Genetic Regulation of Mating Behavior in C. elegan Males

雄性秀丽隐杆线虫交配行为的遗传调控

• 批准号: 7275283
• 负责人: LUIS RENE GARCIA
• 金额: $ 23.73万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275283
• 关键词: Address; Affect; Animals; Arrhythmia; Attenuated; Behavior; Behavior monitoring; Behavioral; Biological Assay; Caenorhabditis elegans; Candidate Disease Gene; Cells; Cloning; Complex; Condition; Contracts; Copulation; Cues; Defect; Genes; Genetic; Goals; Homologous Gene; Human; Ion Channel; Lesion; Long QT Syndrome; Mediating; Molecular; Motor; Motor output; Muscle; Muscle Contraction; Mutation; Nervous system structure; Neurons; Outcome; Partner in relationship; Pathway interactions; Pattern; Penetration; Pharmacology; Potassium Channel; Probability; Procedures; Reflex action; Regulation; Seizures; Sensory; Series; Signal Pathway; Signal Transduction; Site; Specific qualifier value; Standards of Weights and Measures; Stereotyping; Time; Tissues; Vulva; Wild Animals; Work; cell type; heart rhythm; male; positional cloning; promoter; sperm cell; voltage

DESCRIPTION (provided by applicant): The goal of this project is to understand how a step in a complex behavior is genetically specified. This fundamental problem will be addressed by studying C. elegans male mating behavior. During mating, the male executes a series of stereotyped sub-behaviors that result in the insertion of his copulatory spicules into his mate and the subsequent transfer of sperm. Although C. elegans male mating behavior consists of many steps, this project will focus on dissecting how the male inserts his spicules into his mate's vulva. Spicule insertion behavior is a simple reflex; however, the male nervous system and musculature must regulate many factors. The neurons and muscles must compute when to initiate the behavior and monitor if the behavioral outcome was successful. If an insertion attempt fails, the circuitry must re-initiate the behavior. If penetration is successful, the circuitry keeps the spicules inserted while the next behavioral step proceeds. Males display spicule insertion behavior only during mating. However, mutations can be generated that will cause males to display this behavior abnormally in the absence of mating cues. One of these mutations disrupts the C. elegans unc-103 gene. Unc-103 is the C. elegans homolog of the human h-erg-encoded voltage-gated delayed rectifying K+ channel. In humans, HERG channels regulate cardiac rhythm. Mutations in h-erg that reduce ion channel function can increase the probability of spontaneous lethal heart arrhythmias, a condition called long QT syndrome. Spicule insertion behavior requires coordination between different neurons and muscles. Mutations in unc-103 disrupt that regulation and result in spontaneous seizures of male-specific muscles that are used for copulation. To understand how unc-103 is used to regulate behavior, this project will identify where unc-103 is acting in the behavioral circuitry of males. The project will also determine the identities of mutations that affect candidate genes that may act with or in parallel to unc-103 to regulate behavior. Additionally, this project will identify components of activating pathways that must be attenuated by unc-103 during periods between mating.

描述（由申请人提供）：该项目的目标是了解复杂行为的一个步骤是如何通过基因指定的。这个基本问题将通过研究秀丽隐杆线虫雄性交配行为来解决。在交配过程中，雄性会执行一系列刻板的子行为，导致其交配针插入其配偶体内并随后转移精子。尽管线虫雄性交配行为由许多步骤组成，但该项目将重点剖析雄性如何将骨针插入配偶的外阴。骨针插入行为是一种简单的反射；然而，男性神经系统和肌肉组织必须调节许多因素。神经元和肌肉必须计算何时启动行为并监控行为结果是否成功。如果插入尝试失败，电路必须重新启动该行为。如果穿透成功，电路将保持骨针插入，同时进行下一个行为步骤。雄性仅在交配期间表现出骨针插入行为。然而，可能会产生突变，导致雄性在没有交配线索的情况下异常地表现出这种行为。其中一种突变破坏了线虫 unc-103 基因。 Unc-103 是人类 h-erg 编码的电压门控延迟整流 K+ 通道的线虫同源物。在人类中，HERG 通道调节心律。 h-erg 突变会降低离子通道功能，从而增加自发性致命性心律失常的可能性，这种情况称为长 QT 综合征。针状体插入行为需要不同神经元和肌肉之间的协调。 unc-103 的突变破坏了这种调节，导致用于交配的男性特异性肌肉自发癫痫发作。为了了解 unc-103 如何用于调节行为，该项目将确定 unc-103 在男性行为回路中的作用位置。该项目还将确定影响候选基因的突变的身份，这些候​​选基因可能与 unc-103 一起或平行发挥作用来调节行为。此外，该项目将确定在交配期间必须被 unc-103 减弱的激活途径的组成部分。