Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.
Department of Zoology and Neurobiology, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Curr Biol. 2019 May 6;29(9):1445-1459.e3. doi: 10.1016/j.cub.2019.03.050. Epub 2019 Apr 18.
Building sensory dendritic arbors requires branching, growth, spacing, and substrate support. The conserved L1CAM family of cell-adhesion molecules generates neuronal isoforms to regulate neurite development in various aspects. However, whether non-neuronal isoforms participate in any of these aspects is unclear. In Drosophila, the L1CAM homolog Neuroglian (Nrg) is expressed as two isoforms: the neuronal isoform Nrg180 on dendritic surfaces of dendritic arborization (da) neurons and the non-neuronal isoform Nrg167 in epidermis innervated by dendrites. We found that epidermal Nrg167 encircles dendrites by interactions with dendritic Nrg180 to support dendrite growth, stabilization, and enclosure inside epidermis. Interestingly, whereas Nrg180 forms homophilic interactions to facilitate axonal bundling, heteroneuronal dendrites in the same innervating field avoid bundling through unknown mechanisms to maintain individual dendritic patterns. Here, we show that both epidermal Nrg167 depletion and neuronal Nrg180 overexpression can cause dendrite bundling, with genetic analyses suggesting that Nrg167-Nrg180 interactions antagonize Nrg180-Nrg180 homophilic interaction to prevent dendrite bundling. Furthermore, internalization of Nrg180 also participates in resolving dendrite bundling, as overexpression of endocytosis-defective Nrg180 and compromising endocytosis in neurons both exacerbated dendrite-bundling defects. Together, our study highlights the functional significance of substrate-derived Nrg167 in conferring dendrite stability, positioning, and avoidance.
构建感觉树突树需要分支、生长、间隔和基底支持。保守的细胞粘附分子 L1CAM 家族产生神经元同工型，以在各个方面调节神经突发育。然而，非神经元同工型是否参与其中任何一个方面尚不清楚。在果蝇中，L1CAM 同源物 Neuroglian (Nrg) 表达为两种同工型：树突分支 (da) 神经元树突表面的神经元同工型 Nrg180 和由树突支配的表皮中的非神经元同工型 Nrg167。我们发现表皮 Nrg167 通过与树突 Nrg180 的相互作用环绕树突，以支持树突生长、稳定和在表皮内包绕。有趣的是，虽然 Nrg180 形成同亲性相互作用以促进轴突束集，但同一支配区域中的异神经元树突通过未知机制避免束集，以维持单个树突模式。在这里，我们表明表皮 Nrg167 的耗竭和神经元 Nrg180 的过表达都可以导致树突束集，遗传分析表明 Nrg167-Nrg180 相互作用拮抗 Nrg180-Nrg180 同亲性相互作用以防止树突束集。此外，Nrg180 的内化也参与了解决树突束集，因为内陷缺陷型 Nrg180 的过表达和神经元内陷的破坏都加剧了树突束集缺陷。总之，我们的研究强调了来源于基底的 Nrg167 在赋予树突稳定性、定位和避免方面的功能意义。
