Mechanisms of pheromone signal transduction in C. elegans

描述（由申请人提供）：信息素既可作为短期嗅觉线索，发出危险或配偶存在的信号，也可作为长期线索，通过调节神经内分泌轴介导发育和生理变化。很少有人知道的机制，信息素信号转导调节神经激素信号在哺乳动物中，虽然这种信号的失调可能会导致发育和行为障碍。嗅觉信号转导机制在生物体中高度保守，神经传递机制也是如此，这表明在模式生物中研究这些过程可以为高等生物中的相关过程提供见解。 In C.在线虫中，dauer信息素通过调节激素信号调节进入交替dauer发育阶段，并提供了一个极好的模型系统，用于探索信息素信号如何被识别和转导以控制关键的发育决策。近年来，在中国竹荪中发现了两种结构上相似的子囊苷类化合物，它们是构成dauer信息素的重要成分。elegans，C.在其他模式生物中，其突变体在信息素介导的激素信号调节中有缺陷的秀丽线虫仍然难以捉摸。这个建议的目标是确定额外的受体所需的信息素信号转导，并表征神经元间信息素信号传递所需的基因。这项工作将有助于我们了解信息素调节关键行为和发育决策的途径，以及这些途径的功能障碍如何导致发育受损，行为障碍和肥胖。建议的具体目标是：1。C3信号转导所需神经元和受体的鉴定。 2.细胞间信息素信号通路的鉴定。 信息素是一种分泌的分子，在同一物种的动物之间传递即时和长期的信号。为了全面了解人类的气味，以及气味如何影响发育和行为，有必要彻底了解检测和传递信息素信号的机制。这项工作将导致更好地了解大脑如何处理化学信号，以及化学感觉系统功能障碍如何导致发育受损，行为障碍和肥胖。

DESCRIPTION (provided by applicant): Pheromones act as both short-term olfactory cues that signal danger or the presence of mates, as well as long-term cues, which mediate changes in development and physiology via modulation of the neuroendocrine axis. Little is known about the mechanisms by which pheromone signals are transduced to modulate neurohormonal signaling in mammals, although dysregulation of this signaling can result in developmental and behavioral disorders. Olfactory signal transduction mechanisms are highly conserved across organisms, as are mechanisms of neuronal transmission, indicating that studying these processes in model organisms may provide insights into related processes in higher organisms. In C. elegans, the dauer pheromone regulates entry into the alternate dauer developmental stage via regulation of hormonal signaling, and provides an excellent model system in which to explore how pheromone signals are recognized and transduced to govern a critical developmental decision. The recent identification of both the structurally related ascarosides comprising dauer pheromone in C. elegans, and the first two pheromone receptors in C. elegans, whose mutants are defective in pheromone-mediated regulation of hormonal signaling, remains elusive in other model organisms. The goal of this proposal is to identify additional receptors required for pheromone signal transduction, and to characterize a gene required for inter-neuronal pheromone signal transmission. This work will contribute to our understanding of the pathways by which pheromones regulate critical behavioral and developmental decisions, and how dysfunction of these pathways can lead to impaired development, behavioral disorders, and obesity. The proposed specific aims are: 1. Identification of the neurons and receptors required for C3 ascaroside signal transduction ascaroside. 2. Identification of intercellular pheromone signaling pathways. PUBLIC HEALTH RELEVANCE: Pheromones are secreted molecules that communicate immediate and long-term signals among animals of the same species. For a complete understanding of how humans smell, and how odors affect development and behavior, a thorough understanding of the mechanisms of detecting and relaying pheromonal signals is necessary. This work will lead to a better understanding of how the brain processes chemical signals, and how dysfunction of the chemosensory system leads to impaired development, behavioral disorders, and obesity.