DISSERTATION RESEARCH: The role of Maternal Hormones in Programming Offspring Aggression

母亲对当前环境的荷尔蒙反应可能会导致其发育中的后代发生永久性变化，可能决定这些后代在未来环境中的生存或死亡。在竞争性更强的环境中繁殖的雌性往往会在产前将更多的睾丸激素传递给后代，这会永久地使后代更具攻击性。这种母体效应可能有助于后代适应竞争环境，但目前还不清楚母体来源的睾酮如何永久影响后代的行为。如果不知道它是如何发生的，就很难描述这种母性效应的遗传性，以及它如何适应更大的进化框架。这项研究是第一个测试分子机制，如基因表达和控制的变化，介导母体睾酮对鸟类后代攻击性的影响，其中这种母体效应是最好的研究。这项研究将采取一种新的方法，探索来自几种大脑通路的攻击相关基因的差异。这项研究的结果将有助于澄清是什么导致了攻击行为的长期变化，以及为什么动物行为存在差异。研究人员还将对本科生进行实验室方法和生物信息学方面的培训。此外，这项研究还与美国各地的鸣禽饲养者一起开展了一个公民科学项目，以探索影响鸟类繁殖的因素。具体来说，研究人员将通过实验确定表观遗传机制（即，DNA甲基化）是鸣禽母体激素对后代攻击性编程的基础。鸟类是母亲效应的极好模型，因为它们的幼崽在卵中外部发育，雌性将大量的睾丸激素分配给它们的蛋黄。研究人员将给斑胸草雀的蛋注射对照载体或睾丸激素，并测量攻击性和竞争性行为（即，生长率和乞讨率）。在这些后代的一个子集中，研究人员将测试表观遗传编程的证据。攻击行为是在许多相互作用的基因（即，类固醇受体、组胺、多巴胺、生长抑素、精氨酸催产素等）。因此，研究人员将使用RNA-seq和methyl-seq分析来探索两个社会相关大脑区域（端脑和间脑）中攻击相关基因的mRNA表达和位点特异性甲基化模式的全基因组差异。这项研究将极大地扩展我们对不同基因网络如何在大脑区域相互作用以表达攻击性的知识，并将提供第一个鸟类DNA甲基化组。本项目产生的所有数据将在适当的电子储存库中存档。

A mother's hormonal response to her current environment can cause permanent changes in her developing offspring, potentially determining whether those offspring live or die in their future environment. Females breeding in more competitive environments tend to transfer more testosterone to their offspring prenatally, which permanently makes offspring more aggressive. This maternal effect may help offspring adapt to competitive environments, yet it is still unclear how maternally derived testosterone permanently impacts offspring behavior. Without knowing how it happens, it is difficult to characterize the heritability of this maternal effect and how it fits into larger evolutionary frameworks. This research is among the first to test if molecular mechanisms, such as changes in gene expression and control, mediate the effects of maternal testosterone on offspring aggression using birds, in which this maternal effect is best studied. This research will take a novel approach by exploring differences in aggression-related genes from several brain pathways. The results of this research will help clarify what contributes to long-lasting variation in aggressive behaviors and why differences in animal behaviors exist. The researchers will also train undergraduate students in laboratory methods and bioinformatics. Additionally, this research has lent itself to a citizen science project with songbird breeders throughout the United States to explore factors influencing avian reproduction. Specifically, the researchers will experimentally determine if an epigenetic mechanism (i.e., DNA methylation) underlies the programming of offspring aggression by maternal hormones in songbirds. Birds are excellent models for maternal effects because their young develop externally in eggs and females allocate substantial amounts of testosterone to their egg yolks. The researchers will inject zebra finch eggs with a control vehicle or testosterone and measure aggressive and competitive behaviors (i.e., growth rate and begging rate) in the resulting offspring. In a subset of these offspring, the researchers will test for evidence of epigenetic programming. Aggressive behaviors are initiated across many interacting genes (i.e., steroid receptors, histamine, dopamine, somatostatin, arginine vasotocin, etc.). Thus, the researchers will use RNA-seq and methyl-seq analyses to explore genome-wide differences in mRNA expression and site-specific methylation patterns of aggression-related genes in two socially-relevant brain regions, the telencephalon and diencephalon. This research will greatly expand our knowledge of how different gene networks interact across brain regions to express aggression and will provide one of the first avian DNA methylomes. All data generated in this project will be archived in appropriate electronic repositories.