Dock and Pak regulate olfactory axon pathfinding in Drosophila
Dock and Pak regulate olfactory axon pathfinding in Drosophila
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DOI：
10.1242/dev.00356
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发表时间：
2003-04-01
期刊：
影响因子：
4.6
通讯作者：
Hing, H
中科院分区：
文献类型：
--
作者：
Ang, LH;Kim, J;Hing, H
表达特定气味受体（Or）基因的嗅觉轴突在大脑中空间不变的肾小球上的会聚是发育神经生物学中精确轴突靶向的最引人注目的例子之一。嗅觉神经轴突寻找其靶点的细胞和分子机制还知之甚少。我们在这里报告的SH 2/SH 3衔接码头和丝氨酸/苏氨酸激酶Pak是必要的嗅觉轴突的精确指导。使用抗体定位，马赛克分析和细胞类型特异性救援，我们观察到，码头和帕克在嗅觉轴突中表达和功能自主嗅觉神经元，以调节嗅觉地图的精确布线。在整个突变体和小的多细胞克隆的突变体表型的详细分析表明，码头和帕克不控制嗅觉神经元（ON）的分化，但具体调节轴突轨迹的多个方面，以引导他们的同源肾小球。结构/功能研究表明，Dock和Pak形成了一条信号通路，介导了发育中的触角叶（AL）中嗅觉轴突对引导线索的反应。因此，我们的研究结果确定了一个中央信号模块，用于ON项目，其同源肾小球。
The convergence of olfactory axons expressing particular odorant receptor (Or) genes on spatially invariant glomeruli in the brain is one of the most dramatic examples of precise axon targeting in developmental neurobiology. The cellular and molecular mechanisms by which olfactory axons; pathfind to their targets are poorly understood. We report here that the SH2/SH3 adapter Dock and the serine/threonine kinase Pak are necessary for the precise guidance of olfactory axons. Using antibody localization, mosaic analyses and cell-type specific rescue, we observed that Dock and Pak are expressed in olfactory axons and function autonomously in olfactory neurons to regulate the precise wiring of the olfactory map. Detailed analyses of the mutant phenotypes in whole mutants and in small multicellular clones indicate that Dock and Pak do not control olfactory neuron (ON) differentiation, but specifically regulate multiple aspects of axon trajectories to guide them to their cognate glomeruli. Structure/function studies show that Dock and Pak form a signaling pathway that mediates the response of olfactory axons to guidance cues in the developing antennal lobe (AL). Our findings therefore identify a central signaling module that is used by ONs to project to their cognate glomeruli.