The regulation of male mating behavior in Drosophila

大脑是如何工作的是一个重要而复杂的问题。大脑的众多功能之一是调节行为，如个体之间的社交互动，这反过来又决定着求爱和交配的成功。众所周知，行为是由基因和环境共同决定的，而且这两种影响密切相关。大脑功能也是由荷尔蒙以一种还不太清楚的方式来调节的。这个项目研究了这类荷尔蒙因子及其对果蝇行为的影响，果蝇是一种模式生物，对于果蝇来说，有很好的遗传和分子工具。基因和分子的可及性使这些因素的检查和操作变得更容易。作为该项目的一部分，产生了缺乏假定为编码特定激素样因子的基因的果蝇，并记录了对果蝇行为的影响，以阐明激素样因子与行为之间的关系。该项目还研究了另一个重要问题：这些因子是如何通过血脑屏障的，血脑屏障是包括人类在内的大多数高等生物体中保护大脑的细胞层。这些研究将为血液中循环的荷尔蒙与大脑沟通的方式，以及这一特定的血液与大脑沟通途径如何影响行为提供新的见解。最终，它们将有助于更好地了解大脑是如何工作的。这些研究是在美国最多元化的大学之一进行的，学生人数众多，其中很大一部分来自代表性不足的群体。本科生和研究生都参与了研究，并接受了科学过程中的强化培训。这些研究的总体目标是利用雄性果蝇明确定义的求偶行为作为模式生物，研究复杂行为是如何在分子水平上受到调控的。众所周知，雄性求爱需要特定性别的大脑回路；然而，成功地执行这种行为还需要对这些回路进行调制。循环因子和荷尔蒙是这种调节的重要部分。目前的研究是基于最近的发现，即血脑屏障在这一过程中起着积极的作用。这里描述的研究探索了体液-大脑界面上的特定信号是如何调节求爱的。具体地说，重点是在雄性中优先表达的核受体，作为两种主要昆虫荷尔蒙蜕皮激素和幼虫荷尔蒙之间的联系。条件性遗传操作被用来通过这个蛋白质-激素网络专门在血脑屏障中操纵信号。血脑屏障细胞是荷尔蒙效应发生整合的部位，这一发现有可能在很大程度上扩展对这一组织的欣赏，超越其屏障功能。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

How the brain works is an important and complicated question. One of the many functions of the brain is to regulate behavior, such as social interaction among individuals, which, in turn, determines success in courtship and mating. It is known that behavior is guided by both genes and the environment, and that the influences interact closely. Brain function also is regulated by hormones in ways that are not well understood. This project studies such hormone-like factors and their influence on the behavior of fruit flies, a model organism for which there exist superb genetic and molecular tools. The genetic and molecular accessibility allows for easier examination and manipulation of these factors. As part of this project, flies that lack genes hypothesized to code for specific hormone-like factors are generated, and the effect on the fly's behavior is documented, to elucidate the relation between the hormone-like factors and behavior. The project also examines another important question: How do these factors pass through the blood-brain-barrier, a cell layer that protects the brain in most higher organisms, including humans. These studies will give new insight into the ways by which hormones circulating in blood communicate with the brain, and how this specific route of blood-brain communication influences behavior. Ultimately, they will help to better understand how the brain works. These studies are being performed at one of the most diverse universities in the United States with a large student body, a large fraction of which comes from underrepresented groups. Both undergraduate and graduate students participate in the research and receive intensive training in the scientific process. The overall goal of these studies is to examine how complex behaviors are regulated on a molecular level using the well-defined courtship behavior of male Drosophila as a model organism. It is known that gender-specific brain circuits are required for male courtship; however, successful execution of the behavior also requires modulation of these circuits. Circulating factors and hormones are an important part of this modulation. The present studies are based on the recent discovery that the blood-brain-barrier plays an active role in this process. The studies described here explore how specific signaling at this humoral-brain interface modulates courtship. Specifically, the focus is on a nuclear receptor expressed preferentially in males as a link between the action of the two major insect hormones Ecdysone and Juvenile Hormone. Conditional genetic manipulations are used to manipulate signaling through this protein-hormone network exclusively in the blood-brain-barrier. Findings that blood-brain-barrier cells are a site where integration of hormonal effects occurs have the potential to extend in significant ways appreciation of this tissue beyond its barrier function.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.