The regulation of gut-brain communication during Caenorhabditis elegans dauer development

秀丽隐杆线虫发育过程中肠-脑通讯的调节

• 批准号: 10152625
• 负责人: Mengyi Cao
• 金额: $ 6.86万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152625
• 关键词: Acids; Anabolism; Animal Behavior; Animal Model; Animals; Brain; Caenorhabditis elegans; Communication; Data; Decision Making; Development; Diapause; Disease; Environment; Fluorescence; Gastrointestinal tract structure; Gene Expression Profile; Genes; Genetic Recombination; Genetic Transcription; Goals; Growth Factor; Hormones; Immunity; Individual; Insulin; Intestines; Irritable Bowel Syndrome; Knowledge; Life; Ligands; Literature; Mental Health; Metabolism; Modeling; Molecular; Molecular Genetics; Nematoda; Nervous system structure; Neuroendocrine Cell; Organ; Parkinson Disease; Pathway interactions; Physiology; Process; Publishing; Regulation; Regulator Genes; Regulatory Pathway; Reporter; Reporting; Research; Role; Signal Pathway; Signal Transduction; Site; Stress; System; Testing; Tissues; Transforming Growth Factor beta; Translations; Whole Organism; assay development; base; food shortage; gut-brain axis; improved; overpopulation; physical conditioning; promoter; receptor; response; spatiotemporal; tool; transcription factor S-II

Project Summary The communication among different tissues (or organs), such as the gut-brain axis, is crucial in regulating animal physiology and developmental decisions. The nematode Caenorhabditis elegans enters a non-feeding, developmentally arrested dauer stage to cope with the harsh environments, such as food shortage and over- population. The dauer decision is regulated by the multiple pathways (insulin, growth factor, and hormone), involving the nervous system, XXX neuroendocrine cells, and intestine. Previous research has established C. elegans as a model organism to study stress-responsive development, but tissue-specific regulation of dauer development remains unclear. In particular, little is known about how nervous system coordinates with the intestine to integrate the signaling pathways and make a whole-organism dauer decision. The proposed aims focus on providing a systematic study of how different tissues communicate through multiple signaling pathways and coordinately regulate the dauer decision using molecular genetics tools recently developed in the sponsor lab. To achieve this goal, Aim 1 will focus on investigating the general roles of each tissue during dauer development and build models for the regulatory network; Aim 2 will focus on temporal participation of each tissue and each pathway in dauer decision initiation and execution, further developing precise circuits of dauer regulation. Altogether, the proposed aims will expand the current knowledge of molecular mechanisms underlying developmental timing of commitment to diapause in response to environmental stress. Using C. elegans dauer decision as a model, the proposed project will contribute to better understanding of the inter-tissue coordination, particularly in brain-gut communication, during the developmental decision making process.

项目概要 不同组织（或器官）之间的通讯，例如肠-脑轴，对于调节至关重要 动物生理学和发育决定。线虫秀丽隐杆线虫进入非摄食状态， 发育停滞的多尔阶段，以应对恶劣的环境，例如食物短缺和过度 人口。多尔决定受到多种途径（胰岛素、生长因子和激素）的调节， 涉及神经系统、XXX神经内分泌细胞和肠道。先前的研究已确立 线虫作为模型生物来研究应激反应发育，但组织特异性调节 dauer 的发展仍不清楚。特别是，人们对神经系统如何协调的知之甚少。 肠道整合信号通路并做出整个生物体的决策。拟议的 目标侧重于提供不同组织如何通过多种方式进行交流的系统研究 信号通路并使用分子遗传学工具协调调节 dauer 决策 最近在赞助者实验室开发。为了实现这一目标，目标 1 将重点调查一般情况 每个组织在 dauer 发育过程中的作用并建立监管网络模型；目标 2 将重点关注 每个组织和每个路径在 Dauer 决策启动和执行中的时间参与，进一步 开发精确的 dauer 调节电路。总而言之，拟议的目标将扩大当前的 了解滞育反应的发育时间的分子机制 环境压力。使用秀丽隐杆线虫 dauer 决策作为模型，拟议的项目将有助于 更好地理解组织间的协调，特别是在脑肠沟通方面 发展决策过程。

项目成果

Effects of ASD-associated daf-18/PTEN missense variants on C. elegans dauer development.

ASD 相关的 daf-18/PTEN 错义变异对秀丽隐杆线虫 dauer 发育的影响。

• DOI: 10.17912/micropub.biology.000177
• 发表时间: 2019
• 期刊: microPublication biology
• 作者: González-Cavazos,Carolina;Cao,Mengyi;Wong,Wan-Rong;Chai,Cynthia;Sternberg,Paul
• 通讯作者: Sternberg,Paul