DEVELOPMENT AND FUNCTION OF THE MAMMALIAN OLFACTORY SYSTEM

分子神经生物学的研究目标是确定哺乳动物嗅觉系统的发育和功能的分子机制。其中一个重点领域是识别的分子，直接建立精确的模式之间观察到的外周感觉神经元和它们的目标神经元的嗅球突触连接。与其他感觉系统不同的是，在外周内，传入的嗅觉感觉信息几乎没有地形组织。然而，在大脑的嗅球内，存在嗅觉信息的精确空间表示，其中表达相同气味受体的神经元将其轴突投射到相同的次级神经元。介导表达相同受体类型的神经元的轴突的这种会聚的分子机制尚不清楚。据推测，气味受体本身可能参与了这一过程，因此在气味识别和轴突引导中发挥双重作用。已经分离了几种气味受体的全长cDNA克隆，并将其克隆到哺乳动物和昆虫表达载体中，并且正在开发异源细胞表达系统。这样的细胞系应有利于气味受体的功能特性方面的配体特异性和推定的相互作用与延髓位置线索。此外，几个不同的基因家族的成员已牵连在其他系统中的轴突指导正在评估嗅觉系统内的类似作用。这些研究的主要成果是分离出一个新的脑信号蛋白基因家族成员。semaphorin基因家族的几个成员已被证明在体外作为轴突导向分子发挥作用，并且semaD（该家族的IV类成员之一）缺陷的小鼠在特定轴突投射的图案中显示缺陷。Sema4g编码位于小鼠19号染色体上的脑信号蛋白基因家族的一个新的IV类成员。与其他IV类脑信号蛋白基因一样，Sema4G是具有特征性脑信号蛋白和胞外Ig同源结构域的整合膜蛋白。在轴突生长和突触发生期间，它在嗅球中的嗅感觉神经元和它们的突触伙伴中强烈表达。胚胎表达的sema4g也观察到犁鼻器，视网膜和耳蜗的神经上皮细胞，这表明了重要的作用，这些感觉系统的发展中的Sema4G。- 嗅觉系统，轴突导向，原位杂交，气味受体，脑信号蛋白

The research goals of the Section of Molecular Neurobiology are to define the molecular mechanisms underlying the development and function of the mammalian olfactory system. One area of emphasis is the identification of molecules which direct the establishment of the precise patterns of synaptic connectivity observed between peripheral sensory neurons and their target neurons in the olfactory bulb. Unlike other sensory systems, there is little topographic organization of incoming olfactory sensory information within the periphery. However, within the olfactory bulb of the brain, there is a precise spatial representation of olfactory information with neurons expressing the same odorant receptor projecting their axons to the same secondary neurons. The molecular mechanisms mediating this convergence of axons of neurons expressing the same receptor type are not known. It has been hypothesized that the odorant receptors themselves may be involved in this process and thus play dual roles in both odorant recognition and axonal guidance. Full length cDNA clones of several odorant receptors have been isolated and cloned into mammalian and insect expression vectors, and heterologous cell expression systems are being developed. Such cell lines should facilitate the functional characterization of odorant receptors with respect to both ligand specificity and putative interactions with bulbar positional cues. In addition, members of several different gene families which have been implicated in axonal guidance in other systems are being evaluated for similar roles within the olfactory system. The major outcome of these studies has been the isolation of a novel member of the semaphorin gene family. Several members of the semaphorin gene family have been demonstrated to function in vitro as axonal guidance molecules, and mice deficient in semaD, one class IV member of the family, display defects in the patterning of specific axonal projections. Sema4g encodes a novel class IV member of the semaphorin gene family located on mouse chromosome 19. Like other class IV semaphorin genes, Sema4G is an integral membrane protein with characteristic semaphorin and extracellular Ig-homology domains. It is robustly expressed in both olfactory sensory neurons and their synaptic partners in the olfactory bulb during the time when axonal outgrowth and synaptogenesis are occurring. Embryonic expression of sema4g is also observed in the neuroepithelia of the vomeronasal organ, retina, and cochlea suggesting an important role for Sema4G in the development of these sensory systems. - olfactory system, axonal guidance, in situ hybridization, odorant receptors, semaphorin"