Stephen Goodwin - Neuroscience - 'Building a Sexually Dimorphic Nervous System'

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 sexspecific 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?