Molecular Physiology of the Epitrachael Endocrine System

气管上内分泌系统的分子生理学

• 批准号: 7047892
• 负责人: MICHAEL E ADAMS
• 金额: $ 33.13万
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7047892
• 关键词: Molecular; Physiology; Epitrachael; Endocrine; System; Molecular; Physiology; Epitrachael; Endocrine; System

DESCRIPTION (provided by the applicant): Insect development and behavior are orchestrated by hormonal signaling cascades. We have identified a novel system of epitracheal glands, and associated peptidergic Inka cell, which secretes ecdysis-triggering hormones (ETHs). We will investigate the molecular physiology of this regulatory endocrine system in a genetic model (fruit fly, Drosophila) and a physiological model (moth, Manduca sexta). We previously demonstrated functions for ETHs in regulation of respiratory dynamics and a behavioral sequence associated with ecdysis, and established that ETH is an obligatory chemical signal for survival. The overall objective of this proposal is to provide a better understanding of how gene expression and hormones regulate developmental and behavioral processes. Long-range goals are to provide basic knowledge of chemical signaling processes in organisms applicable to development of therapeutics and management of insect vectors of human diseases. The first objective of the proposal is to define developmental, stage-specific functions for ETHs and to identify neuropeptides controlling their secretion. We will construct conditional promoters of ETH expression to rescue null mutant flies through each stage of development, in order to evaluate the physiological consequences of ETH deficits in later stages of ontogeny. Additional chemical signaling mechanisms, including the neuropeptide corazonin, will be evaluated for their regulation of ecdysis. For the second specific aim, we will examine the steroid regulation of cell-specific expression of ETHs and their release from Inka cells. Finally, our third specific aim will be to identify the nervous system receptor(s) for ETHs and the downstream neuronal targets of ETH action in the CNS. The ecdysis sequence is an excellent model for relating steroid and peptide signaling processes to physiology and behavior. Drosophila offers powerful genetic tools for deletion and conditional expression of key genes involved in these processes, while the moth Manduca offers advantages for endocrinological and physiological manipulations. Use of these models will allow us to pose testable hypotheses at many levels, and to mobilize genetic and cellular approaches appropriate to each objective. The simplicity of the epitracheal endocrine system, composed of glands containing only 1-4 cells, provides an excellent model for examination of endocrine function at the cellular, developmental and molecular levels. Since ecdysis is crucial for successful development of insects and other arthropods, understanding the regulatory mechanisms which underlie these precisely timed and synchronized processes should allow in the future for more sophisticated approaches to the study of basic physiology and behavior.

描述（由申请人提供）：昆虫的发育和行为是由荷尔蒙信号级联编排的。我们已经确定了一个新型的表情腺体系统，以及相关的肽GINKA细胞，该细胞分泌递归触发激素（ETHS）。我们将在遗传模型（果蝇，果蝇）和生理模型（Moth，Manduca Sexta）中研究该调节性内分泌系统的分子生理。我们先前在调节呼吸动力学和与递归相关的行为序列方面的功能证明了ETH的功能，并确定ETH是生存的强制性化学信号。该提案的总体目的是更好地了解基因表达和激素如何调节发育和行为过程。远程目标是提供适用于治疗剂和人类疾病昆虫媒介的生物中化学信号过程的基本知识。该提案的第一个目的是定义ETH的发育，特定于阶段的功能，并确定控制其分泌的神经肽。我们将构建ETH表达的条件启动子，以挽救在发育的每个阶段，以挽救无空突变体蝇，以评估个体发育阶段的伦理缺陷的生理后果。将评估包括神经肽corazonin在内的其他化学信号传导机制，以调节其递归。对于第二个特定目的，我们将检查ETH细胞特异性表达的类固醇调节及其从Inka细胞中释放。最后，我们的第三个具体目的是确定CNS中ETH和ETH作用的下游神经元靶标的神经系统受体。递归序列是将类固醇和肽信号传导过程与生理学和行为相关联的绝佳模型。果蝇为这些过程中涉及的关键基因的删除和有条件表达提供了强大的遗传工具，而蛾甘达（Moth Manduca）为内分泌和生理操纵提供了优势。这些模型的使用将使我们能够在许多层面上提出可检验的假设，并动员适合每个目标的遗传和细胞方法。由仅包含1-4个细胞的腺体组成的上聚集内分泌系统的简单性为检查细胞，发育和分子水平的内分泌功能提供了极好的模型。由于对昆虫和其他节肢动物的成功发展至关重要，因此了解这些精确定时和同步过程的调节机制应在将来允许使用更复杂的基本生理学和行为研究的方法。