Robo2 is required for establishment of a precise glomerular map in the zebrafish olfactory system
Robo2 is required for establishment of a precise glomerular map in the zebrafish olfactory system
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DOI：
10.1242/dev.01698
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发表时间：
2005-03-01
期刊：
影响因子：
4.6
通讯作者：
Yoshihara, Y
中科院分区：
文献类型：
--
作者：
Miyasaka, N;Sato, Y;Yoshihara, Y
表达特定气味受体的嗅觉感觉神经元 (OSN) 将其轴突投射到特定的肾小球，在嗅球 (OB) 中创建地形气味图。 OSN 轴突寻路至精确目标的机制尚不完全清楚。在这里，我们证明了 Robo2/Slit 信号传导功能可将新生嗅轴突引导至斑马鱼的 OB 原基。 robo2 在嗅觉轴突寻路的初始阶段短暂地在嗅觉基板中表达。在行突变体中，迷途(ast)，早期生长的嗅轴突向腹内侧或后侧错误走行，并且经常穿透到间脑而不到达OB原基。四种斑马鱼 Slit 同源物在嗅觉轴突轨迹附近的区域表达，这与它们作为 Robo2 排斥配体的作用一致。转基因鱼中普遍存在的 Slit2 错误表达掩盖内源性 Slit 梯度，导致类似于 ast 表型的后部寻路错误。我们还发现 OB 中肾小球的空间排列在 ast 成虫中受到干扰，这表明初始嗅觉轴突支架在确定肾小球地形图方面发挥着重要作用。这些数据为 Robo2/Slit 信号在斑马鱼嗅觉神经回路建立中提供了功能证据。
Olfactory sensory neurons (OSNs) expressing a given odorant receptor project their axons to specific glomeruli, creating a topographic odor map in the olfactory bulb (OB). The mechanisms underlying axonal pathfinding of OSNs to their precise targets are not fully understood. Here, we demonstrate that Robo2/Slit signaling functions to guide nascent olfactory axons to the OB primordium in zebrafish. robo2 is transiently expressed in the olfactory placode during the initial phase of olfactory axon pathfinding. In the roW mutant, astray (ast), early growing olfactory axons misroute ventromedially or posteriorly, and often penetrate into the diencephalon without reaching the OB primordium. Four zebrafish Slit homologs are expressed in regions adjacent to the olfactory axon trajectory, consistent with their role as repulsive ligands for Robo2. Masking of endogenous Slit gradients by ubiquitous misexpression of Slit2 in transgenic fish causes posterior pathfinding errors that resemble the ast phenotype. We also found that the spatial arrangement of glomeruli in OB is perturbed in ast adults, suggesting an essential role for the initial olfactory axon scaffold in determining a topographic glomerular map. These data provide functional evidence for Robo2/Slit signaling in the establishment of olfactory neural circuitry in zebrafish.