Williams Eric O, Xiao Yuanyuan, Sickles Heather M, Shafer Paul, Yona Golan, Yang Jean Y H, Lin David M
Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA.
BMC Dev Biol. 2007 May 16;7:48. doi: 10.1186/1471-213X-7-48.
In the mouse olfactory system, the role of the olfactory bulb in guiding olfactory sensory neuron (OSN) axons to their targets is poorly understood. What cell types within the bulb are necessary for targeting is unknown. What genes are important for this process is also unknown. Although projection neurons are not required, other cell-types within the external plexiform and glomerular layers also form synapses with OSNs. We hypothesized that these cells are important for targeting, and express spatially differentially expressed guidance cues that act to guide OSN axons within the bulb.
We used laser microdissection and microarray analysis to find genes that are differentially expressed along the dorsal-ventral, medial-lateral, and anterior-posterior axes of the bulb. The expression patterns of these genes divide the bulb into previously unrecognized subdomains. Interestingly, some genes are expressed in both the medial and lateral bulb, showing for the first time the existence of symmetric expression along this axis. We use a regeneration paradigm to show that several of these genes are altered in expression in response to deafferentation, consistent with the interpretation that they are expressed in cells that interact with OSNs.
We demonstrate that the nascent external plexiform and glomerular layers of the bulb can be divided into multiple domains based on the expression of these genes, several of which are known to function in axon guidance, synaptogenesis, and angiogenesis. These genes represent candidate guidance cues that may act to guide OSN axons within the bulb during targeting.
在小鼠嗅觉系统中,嗅球在引导嗅觉感觉神经元(OSN)轴突至其靶标的作用仍知之甚少。嗅球内哪些细胞类型对靶向是必需的尚不清楚。哪些基因对这一过程很重要也不清楚。尽管投射神经元并非必需,但外丛状层和肾小球层内的其他细胞类型也与OSN形成突触。我们推测这些细胞对靶向很重要,并表达在空间上差异表达的导向线索,这些线索在嗅球内引导OSN轴突。
我们使用激光显微切割和微阵列分析来寻找在嗅球背腹、内外侧和前后轴上差异表达的基因。这些基因的表达模式将嗅球划分为以前未被识别的亚区域。有趣的是,一些基因在内侧和外侧嗅球均有表达,首次表明沿此轴存在对称表达。我们使用再生范式表明,其中一些基因的表达在去传入神经后发生改变,这与它们在与OSN相互作用的细胞中表达的解释一致。
我们证明,基于这些基因的表达,嗅球新生的外丛状层和肾小球层可分为多个区域,其中一些基因已知在轴突导向、突触形成和血管生成中起作用。这些基因代表了可能在靶向过程中引导嗅球内OSN轴突的候选导向线索。