance and relevance to all animals. Understanding the regulatory mechanisms, which underlie these precisely timed developmental processes, will offer new insights into how behavior is controlled by the neuroendocrine system, and may lead to a better understanding of normal and pathological states in humans. Results of these studies also may provide basic new information about vector-borne human diseases involving mosquitoes, flies, ticks, and other arthropods.

描述（由申请人提供）：神经内分泌系统计划通过在生物体生活史上在关键时期释放类固醇和肽激素来开发。我们正在研究模型昆虫先天行为序列的神经内分泌基础。在每个发育阶段结束时，肽递归的释放触发激素（ETH）程序程序一系列呼吸和行为事件的序列最终导致角质层脱落和过渡到下一阶段。这些事件的调度是通过中枢神经系统（CNS）中的下游肽信号传导级联发生的。该提案的长期目标是获得新的见解，以了解该信号级联如何协调生物生存所需的时间和适当的事件顺序。该提案的第一个目的是通过RNA沉默或过度表达每个受体亚型以区分其功能，以阐明递归序列中ETHR-A和ETHR-B神经元的功能。第二个特定目的将定义肽基信号在启动和调度行为序列中的精确功能。我们将使用分子工具激活或消融特定的肽Gemembles，以测试其在果蝇，艾德斯和Bombyx的递归序列中的必要作用。第三个具体目的是阐明伦理激活的中央肽信号传导如何介导呼吸道膨胀。特别是，将使用细胞特异性消融，RNA基因沉默和通过光或温度激活的离子通道来检查肽Kinin信号传导的临界作用。我们将使用几种策略来假设特定肽吉尼斯在伦理诱导的行为中的作用。这些是：1）通过成像和电生理学与行为的相关性，2）使用ETH受体亚型的过度表达和通过细胞特异性ablectific Ablectific ryna rneific inna rence ryafe and ofe eTH受体亚型和细胞特异性激活进行驱动集合。递归序列是在肽激素和发射器的控制下的一系列明确定义的步骤。它为涉及呼吸动力学和行为的复杂发育过程的分子分析提供了一个有利的模型。 CNS中的肽吉尼信号传导级联对这些事件的调度很可能与所有动物具有一般意义和相关性。理解这些精确定时发展过程的基础的监管机制将为神经内分泌系统如何控制行为的新见解，并可能会更好地理解人类正常和病理状态。这些研究的结果还可以提供有关涉及蚊子，苍蝇，tick虫和其他节肢动物的媒介传播人类疾病的基本新信息。公共卫生相关性递归序列是一系列在肽激素和发射器控制下的一系列明确定义的步骤。它为涉及呼吸动力学和行为的复杂发育过程的分子分析提供了一个有利的模型。 CNS中的肽吉尼信号传导级联对这些事件的调度很可能与所有动物具有一般意义和相关性。了解这些精确定时发展过程的监管机制将提供有关神经内分泌系统如何控制行为的新见解，并可能会更好地了解人类正常和病理状态。这些研究的结果还可以提供有关涉及蚊子，苍蝇，tick虫和其他节肢动物的媒介传播人类疾病的基本新信息。