Dissatisfaction Retained and the Sex Behavior Network

保留的不满和性行为网络

• 批准号: 8208109
• 负责人: MICHAEL B MCKEOWN
• 金额: $ 33.25万
• 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 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8208109
• 关键词: Address; Alleles; Behavior; Behavior Control; Behavioral; Biochemistry; Cell Communication; Cells; Cellular biology; Complex; Courtship; Data; Decision Making; Drosophila genus; Female; Fertility; 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）：了解神经系统发育和安排产生复杂行为的方式是神经科学的一个关键问题，与理解神经系统疾病和对心理健康问题的潜在影响有着实质性的联系。 果蝇的先天行为既复杂又易于通过许多方法进行研究，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。性行为特别容易接受，因为有多种不同的男性和女性行为以及涉及求爱，交配和生育的神经或神经肌肉连接，个体只表达男性或女性的特征。改变男性、女性或两者的性行为的突变已经被分别鉴定和表征。虽然有些功能可能被简单地描述为控制身体或精神，但最近的工作表明，这些基因在多个水平相互作用的调节开关系统中发挥作用。这个网络将被视为一个系统，重点是网络的性质和内部的相互作用。 控制性行为和性别特异性神经发育的行为、神经和调节网络将被关于四个基因进行剖析：保留基因、不满意基因和已知的性别转换基因fruitless和doubledex。每一种都编码一种或多种蛋白质，这些蛋白质作为转录调节因子，与人类中发现的蛋白质具有高度相似性。 与每个基因突变相关的一系列行为异常将被检查，特别强调一个基因的功能和行为网络中其他基因的功能之间的相互作用。将确定每个基因在两种性别中的表达模式和基因之间的重叠。每个基因的靶向敲低将用于将特定行为映射到共表达因子的细胞和仅表达一种因子的细胞。 我们将研究不满意的作用机制，包括它如何改变功能以应对徒劳的活动。关键的测试涉及可能的镇压或激活功能，在一个或两个性别，直接与男性无果蛋白质的相互作用，并激活一个无果引起的不满配体。 公共卫生关系：能够执行复杂功能的神经系统的形成和持续功能，外部输入的整合，决策以及与运动功能的协调对于健康，快乐和富有成效的生活至关重要。将研究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，并且它们在其中起作用的神经元具有上述所有特征。特别强调的是每个基因的活动，它们的相互作用，所涉及的细胞的相互作用，以及可能的激素对行为的贡献，允许潜在的关键连接到人类的类似功能。