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电路的形成及其随后的功能缺陷至关重要。过去四十年的研究表明，胚胎后神经回路的重塑是动物王国中完善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，但神经元回路如何准确地连接在一起，以及在发育过程中回路中同一神经元实体内的功能分区是如何实现的，这是神经科学的一个基本问题，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一过程。它包含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，comme il il故障的gamma4/5区隔化依赖于Dpr12，这是免疫球蛋白超家族的一员，在γ -神经元中细胞自主表达，以及它的相互作用蛋白DIP-δ，这是突触跨位的多巴胺产生神经元亚群所必需的。在发育过程中，神经元将轴突延伸到DIP- δ +神经元占据的Dpr12 / DIP-蛋白富集区域。这表明伽马神经元生长成预图案的叶，其中Dpr12-DIP-delta相互作用是gamma4/5隔室电路结构所必需的。了解神经间通讯在神经回路发育和随后的功能中所起的作用，将为研究发育和疾病期间的神经回路形成和功能提供更广泛的见解。该合作项目旨在了解果蝇蛹发育过程中神经元重塑的分子和细胞机制，以及IgSF分子在神经元间通讯中所起的作用。

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.