A Molecular Basis on Generation and Regenaration of the Olfactory Sensory Map

人们普遍认为，每个嗅觉感觉神经元（OSN）仅以互斥的单等位方式表达一个气味受体（OR）基因。OR基因探针原位杂交（ISH）表明，嗅上皮（OE）可以分为四个地形不同的区域，表达给定OR基因的osn随机分布在一个区域内。各种脊椎动物的OR基因在系统发育上可分为I类和II类。第一类OR基因，首先在鱼类中发现，后来在两栖动物中发现，被认为具有水溶性气味配体。II类嗅觉障碍是陆地特有的，占哺乳动物嗅觉障碍的很大一部分，并在小鼠嗅觉系统中进行了详细的研究。最近，我们发现每个II类OR基因的表达区域都是特异性的，并且在OE中以重叠的方式排列。相比之下，I类or的表达模式和投射部位尚不完全清楚。在本研究中，我们系统地分析了小鼠I类OR基因（42个亚家族），以阐明OE中的表达谱及其OSNs在OB中的投射位点。ISH显示，大多数I类OR基因（36个亚家族）在OE的背内侧区（1区）表达。此外，在1区内表达I类基因的osn的分布似乎没有显著差异。这些结果表明，OE的1区与非1区之间存在明显的边界。已知一些I类or对脂肪酸、醛类和醇类具有配体特异性。我们的ISH分析显示，在1区表达I类or的osn倾向于将轴突聚集在肾小球的前-背域上，这被认为参与了对OB上脂肪族化合物的反应。

It is well accepted that each olfactory sensory neuron (OSN) expresses only one odorant receptor (OR) gene in a mutually exclusive and monoallelic manner. In situ hybridization (ISH) with OR gene probes has demonstrated that the olfactory epithelium (OE) can be divided into four topographically distinct zones and that OSNs expressing a given OR gene are randomly distributed within one zone. The OR genes of various vertebrate species are classified phylogenetically into two different groups, class I and class II. Class I OR genes, first identified in fish and later found in amphibians, were thought to have water-soluble odorous ligands. Class II ORs, which are terrestrial specific, account for a large share of the mammalian OR repertoire and have been investigated in detail in the mouse olfactory system. Recently, we have found that the expression areas are specific to each class II OR gene and are arranged in an overlapping manner in the OE. In contrast, the expression patterns and projection sites for class I ORs are not fully understood. In the present study, we systematically analyzed mouse class I OR genes (42 subfamilies) to elucidate the expression profiles in the OE and the projection sites of their OSNs in the OB. ISH revealed that most class I OR genes (36 subfamilies) were expressed in the dorso-medial zone (zone 1) of the OE. Furthermore, there appeared to be no significant differences in the distributions of OSNs expressing class I genes within zone 1. These results indicate that there is a clear boundary between zone 1 and non-zone 1 areas in the OE. Some class I ORs are known to possess ligand specificity for aliphatic acids, aldehydes and alcohols. Our ISH analysis has revealed that OSNs expressing the class I ORs in zone 1 tend to converge their axons on a cluster of glomeruli in an antero-dorsal domain that is assumed to be involved in responses to the aliphatic compounds on the OB.