Dissatisfaction Retained and the Sex Behavior Network

描述(由申请人提供)：了解神经系统如何发展并安排产生复杂行为是神经科学的一个关键问题，与了解神经系统疾病和对精神健康问题的潜在影响有很大联系。 果蝇的先天行为既复杂，又易于通过遗传学、分子生物学、神经解剖学、生物化学和细胞生物学等方法进行研究。性行为是特别顺从的，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，个体只表现出男性特征集或女性特征集。改变男性、女性或两者的性行为的突变已经被单独识别和表征。虽然有些功能可能被简单地描述为控制身体或精神，但最近的研究表明，这些基因在多个水平上相互作用的调节开关系统中发挥作用。这个网络将作为一个系统来处理，重点放在网络的性质和其中的交互作用上。 控制性行为和性特定神经发育的行为、神经和调控网络将根据四个基因进行剖析：保留、不满意，以及已知的性别转换基因无果和双性。这些蛋白质中的每一个都编码一种或多种蛋白质，这些蛋白质充当转录调节因子，与人类中发现的蛋白质具有高度的相似性。 与每个基因突变相关的一系列行为异常将被研究，特别强调一个基因的功能与行为网络中其他基因功能之间的相互作用。将确定每个基因的两性表达模式以及基因之间的重叠。每个基因的定向敲除将被用来将特定的行为映射到共同表达的细胞因子和只表达一个因子的细胞。 我们将研究不满意的作用机制，包括它在应对无效活动时如何改变功能。关键测试包括一种或两种性别可能的抑制或激活功能，与雄性无果蛋白的直接相互作用，以及由无果诱导的不满配体激活。 与公共健康相关：神经系统的形成和持续功能能够发挥复杂的功能，整合外部输入、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。一个由四个基因组成的神经遗传网络将被研究，这些基因在人类中都有同源基因，它们所在的神经元具有上述所有特征。重点将放在每个基因的活动、它们的相互作用、所涉及的细胞的相互作用以及可能的荷尔蒙对行为的贡献上，从而使潜在的关键连接到人类的类似功能。

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.