期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：12
DOI：10.1073/pnas.2111283119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The adult
Drosophila mushroom body (MB) is one of the most extensively studied neural circuits. However, how its circuit organization is established during development is unclear. In this study, we provide an initial characterization of the assembly process of the extrinsic neurons (dopaminergic neurons and MB output neurons) that target the vertical MB lobes. We probe the cellular mechanisms guiding the neurite targeting of these extrinsic neurons and demonstrate that Semaphorin 1a is required in several MB output neurons for their dendritic innervations to three specific MB lobe zones. Our study reveals several intriguing molecular and cellular principles governing assembly of the MB circuit.
The
Drosophila mushroom body (MB) is composed of parallel axonal fibers from intrinsic Kenyon cells (KCs). The parallel fibers are bundled into five MB lobes innervated by extrinsic neurons, including dopaminergic neurons (DANs) and MB output neurons (MBONs) that project axons or dendrites to the MB lobes, respectively. Each DAN and MBON innervates specific regions in the lobes and collectively subdivides them into 15 zones. How such modular circuit architecture is established remains unknown. Here, we followed the development of the DANs and MBONs targeting the vertical lobes of the adult MB. We found that these extrinsic neurons innervate the lobes sequentially and their neurite arborizations in the MB lobe zones are independent of each other. Ablation of DAN axons or MBON dendrites in a zone had a minimal effect on other extrinsic neurites in the same or neighboring zones, suggesting that these neurons do not use tiling mechanisms to establish zonal borders. In contrast, KC axons are necessary for the development of extrinsic neurites. Dendrites of some vertical lobe-innervating MBONs were redirected to specific zones in the horizontal lobes when their normal target lobes were missing, indicating a hierarchical organization of guidance signals for the MBON dendrites. We show that Semaphorin 1a is required in MBONs to innervate three specific MB zones, and overexpression of
semaphorin 1a is sufficient to redirect DAN dendrites to these zones. Our study provides an initial characterization of the cellular and molecular mechanisms underlying the assembly process of MB extrinsic neurons.
关键词：enDrosophilamushroom bodydopaminergic neuronsmushroom body output neuronsSemaphorin 1a
