Department of Biomedical Sciences, Cornell University Ithaca, NY, USA.
Front Neural Circuits. 2011 Aug 23;5:9. doi: 10.3389/fncir.2011.00009. eCollection 2011.
Olfactory sensory neurons (OSNs) are thought to use activity-dependent and independent mechanisms to regulate the expression of axon guidance genes. However, defining the molecular mechanisms that underlie activity-dependent OSN guidance has remained elusive. Only a handful of genes have been identified whose expression is regulated by activity. Interestingly, all of these genes have been shown to play a role in OSN axon guidance, underscoring the importance of identifying other genes regulated by activity. Furthermore, studies suggest that more than one downstream mechanism regulates target gene expression. Thus, both the number of genes regulated by activity and how many total mechanisms control this expression are not well understood. Here we identify delta protocadherin 10 (pcdh10) as a gene regulated by activity. Delta protocadherins are members of the cadherin superfamily, and pcdh10 is known to be important for axon guidance during development. We show pcdh10 is expressed in the nasal epithelium and olfactory bulb in patterns consistent with providing guidance information to OSNs. We use naris occlusion, genetic manipulations, and pharmacological assays to show pcdh10 can be regulated by activity, consistent with activation via the cyclic nucleotide-gated channel. Transgenic analysis confirms a potential role for pcdh10 in OSN axon guidance.
嗅觉感觉神经元（OSN）被认为使用依赖活动和独立的机制来调节轴突导向基因的表达。然而，定义活动依赖性 OSN 导向的分子机制仍然难以捉摸。只有少数几个基因的表达被确定受到活动的调节。有趣的是，所有这些基因都被证明在 OSN 轴突导向中发挥作用，这强调了确定其他受活动调节的基因的重要性。此外，研究表明，不止一种下游机制调节靶基因的表达。因此，不仅受活动调节的基因数量，而且控制这种表达的总机制数量都没有得到很好的理解。在这里，我们确定 delta 原钙粘蛋白 10（pcdh10）为受活动调节的基因。Delta 原钙粘蛋白是钙粘蛋白超家族的成员，pcdh10 已知在发育过程中对轴突导向很重要。我们表明，pcdh10 在鼻上皮和嗅球中的表达模式与为 OSN 提供导向信息一致。我们使用鼻腔阻塞、遗传操作和药理学测定来表明 pcdh10 可以受到活动的调节，这与通过环核苷酸门控通道的激活一致。转基因分析证实了 pcdh10 在 OSN 轴突导向中的潜在作用。
