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

轴突和树突的靶向对于回路形成及其随后的正常功能是至关重要的。过去四十年的研究表明，神经回路的胚胎后重塑是改善动物界功能回路的关键策略。重塑可以被设想为神经回路发育的最后一步，但是神经回路如何精确地连接在一起，以及在发育过程中如何在回路中的同一神经元实体内实现功能区室化，这是神经科学中的一个基本问题，仍然只是部分理解。果蝇蘑菇体γ叶提供了一个独特的系统来研究这些过程。它具有五个不同的亚细胞区室，由不同功能意义的神经元亚型的局部神经支配所定义。在我们的初步研究中，我们能够证明，正常的gamma 4/5区室化依赖于Dpr 12，免疫球蛋白超家族的一个成员，在gamma-神经元中细胞自主表达，以及其相互作用蛋白DIP-δ，这是在突触中所需的跨位点的多巴胺产生神经元的子集。在发育过程中，γ-神经元将其轴突延伸到Dpr 12/ DIP-蛋白富集区域，该区域被DIP-δ +神经元占据。这表明γ-神经元生长成预图案化的叶，其中Dpr 12-DIP-δ相互作用是γ 4/5隔室电路结构所需的。了解神经间通信在电路发展和电路的后续功能中所起的作用，将为电路在发展和疾病过程中的形成和功能提供更广泛的见解。拟议的合作项目旨在了解神经元重塑的分子和细胞机制，以及IgSF分子在果蝇蛹发育过程中MB电路改造过程中在神经元间通信中发挥的作用。

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.