Transcription factors specify the fate and connectivity of developing neurons. We investigate how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs) by regulating the expression of cell-surface proteins. Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains, and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions. These include canonical cell adhesion molecules and proteins previously not associated with wiring, such as Piezo, whose mechanosensitive ion channel activity is dispensable for its function in PN dendrite targeting. Comprehensive genetic analyses revealed that Acj6 employs unique sets of cell-surface proteins in different PN types for dendrite targeting. Combined expression of Acj6 wiring executors rescued acj6 mutant phenotypes with higher efficacy and breadth than expression of individual executors. Thus, Acj6 controls wiring specificity of different neuron types by specifying distinct combinatorial expression of cell-surface executors.

转录因子决定了发育中神经元的命运和连接性。我们研究谱系特异性转录因子 Acj6 如何通过调节细胞表面蛋白的表达来控制果蝇嗅觉投射神经元 (PN) 的精确树突靶向。对完整发育中的大脑中野生型和acj6突变 PN 进行定量细胞表面蛋白质组分析，并通过蛋白质组信息遗传筛选鉴定出执行 Acj6 调节的接线决策的 PN 表面蛋白。其中包括以前与布线无关的经典细胞粘附分子和蛋白质，例如 Piezo，其机械敏感离子通道活性对于其在 PN 树突靶向中的功能来说是可有可无的。综合遗传分析表明，Acj6 采用不同 PN 类型中独特的细胞表面蛋白组来靶向树突。Acj6 连线执行子的组合表达比单个执行子的表达具有更高的功效和广度，从而挽救了acj6突变表型。因此，Acj6 通过指定细胞表面执行器的不同组合表达来控制不同神经元类型的接线特异性。