Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Institute of Zoology, University of Cologne, Köln, Germany.
EMBO J. 2021 Jun 15;40(12):e105763. doi: 10.15252/embj.2020105763. Epub 2021 Apr 13.
The mechanisms controlling wiring of neuronal networks are not completely understood. The stereotypic architecture of the Drosophila mushroom body (MB) offers a unique system to study circuit assembly. The adult medial MB γ-lobe is comprised of a long bundle of axons that wire with specific modulatory and output neurons in a tiled manner, defining five distinct zones. We found that the immunoglobulin superfamily protein Dpr12 is cell-autonomously required in γ-neurons for their developmental regrowth into the distal γ4/5 zones, where both Dpr12 and its interacting protein, DIP-δ, are enriched. DIP-δ functions in a subset of dopaminergic neurons that wire with γ-neurons within the γ4/5 zone. During metamorphosis, these dopaminergic projections arrive to the γ4/5 zone prior to γ-axons, suggesting that γ-axons extend through a prepatterned region. Thus, Dpr12/DIP-δ transneuronal interaction is required for γ4/5 zone formation. Our study sheds light onto molecular and cellular mechanisms underlying circuit formation within subcellular resolution.
神经元网络连接的调控机制尚不完全清楚。果蝇蘑菇体（MB）的典型结构为研究电路组装提供了一个独特的系统。成年果蝇中脑 MB 的γ-叶由一束长长的轴突组成，这些轴突以镶嵌的方式与特定的调制和输出神经元连接，从而定义了五个不同的区域。我们发现，免疫球蛋白超家族蛋白 Dpr12 在γ神经元中自主发挥作用，使其在远端γ4/5 区重新生长，而 Dpr12 和其相互作用蛋白 DIP-δ 都在该区域中富集。DIP-δ 在与γ神经元相连的多巴胺能神经元亚群中发挥作用，位于γ4/5 区。在变态期间，这些多巴胺能投射纤维在γ-轴突之前到达γ4/5 区，这表明γ-轴突通过一个预先形成的区域延伸。因此，Dpr12/DIP-δ 神经元间相互作用对于γ4/5 区的形成是必需的。我们的研究揭示了亚细胞分辨率下的分子和细胞机制在电路形成中的作用。
