Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
Neuron. 2011 Dec 8;72(5):734-47. doi: 10.1016/j.neuron.2011.09.026.
During assembly of the Drosophila olfactory circuit, projection neuron (PN) dendrites prepattern the developing antennal lobe before the arrival of axons from their presynaptic partners, the adult olfactory receptor neurons (ORNs). We previously found that levels of transmembrane Semaphorin-1a, which acts as a receptor, instruct PN dendrite targeting along the dorsolateral-ventromedial axis. Here we show that two secreted semaphorins, Sema-2a and Sema-2b, provide spatial cues for PN dendrite targeting. Sema-2a and Sema-2b proteins are distributed in gradients opposing the Sema-1a protein gradient, and Sema-1a binds to Sema-2a-expressing cells. In Sema-2a and Sema-2b double mutants, PN dendrites that normally target dorsolaterally in the antennal lobe mistarget ventromedially, phenocopying cell-autonomous Sema-1a removal from these PNs. Cell ablation, cell-specific knockdown, and rescue experiments indicate that secreted semaphorins from degenerating larval ORN axons direct dendrite targeting. Thus, a degenerating brain structure instructs the wiring of a developing circuit through the repulsive action of secreted semaphorins.
在果蝇嗅觉回路的组装过程中，投射神经元（PN）的树突在来自其突触前伴侣——成年嗅觉受体神经元（ORN）的轴突到达之前，预先规划了发育中的触角叶的位置。我们之前发现，作为受体的跨膜信号素-1a 的水平指示 PN 树突沿着背-腹侧-腹侧轴的靶向。在这里，我们表明两种分泌的信号素，Sema-2a 和 Sema-2b，为 PN 树突的靶向提供空间线索。Sema-2a 和 Sema-2b 蛋白呈梯度分布，与 Sema-1a 蛋白梯度相反，并且 Sema-1a 与表达 Sema-2a 的细胞结合。在 Sema-2a 和 Sema-2b 双突变体中，原本在触角叶中背-侧靶向的 PN 树突错误地向腹-侧靶向，这模拟了这些 PN 中细胞自主去除 Sema-1a 的表型。细胞消融、细胞特异性敲低和拯救实验表明，来自退化的幼虫 ORN 轴突的分泌信号素指导树突的靶向。因此，退化的大脑结构通过分泌信号素的排斥作用来指导发育中回路的布线。
