Mechanisms for Environmental and Genetic Reversal of Gender Biased Behavior

描述(申请人提供)：性与行为之间的关系是一个来自社会、医学界和研究界的长期问题。神经科学研究无可否认地证明，个体的遗传性别对大脑解剖区域和行为都有广泛的影响。然而，一项平行的研究表明，仅根据基因组序列预测表型是不准确的，因此涉及环境影响。我建议使用一种双亲结合的一夫一妻制动物模型来对比遗传和环境对性别偏见行为的影响机制，这种动物模型是一种名为Julidochromis的非洲池鱼。我采用了一种“系统生物学”的方法，定量地整合了来自多个层面的表型数据，包括神经基因表达、激素水平和行为观察。非洲慈鱼为观察自然主义行为提供了一个独特的机会，在这种行为中，性别偏见的行为可以被环境影响或遗传影响逆转。因此，行为表型、激素水平和基因表达谱可以在这三个范例中进行评估：1)传统的性别角色2)环境逆转3)遗传逆转。在传统的性别偏见范式中，雄性更大、更具攻击性和领地，而雌性则提供蛋的照料和巢的维护。在同一物种中，改变社会环境将逆转性别偏见行为，而在密切相关的物种中，性别偏见行为会被遗传背景逆转。多水平表型的协方差分析将确定与性别偏见行为相关的分子模块，而不受性别的影响。范例1将被用作测量和对比两种逆转表型的基线，范例2和范例3中招募的分子模块将被对比，以评估环境和遗传影响的基础机制。性别偏见神经元基因表达的本地化将为这些行为的调节指明神经解剖学位置，从而为建立模型系统奠定基础，在该模型系统中，神经和分子网络协调可塑性和性别角色偏见行为的关系。公共卫生相关性在神经解剖学、神经化学、大脑功能甚至行为层面上，性对大脑的巨大影响是不可否认的。拟议的系统水平研究整合了行为、生理和分子水平的数据，以对比基因和环境影响性别偏见行为的机制，并确定对这些行为的调节重要的神经解剖学位置。我使用一个动物模型(慈嘴鱼)来研究复杂的社会行为，这些行为与人类社会行为中与性别有关的广泛正常差异以及表现出遗传和环境因素的精神疾病直接相关。

DESCRIPTION (provided by applicant): The relationship between sex and behavior is a persistent question from society, as well as the medical and the research communities. Neuroscience research has undeniably demonstrated that the genetic sex of an individual has broad ranging effects on both anatomical brain areas and behaviors. However, a parallel line of research has demonstrated the inaccuracy of predicting phenotype based solely on genome sequence, thus implicating environmental influence. I propose to contrast the mechanisms that underlie genetic and environmental influences on gender biased behaviors using a pair-bonded monogamous animal model of parental care, genus Julidochromis, African cichlid fishes. I take a "systems biology" approach that quantitatively integrates phenotype data from multiple levels including neural gene expression, hormone titers, and behavioral observations. The African Cichlid fishes provide a unique opportunity to observe naturalistic behaviors in which gender-biased behaviors can be reversed by either environmental effects or genetic effects. The behavioral phenotypes, hormone levels, and gene expression profiles can therefore be assessed in these three paradigms 1) conventional gender-role 2) environmental reversal 3) genetic reversal. Within the conventional gender-bias paradigm the males are larger, more aggressive and territorial, while the females provide the egg care and nest maintenance. In this same species, altering the social environment, will reverse gender-biased behaviors, while in a closely related species the gender-biased behaviors are reversed by genetic background. Covariance analysis across multiple levels of phenotype will identify molecular modules that correlate with gender biased behaviors independent of sex. Paradigm 1 will be used as baseline from which to measure and contrast the two reversal phenotypes, and the molecular modules that are recruited in paradigms 2 & 3 will be contrasted in order to evaluate the mechanisms that underlie environmental and genetic influence. The localization of gender-biased neuronal gene expression will indicate neuroanatomical sites for regulation of these behaviors and thus lay the foundation for a model system in which to address the relationship of neural and molecular networks that orchestrate plastic and biased gender-role behavior. PUBLIC HEALTH RELEVANCE The great influence of sex on the brain is undeniable at the level of neuroanatomy, neurochemistry, brain function, and even behavior. The proposed systems level research integrates data from behavioral, physiological and molecular level in order to contrast mechanisms by which genes and the environment influence gender-biased behaviors and identify neuroanatomical sites important for the regulation of these behaviors. I use an animal model (cichlid fish) to study complex social behaviors that are directly relevant to the broad range of normal sex-related differences in human social behaviors as well as psychiatric conditions that show both genetic and environmental components.