Understanding multi-level impact of male-derived sex peptide on female reproductive behaviours

了解男性性肽对女性生殖行为的多层次影响

• 批准号: BB/Y006364/1
• 负责人: Matthias Soller
• 金额: $ 63.58万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY006364%2F1
• 关键词: Understanding; multi; level; impact; male

Reproductive behaviors and their regulation are most fundamental to all animals. Since they are largely hard-wired into the brain we can learn how behavior is encoded in the brain and shaped by perception and decision-making processes. Understanding how behavior is encoded in the brain is one of the big challenges in biology and requires a behaviorally and genetically tractable model organism. Female reproductive behaviors of the fruit fly Drosophila melanogaster profoundly change after mating leading to refusal to remate and induction of egg laying. Male-derived sex-peptide (SP) is the key molecule inducing these post-mating behaviors, which can last up to one week in the presence of sperm. This very robust behavioral response of Drosophila females to sex-peptide provides the essential prerequisites to map SP responsive neurons and eventually learn how complex behaviors such as mating choice and control of egg laying are encoded in the brain. A key tool to find SP-target neurons is membrane-tethered SP (mSP), that will induce a response when the same neuron that expresses mSP also expresses an SP receptor. Our recent studies showed that there are several distinct neuronal populations that can via exposure to mSP induce refusal to remate and egg laying. Importantly, we could also show that these two post-mating responses can be separated by mSP expression either in the trunk or in the head leading to induction of egg laying or reduction of receptivity, respectively. These exciting findings draw a much more complex picture how SP interferes through multiple sites with female reproductive behaviors to coordinate the post-mating response, yet how this works at a brain systems level remains to be elaborated. We currently have very limited understanding of where SP-target neurons are located in the fly brain. To identify the neuronal circuitry underlying the sex-peptide response, we have used expression of mSP in subsets of neurons of genes involved in the SP-response and the sex-determination pathway. In particular, we subdivided the regulatory region of the broadly expressed SP receptor (SPR) gene into small regulatory fragments expressing only in subsets of neurons. Using this paradigm-shifting approach we have identified small populations of neurons, one that reduces receptivity and induces egg laying, and another one that only induces egg laying upon expression of mSP. Through these experiments we now have worked out, in principle, how to identify all the different populations of SP target neurons. Hence, we now need to identify small regulatory fragments in sex determination genes and SP response pathway genes to identify additional SP target neurons. These experiments will be then be the resource to identify the relevant neurons in the recently become available high-resolution Drosophila brain from the fly connectome project to build the circuitry directing the female post-mating response.With these experiments we will test the hypothesis that SP-target neurons are present at multiple sites in the brain to direct female reproductive behaviors for a coordinated post-mating response. Compared to a previous model arguing for central induction of all PMRs, a modular assembly of individual PMRs holds evolutionary flexibility during speciation and adaptation to diverse habitats, but can maintain basic regulatory principles such as the control of egg laying. We therefore anticipate that the knowledge obtained from our studies will be applicable to a wide range of pest insects pinpointing towards novel strategies for pest management to protect crop and control insect born diseases by interfering with egg laying. In particular, our findings are directly transferable to the close relative Drosophila suzukii, one of the few species able to lay eggs into fruits, which is currently invading Europe including the UK and causing damage in billions to fruit production.

生殖行为及其调控对所有动物来说都是最基本的。由于它们在很大程度上是固定在大脑中的，我们可以了解行为是如何在大脑中编码的，以及如何由感知和决策过程塑造的。理解行为是如何在大脑中编码的是生物学上的一大挑战，需要一个行为和基因上易于处理的模型生物。果蝇交配后雌性繁殖行为发生深刻变化，导致拒绝交配和诱导产卵。雄性性肽(SP)是诱导这些交配后行为的关键分子，在精子存在的情况下，交配后的行为可以持续一周。雌性果蝇对性肽的这种强烈的行为反应为定位SP反应神经元并最终了解交配选择和产卵控制等复杂行为是如何在大脑中编码的提供了必要的先决条件。寻找SP靶神经元的关键工具是膜拴系SP(MSP)，当表达MSP的同一神经元也表达SP受体时，就会产生反应。我们最近的研究表明，有几个不同的神经元群体可以通过暴露于MSP而诱导拒绝交配和产卵。重要的是，我们还可以证明，这两种交配后的反应可以通过MSP在躯干或头部的表达而分开，从而分别导致产卵诱导或感受性降低。这些令人兴奋的发现描绘了一幅更加复杂的图景：SP如何通过多个位置干扰雌性生殖行为，以协调交配后的反应，但这如何在大脑系统水平上发挥作用仍有待详细阐述。我们目前对苍蝇脑中SP靶神经元的位置了解非常有限。为了确定性肽反应背后的神经元回路，我们使用了MSP在参与SP反应和性别决定途径的基因的神经元亚群中的表达。特别是，我们将广泛表达的SP受体(SPR)基因的调节区细分为仅在神经元亚群中表达的小调节片段。使用这种范式转换的方法，我们已经确定了少量神经元，一个降低了感受性并诱导产卵，另一个仅诱导MSP表达产卵。通过这些实验，我们现在已经原则上解决了如何识别所有不同的SP靶神经元群体。因此，我们现在需要识别性别决定基因和SP反应途径基因中的小调控片段，以识别更多的SP靶细胞。这些实验将成为从苍蝇连接组项目中识别最近可用的高分辨率果蝇大脑中的相关神经元的资源，以建立指导雌性交配后反应的电路。通过这些实验，我们将检验这样的假设，即SP靶标神经元存在于大脑中的多个位置，以指导雌性繁殖行为以协调交配后反应。与先前主张对所有PMR进行中心诱导的模型相比，单个PMR的模块化组装在物种形成和适应不同生境的过程中具有进化灵活性，但可以保持基本的调控原则，如控制产卵。因此，我们预计从我们的研究中获得的知识将适用于范围广泛的害虫，以确定害虫管理的新策略，以保护作物并通过干扰产卵来控制昆虫传播的疾病。特别是，我们的发现可以直接转移到近亲铃木果蝇，这是为数不多的能够将卵产下水果的物种之一，目前它正在入侵包括英国在内的欧洲，给水果生产造成数十亿美元的损失。