Different levels of the Tripartite motif protein, Anomalies in sensory axon patterning (Asap), regulate distinct axonal projections of Drosophila sensory neurons

Different levels of the Tripartite motif protein, Anomalies in sensory axon patterning (Asap), regulate distinct axonal projections of Drosophila sensory neurons
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DOI:
10.1073/pnas.1109843108
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发表时间:
2011-11-29
影响因子:
11.1
通讯作者:
Emoto, Kazuo
Emoto, Kazuo
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Morikawa, Rei K.;Kanamori, Takahiro;Emoto, Kazuo

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感觉神经元的轴突投射模式通常受到环境信号的调节,但是不同的感觉传入如何在相同的环境中建立不同的投射仍然是未知的。果蝇IV类树突树枝状(C4da)感觉神经元项目亚型特定的轴突分支在腹神经索,我们表明,三分基序蛋白,异常感觉轴突图案(Asap)是一个关键的决定因素的轴突投射模式的不同C4da神经元。Asap在具有同侧和对侧轴突投射的C4da神经元中高度表达,但在仅具有同侧投射的神经元中Asap水平较低。Asap突变导致对侧投射的特定损失,而Asap过表达诱导C4da神经元的异位对侧投射。我们还通过生化和遗传分析表明,Asap调节Netrin信号传导,至少部分通过将Netrin受体Frazzled连接到下游效应物皮科。在没有Asap的情况下,腹神经索内的感觉传入连接被破坏,导致特定的幼虫行为缺陷。这些结果表明,不同水平的Asap通过调节Netrin信号传导来确定C4da神经元轴突投射的不同模式,并且Asap介导的轴突投射对于功能性感觉回路的组装是至关重要的。
The axonal projection pattern of sensory neurons typically is regulated by environmental signals, but how different sensory afferents can establish distinct projections in the same environment remains largely unknown. Drosophila class IV dendrite arborization (C4da) sensory neurons project subtype-specific axonal branches in the ventral nerve cord, and we show that the Tripartite motif protein, Anomalies in sensory axon patterning (Asap) is a critical determinant of the axonal projection patterns of different C4da neurons. Asap is highly expressed in C4da neurons with both ipsilateral and contralateral axonal projections, but the Asap level is low in neurons that have only ipsilateral projections. Mutations in asap cause a specific loss of contralateral projections, whereas overexpression of Asap induces ectopic contralateral projections in C4da neurons. We also show by biochemical and genetic analysis that Asap regulates Netrin signaling, at least in part by linking the Netrin receptor Frazzled to the downstream effector Pico. In the absence of Asap, the sensory afferent connectivity within the ventral nerve cord is disrupted, resulting in specific larval behavioral deficits. These results indicate that different levels of Asap determine distinct patterns of axonal projections of C4da neurons by modulating Netrin signaling and that the Asap-mediated axonal projection is critical for assembly of a functional sensory circuit.