Building a Sexually Dimorphic Nervous System

性别差异往往代表着自然界中最戏剧性的种内差异。尽管雄性和雌性拥有相同的基因组和相似的神经系统，但它们在生殖投资方面存在巨大差异，需要不同的形态、生理和行为适应。动物在发育早期就决定了性别，这启动了许多不可逆转的分化事件，影响了基因组和环境如何相互作用，产生性别特有的行为。在整个类群中，这些事件汇聚在一起来调节性二态基因的表达，这指定了性别典型的发育和神经回路功能。然而，在发育过程中起作用的分子程序在很大程度上仍不为人所知。我们的目标是了解遗传上易驯服的醋蝇黑腹果蝇大脑中性二态神经元发育的基因调控网络。鉴于利用醋蝇揭示发育生物学和行为神经科学的基本原理的悠久而卓有成效的历史，它们非常适合于连接这些学科的研究。苍蝇的中央大脑是一个非常复杂的组织，由大约10万个相互连接的神经元组成，形成协调复杂认知和运动功能所需的复杂网络。严格控制的分子程序在一个广泛的发育窗口发挥作用，导致大脑中发现的细胞类型的多样性。单细胞技术的新进展首次使人们能够在整个发育过程中对这种多样性进行全面调查。由于性别在不同发育时期的不同神经元中扮演着不同的角色，我们现在才有办法研究这种复杂结构中性别二态的出现。我们将使用单细胞技术来比较发育中的中央大脑中男性和女性的分子图谱，以了解神经系统中性二型性的潜在机制。这项及时的研究还将产生第一份果蝇中央大脑发育中的单细胞基因表达图谱，这是一个非常有益的资源，将可供研究界使用。更广泛地说，我们的发现将产生一个独特的资源，以研究苍蝇群落及更广泛的神经元电路发育和功能的一般机制，因为许多基本的生化途径和机制在苍蝇和人类之间是保守的。拟议中的实验将描绘出发育中的中枢神经系统中细胞和分子多样性的详细图景。我们的数据将回答一个长期存在的问题：神经元类型如何与生俱来地与性行为相关联？

Sex differences often represent the most dramatic intraspecific variations seen in nature. Although males and females share the same genome and have similar nervous systems, they differ profoundly in reproductive investments and require distinct morphological, physiological, and behavioural adaptations. Animals determine sex early in development, which initiates many irreversible differentiation events that influence how the genome and environment interact to produce sex-specific behaviours. Across taxa, these events converge to regulate sexually dimorphic gene expression, which specifies sex-typical development and neural circuit function. However, the molecular programs that act during development remain largely unknown. We aim to understand the gene regulatory networks underlying sexually dimorphic neuronal development in the brain of the genetically tractable vinegar fly Drosophila melanogaster. Given the long and fruitful history of using vinegar flies to uncover fundamental principles of developmental biology and behavioural neuroscience, they are ideally suited for studies which bridge these disciplines. The fly's central brain is a remarkably complex tissue composed of approximately 100,000 interconnected neurons, forming the intricate networks necessary to coordinate complex cognitive and motor functions. Tightly regulated molecular programs act over a broad developmental window leading to the diversity of cell types found in the brain. New advances in single-cell technologies have enabled, for the first time, a comprehensive survey of this diversity throughout development. As sex plays distinct roles in different neurons at different developmental times, we only now have the means of studying the emergence of sexual dimorphisms within this complex structure. We will use single-cell technologies to compare the molecular profiles of both males and females in the developing central brain to understand the mechanisms underlying sexual dimorphism in the nervous system. This timely study will also generate the first developmental single-cell gene expression atlas of the Drosophila central brain, an immensely beneficial resource that will be available and accessible to the research community. More broadly, our findings will generate a unique resource to investigate general mechanisms underlying the development and functions of neuronal circuits for the fly community and beyond, given that many of the fundamental biochemical pathways and mechanisms are conserved between flies and humans. The proposed experiments will paint a detailed picture of cellular and molecular diversity in a developing central nervous system. Our data will answer the longstanding question: How are neuron types associated with sexual behaviours born and wired?