Molecular Physiology of the Epitrachael Endocrine System

气管上内分泌系统的分子生理学

基本信息

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
项目类别：
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

项目摘要

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）：神经内分泌系统通过在生物体生命史的关键时刻释放类固醇和肽激素来规划发育。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，肽蜕皮触发激素（ETH）的释放会编程一系列呼吸和行为事件，最终导致角质层脱落并过渡到下一阶段。这些事件的调度是通过中枢神经系统 (CNS) 中的下游肽信号级联发生的。该提案的长期目标是获得关于信号级联如何协调有机体生存所需事件的时间和正确顺序的新见解。该提案的第一个目标是通过 RNA 沉默或每种受体亚型的过度表达来区分其功能，从而阐明蜕皮序列中 ETHR-A 和 ETHR-B 神经元的功能。第二个具体目标将定义肽能信号在蜕皮行为序列的启动和调度中的精确功能。我们将使用分子工具激活或消除特定的肽能群，以测试它们在果蝇、伊蚊和家蚕蜕皮序列中的必要作用。第三个具体目标是阐明 ETH 激活的中枢肽信号级联如何介导呼吸充气。特别是，将使用细胞特异性消融、RNA 基因沉默以及光或温度激活离子通道的细胞特异性激活来检查肽激肽信号传导的关键作用。我们将使用多种策略来假设检验特定肽能群在 ETH 诱导行为中的作用。这些是：1) 通过成像和电生理学将细胞活性和肽作用与行为相关联，2) 使用 ETH 受体亚型的过度表达和用适当的配体 (ETH) 或通道视紫红质进行细胞特异性激活来驱动整体，以及 3) 去除神经元和/或基因通过细胞特异性消融和神经肽特异性RNA沉默。蜕皮序列是在肽激素和递质的控制下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有利的模型。中枢神经系统中肽能信号级联对这些事件的调度可能具有普遍意义并且与所有动物相关。了解这些精确定时的发育过程背后的调节机制将为了解神经内分泌系统如何控制行为提供新的见解，并可能有助于更好地理解人类的正常和病理状态。这些研究的结果还可能提供有关涉及蚊子、苍蝇、蜱虫和其他节肢动物的媒介传播人类疾病的基本新信息。公共卫生相关性蜕皮序列是在肽激素和递质的控制下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有利的模型。中枢神经系统中肽能信号级联对这些事件的调度可能具有普遍意义并且与所有动物相关。了解这些精确定时的发育过程背后的调节机制，将为了解神经内分泌系统如何控制行为提供新的见解，并可能有助于更好地理解人类的正常和病理状态。这些研究的结果还可能提供有关涉及蚊子、苍蝇、蜱虫和其他节肢动物的媒介传播人类疾病的基本新信息。