Emergence and maintenance of neuronal function and behavior in the fly: from embryonic scenes through larval and adult stages to dysfunctions – EmFly

Long-term maintenance of neuronal function is critical to preserve an animal’s behaviour throughout its life. How is this achieved during developmental stages and in pathological conditions? I will study the mechanisms of this maintenance in the nervous system of the fruit fly, Drosophila melanogaster. Specifically, I will determine how neuronal activity emerges in embryos. This will provide clues as to how neural activity is genetically modulated and maintained within behavioural circuits beyond the embryonic stage and how disruptions in this process may contribute to neurodegenerative disorders. To this end, I will pursue three aims:
1. How does neuronal activity emerge in embryo and drive motor development?
2. How do neurons transit from larva to adult fly while preserving similar functions?
3. How do early adaptive strategies of neurons influence neurodegenerative disorders?
Neurons are post-mitotic and long-lived cells. They undergo perpetual plasticity at all organizational levels in response to experience and environment, securing their ability to function and adapt throughout life. Here I will study the maintenance of such ability at different levels of the organism. As an holometabolous insect, Drosophila provides a powerful model, since: (i) exquisite genetic tools are available to record and manipulate neurons in this organism, (ii) its brain is less complex and much smaller than that of mammals permitting optical access, and (iii) it expresses a large array of well-studied and quantifiable behaviours. Interestingly, Drosophila undergoes complete metamorphosis from larva to adult stages, coupled with a drastic neuroplasticity process that is required to ensure that similar behaviours can be performed in both stages. Studying in Drosophila the patterns of activity and gene expression within the (a) embryo, (b) larval and (c) adult post-mitotic neurons that modulate behaviour across stages, in normal and pathological conditions, will vastly increase our understanding of the molecular and developmental bases of neuronal function.