The role of IgSF protein Dpr12 in the developmental assembly of mushroom body circuits in Drosophila melanogaster

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Targeting of axons and dendrites is critical for circuit formation and its subsequent comme il faut functionality. Studies in the last four decades have shown that post-embryonic remodeling of neural circuits is a key strategy to refine functional circuits across animal kingdoms. Remodeling can be envisioned as the last step in the development of neural circuits but how exactly neuronal circuits wire together and how functional compartmentalization within the same neuronal entity in the circuit during development is achieved is a fundamental problem in neuroscience that is still only partially understood. The Drosophila mushroom body γ-lobe offers a unique system to study such processes. It harbors five distinct subcellular compartments defined by localized innervations of neuronal sub-types of different functional significance. In our preliminary studies we were able to demonstrate that the comme il faut gamma4/5 compartmentalization depends on Dpr12, a member of the immunoglobulin superfamily that is cell-autonomously expressed in gamma-neurons, as well as on its interacting protein DIP-δ that is required in synaptically across sited subsets of dopamine producing neurons. During development the gamma-neurons extend their axons into Dpr12 / DIP- protein enriched regions that are preoccupied by DIP-delta+ neurons. This indicates that gamma-neurons grow into pre-patterned lobes where Dpr12-DIP-delta interaction is required for gamma4/5 compartment circuit architecture. Understanding the role interneural communication plays in circuit development and in the subsequent function of the circuit will provide broader insights into circuit formation and function during development and disease. The proposed collaborative project aims at understanding molecular and cellular mechanisms underlying neuronal remodeling and which role IgSF molecules play in interneuronal communication during the reformation of MB circuits during pupal development in Drosophila melanogaster.