Netrin/DCC signaling guides olfactory sensory axons to their correct location in the olfactory bulb.
Netrin/DCC signaling guides olfactory sensory axons to their correct location in the olfactory bulb.
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DOI：
10.1523/jneurosci.4442-11.2012
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发表时间：
2012-03-28
期刊：
影响因子：
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通讯作者：
Raper JA
中科院分区：
文献类型：
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作者：
Lakhina V;Marcaccio CL;Shao X;Lush ME;Jain RA;Fujimoto E;Bonkowsky JL;Granato M;Raper JA
嗅觉感觉神经元表达特定的嗅觉受体投射到球茎内特定的可复制位置。组织这种精确投射模式的轴突引导线索才刚刚开始被识别。为了帮助鉴定和表征它们，我们生成了一个转基因斑马鱼品系，OR111-7:IRES:Gal4，其中一小部分嗅觉感觉神经元被标记。大多数表达OR111-7转基因的感觉神经元投射到球茎内的特定位置，即中央区原肾小球，而少数投射到LG1原肾小球。抑制netrin/DCC信号会干扰OR111-7表达轴突进入嗅球的能力，并改变它们在嗅球内的终止模式。netrin受体DCC在嗅觉感觉神经元中轴突发育时表达，netrin1a在嗅球最内侧边缘附近表达，netrin1b在嗅球腹侧区域表达。netrin/DCC信号组分的缺失导致一些表达OR111-7的感觉轴突在离开嗅坑后向后漫游，远离球茎内的netrin表达区。表达OR111-7的轴突进入球茎后，其靶向中心区域的精确度低于正常水平，并从网蛋白表达区向外扩散。这些寻路错误可以通过在DCC变形胚胎中表达OR111-7转基因的神经元中重新表达DCC来纠正。这些发现表明，网络是唯一已知的嗅觉感觉神经元的引诱物，首先将表达OR111-7的轴突吸引到球茎中，然后进入位于腹内侧的中央区原肾小球。
Olfactory sensory neurons expressing particular olfactory receptors project to specific reproducible locations within the bulb. The axonal guidance cues that organize this precise projection pattern are only beginning to be identified. To aid in their identification and characterization, we generated a transgenic zebrafish line, OR111-7:IRES:Gal4, in which a small subset of olfactory sensory neurons is labeled. Most sensory neurons expressing the OR111-7 transgene project to a specific location within the bulb, the central zone protoglomerulus, while a smaller number project to the LG1 protoglomerulus. Inhibiting netrin/DCC signaling perturbs the ability of OR111-7 expressing axons to enter the olfactory bulb and alters their patterns of termination within the bulb. The netrin receptor DCC is expressed in olfactory sensory neurons around the time that they elaborate their axons, netrin1a is expressed near the medial-most margin of the olfactory bulb, and netrin1b is expressed within the ventral region of the bulb. Loss of netrin/DCC signaling components causes some OR111-7 expressing sensory axons to wander posteriorly after exiting the olfactory pit, away from netrin expressing areas in the bulb. OR111-7 expressing axons that enter the bulb target the central zone less precisely than normal, spreading away from netrin expressing regions. These pathfinding errors can be corrected by the re-expression of DCC within OR111-7 transgene expressing neurons in DCC morphant embryos. These findings implicate netrins as the only known attractants for olfactory sensory neurons, first drawing OR111-7 expressing axons into the bulb and then into the ventromedially positioned central zone protoglomerulus.