Dissatisfaction Retained and the Sex Behavior Network

保留的不满和性行为网络

• 批准号: 7754665
• 负责人: MICHAEL B MCKEOWN
• 金额: $ 33.66万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7754665
• 关键词: Address; Alleles; Behavior; Behavior Control; Behavioral; Biochemistry; Cell Communication; Cells; Cellular biology; Complex; Courtship; Data; Decision Making; Drosophila genus; Female; Fertility; Fibrinogen; Genes; Genetic; Homologous Gene; Hormonal; Human; Individual; Instinct; Life; Ligands; Maps; Mental Health; Mind; Molecular Biology; Motor; Mutation; Nature; Nervous system structure; Neuroanatomy; Neurons; Neurosciences; Overlapping Genes; Partner in relationship; Pattern; Phenotype; Play; Proteins; Published Comment; Repression; Sex Behavior; Switch Genes; System; Testing; Work; base; design; experience; gene function; interest; knock-down; male; mutant; nervous system disorder; neurodevelopment; neuromuscular; protein activation; public health relevance; relating to nervous system; research study; response; sex; trait

DESCRIPTION (provided by applicant): Understanding the way in which a nervous system develops and is arranged to generate complex behaviors is a critical issue for neuroscience, with substantial connections to understanding neurological diseases and potential impact on mental health issues. Innate behaviors of Drosophila are both complex and amenable to study via a number of approaches including genetics, molecular biology, neuroanatomy, biochemistry, and cell biology. Sexual behavior is particularly amenable as there are multiple different male and female behaviors and neural or neuromuscular connections involved in courtship, mating and fertility, with individuals expressing only the male set of traits or the female set. Mutations that alter sexual behavior in males, females or both have been identified and characterized separately. Although some functions might be simplistically described as controlling body or mind, recent work shows that these genes function in a regulatory switch system with interactions at multiple levels. This network will be addressed as a system, with focus on the nature of the network and interactions within it. The behavioral, neural and regulatory network controlling sexual behavior and sex-specific neural development will be dissected with respect to four genes: retained, dissatisfaction, and the known sex- switch genes fruitless and doublesex. Each of these encodes a protein or proteins that act as transcriptional regulators with high similarity to proteins found in humans. The array of behavioral abnormalities associated with mutations in each gene will be examined with special emphasis on interactions between the functions of one gene and functions of others in the behavioral network. Expression patterns in both sexes for each gene and overlaps between genes will be determined. Targeted knock down of each gene will be used to map particular behaviors to cells co- expressing factors and to cells expressing only one factor. The mechanism of action of dissatisfaction, including the way it changes function in response to fruitless activity will be studied. Key tests involve possible repression or activating functions in one or both sexes, direct interaction with male fruitless proteins, and activation by a fruitless induced dissatisfaction ligand. PUBLIC HEALTH RELEVANCE: Formation and continued function of a nervous system capable of complex functions, integration of outside inputs, decision-making, and coordination with motor functions is critical for a healthy, happy and productive life. A neural-genetic network composed of four genes, all of which have homologues in humans, and the neurons in which they act having all the features mentioned above will be studied. Special emphasis will be placed on activities of each of the genes, their interactions, interactions of the cells involved, and possible hormonal contributions to behavior, allowing potential critical connections to similar functions in humans.

描述（由申请人提供）：了解神经系统发展的方式并安排产生复杂的行为是神经科学的关键问题，与理解神经系统疾病和对心理健康问题的潜在影响具有很大的联系。 果蝇的先天行为既复杂又可以通过多种方法进行研究，包括遗传学，分子生物学，神经解剖学，生物化学和细胞生物学。性行为尤其适合，因为有多种不同的男性和女性行为以及求爱和生育的神经或神经肌肉联系，个人只表达男性特征或女性。已经分别确定和表征了改变男性，女性或两者的性行为的突变。尽管某些功能可以简单地描述为控制身体或思想，但最近的工作表明，这些基因在具有多个级别相互作用的调节开关系统中起作用。该网络将作为一个系统来解决，重点是网络的性质和其中的交互。 控制性行为行为和性别特异性神经发育的行为，神经和调节网络将在四个基因上进行剖析：保留，不满意以及已知的性转换基因毫无结果和doublesex。这些中的每一个都编码一种蛋白质或蛋白质，该蛋白质是与人类中发现的蛋白质高相似性的转录调节剂。 将检查与每个基因中突变相关的一系列行为异常，以特别强调一个基因的功能与行为网络中其他基因的功能之间的相互作用。每个基因的性别中的表达模式将确定基因之间的重叠。针对每个基因的靶向敲低将用于将特定行为映射到共同表达因子的细胞和仅表达一个因子的细胞。 不满意的作用机制，包括它对无效活动的响应方式变化的方式。关键测试涉及一个或两个性别中可能的抑制作用或激活功能，与雄性无结果蛋白的直接相互作用以及通过无结果诱导的不满配体激活。 公共卫生相关性：神经系统的形成和持续功能能够复杂功能，外部投入的整合，决策和与运动功能的协调对于健康，幸福和生产力的生活至关重要。一个由四个基因组成的神经遗传网络，所有这些基因在人类中都有同源物，以及它们具有上述所有特征的神经元的作用。特别重点将放在每个基因的活性，它们的相互作用，所涉及的细胞的相互作用以及对行为的可能贡献，从而允许与人类类似功能的潜在关键联系。