Elucidating How Neuropeptides Communicate Chemosensory Information During Developmental Decision Making

项目总结/摘要 我们理解神经系统内的交流的框架传统上集中在 神经递质为基础的突触传递，从而忽略了神经肽及其 同源受体作为调节元件。越来越清楚的是，神经肽调节 通过调节神经元之间和组织之间的通信来调节重要的神经过程。 因此，神经肽与广泛的神经障碍有关，包括 神经退行性疾病，如阿尔茨海默病和帕金森病。然而，精确的分子 解释神经肽如何参与神经传递的机制还没有被很好地理解。的 该提案的首要目标是使用线虫秀丽隐杆线虫作为模式生物， 进一步了解神经肽如何在密集连接的神经系统中传递信息， 系统在这个提议中，我计划描绘一种基于神经肽的信号传导机制， 化学感受信息，以便做出重要的发育决定。具体来说， 这项提案将研究神经肽如何参与dauer退出决定，这是一个不可逆的过程。 发展决策，其中C。已经进入抗应激滞育状态的线虫 （称为dauer）选择退出该状态并作为后期幼虫返回其生殖生命周期 蠕虫该提案的目的1旨在广泛识别和表征神经肽基因， 退出决定的决定Aim 2采用单神经元方法，并专注于特定的化学感受 神经元的重要性dauer出口：ASJ神经元。在这个目标中，我将确定ASJ依赖于哪种神经肽 以调解多尔的退出决定。最后，在目标3中，我研究了神经肽本身是如何 调节响应适当的外部刺激，通过使用报告技术深入研究， ASJ神经元中一种特殊的神经肽基因的调节被证明对dauer退出是重要的。 总的来说，所有这三个目标将描绘一个更清晰的画面，神经肽如何作为一个桥梁， 化学感受输入和下游发育程序在生物体，如C。优雅

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.