A Sexually-dimorphic Brain Module for Sensory Integration

用于感觉统合的性别二态性大脑模块

• 批准号: BB/T001348/1
• 负责人: Stephen Goodwin
• 金额: $ 47.88万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT001348%2F1
• 关键词: Sexually; dimorphic; Brain; Module; Sensory

The complex interplay between a male and female of a species during courtship is one of the most remarkable examples of sexually dimorphic behaviour in the animal kingdom. Upon identifying a suitable partner, Drosophila melanogaster males initiate an elaborate courtship ritual that culminates with copulation. Drosophila females do not actively court males, yet it is her response to the male's advances that determines whether mating will actually occur. These are complex decisions and behaviours controlled by the brain, but working with flies has the advantage of using a vast array of genetic tools that allows us to identify and manipulate relevant neurons in the brain. With these tools we can ask how does the brain differ between the sexes, and how might these differences explain the distinct behaviours of males and females that are critical for reproductive success? Sexually reproducing species exhibit sex differences in social interactions, ostensibly to boost reproductive success and survival of progeny. A core set of sex-typical behavioural displays such as mating, and aggression, although modifiable by experience, are innate in the sense that they can be displayed without prior training. How does an animal's biological sex instruct the behavioural response? Males and females transform sensory input into sexually dimorphic behaviours, suggesting that such behaviours are generated by neural circuits that differ between the sexes These sexual dimorphisms in innate behaviour reflect the action of a sexually differentiated nervous system. Animals determine sex early in their development, and sex determination initiates many irreversible sexual differentiation events that influence how the genome and the environment interact to give rise to sex-specific behaviours. Across taxa, such mechanisms converge to regulate sexually dimorphic gene expression that in turn specifies sex-typical development and neural circuit function.In the fly, sex-specific behaviours are hardwired into the nervous system via the actions of two sex determination transcription factors (TFs), Doublesex (Dsx) and Fruitless (Fru). We have focused our attention on neurons that express these TFs to find anatomical or molecular sex differences in neuronal populations in order to gain an entry point into the neural circuits underlying gender-typical behaviours and identify the neuronal nodes that control component behaviours and behavioural sequencing. Alternative neural circuit wiring configurations have been proposed to generate sexually dimorphic behaviours. Neurons present only in one sex (qualitative sex difference) may either activate or inhibit a sexually dimorphic behaviour in that sex. More commonly in invertebrates and vertebrates, a neuronal population is present in both sexes but presents sex differences (quantitative sex difference) in physiology, neuron number, or connectivity. In such cases, the neurons may regulate the probability of displaying a sexually dimorphic behaviour, or control the display of different sexually dimorphic behaviours in the two sexes (functionally bivalent). We have focused on the role of neurons that express dsx. These dsx+ neurons control male courtship behaviour and aspects of female receptivity. Yet little is known about the specific role of dsx+ neurons in the brain, which are believed to control mating decisions. We identified a group of sexually-dimorphic dsx neurons that are critical to sensory integration in males and females. Importantly, the dimorphism we uncovered can alter connectivity and information flow between males and females, where a dedicated visual pathway processing sex-specific visual cues has evolved in males, but not females.Our goal is to understand how neural circuits in general, and sexually dimorphic neurons in particular, can generate sexually dimorphic behaviours, and how molecular mechanisms and evolutionary constraints shape these behaviours.

一个物种的雄性和雌性在求偶过程中复杂的相互作用是动物王国中性二态行为最显著的例子之一。在确定了一个合适的伴侣后，雄性黑腹果蝇开始了一个精心设计的求爱仪式，最终以交配告终。果蝇雌性并不主动追求雄性，但她对雄性求爱的反应决定了交配是否真的会发生。这些都是由大脑控制的复杂决定和行为，但与苍蝇合作的优势在于使用大量的遗传工具，使我们能够识别和操纵大脑中的相关神经元。有了这些工具，我们可以问两性之间的大脑是如何不同的，以及这些差异如何解释男性和女性对生殖成功至关重要的不同行为？有性繁殖的物种在社会互动中表现出性别差异，表面上是为了提高繁殖成功率和后代的存活率。一套核心的典型性行为表现，如交配和攻击，虽然可以通过经验来改变，但在某种意义上说，它们可以在没有事先训练的情况下表现出来。动物的生理性别如何指导行为反应？男性和女性将感官输入转化为性二态行为，这表明这种行为是由两性之间不同的神经回路产生的。动物在发育早期就决定了性别，性别决定引发了许多不可逆的性分化事件，这些事件影响了基因组和环境如何相互作用，从而产生性别特异性行为。在不同的分类群中，这些机制共同调节性二态基因的表达，从而指定性别典型的发育和神经回路function.In苍蝇，性别特异性行为是硬连线到神经系统通过两个性别决定转录因子（TF），Dougelex（Dsx）和Fruitless（Fru）的行动。我们把注意力集中在表达这些TF的神经元上，以找到神经元群体中的解剖学或分子性别差异，从而获得进入神经回路的切入点，这些神经回路是性别典型行为的基础，并确定控制组件行为和行为序列的神经元节点。已经提出了替代的神经回路布线配置来产生性二态行为。只存在于一种性别中的神经元（质的性别差异）可能激活或抑制该性别的性二态行为。在无脊椎动物和脊椎动物中更常见的是，神经元群体存在于两性中，但在生理学、神经元数量或连接性方面存在性别差异（数量性别差异）。在这种情况下，神经元可以调节显示性二态行为的概率，或者控制两性中不同性二态行为的显示（功能二价）。我们已经集中在表达dsx的神经元的作用。这些dsx+神经元控制雄性的求偶行为和雌性的接受能力。然而，人们对dsx+神经元在大脑中的具体作用知之甚少，人们认为dsx+神经元控制着交配决定。我们发现了一组性别二态dsx神经元，它们对男性和女性的感觉整合至关重要。重要的是，我们发现的二态性可以改变男性和女性之间的连接和信息流，其中处理性别特异性视觉线索的专用视觉通路在男性中进化，而不是女性。我们的目标是了解一般的神经回路，特别是性二态性神经元，如何产生性二态性行为，以及分子机制和进化约束如何塑造这些行为。

项目成果

A sex-specific switch between visual and olfactory inputs underlies adaptive sex differences in behavior.

• DOI: 10.1016/j.cub.2020.12.047
• 发表时间: 2021-03-22
• 期刊: Current biology : CB
• 作者: Nojima T;Rings A;Allen AM;Otto N;Verschut TA;Billeter JC;Neville MC;Goodwin SF
• 通讯作者: Goodwin SF

Generation and characterization of fruitless P1 promoter mutant in Drosophila melanogaster.

• DOI: 10.1080/01677063.2021.1931179
• 发表时间: 2021-09
• 期刊: Journal of neurogenetics
• 影响因子: 1.9
• 作者: Neville MC;Eastwood A;Allen AM;de Haan A;Nojima T;Goodwin SF
• 通讯作者: Goodwin SF