DEVELOPMENT AND FUNCTION OF THE MAMMALIAN OLFACTORY SYSTEM

分子神经生物学部分的研究目标是定义哺乳动物嗅觉系统发育和功能的分子机制。一个重点领域是识别分子，这些分子指导建立周围感觉神经元和嗅球中目标神经元之间观察到的突触连接的精确模式。与其他感觉系统不同，传入的嗅觉感觉信息在外围几乎没有地形组织。然而，在大脑的嗅球中，有一种精确的嗅觉信息空间表征，表达相同气味受体的神经元将它们的轴突投射到相同的次级神经元上。介导表达相同受体类型的神经元轴突趋同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起着双重作用。多种气味受体的全长cDNA克隆已被分离并克隆到哺乳动物和昆虫的表达载体上，异源细胞表达系统正在开发中。这样的细胞系应该有助于气味受体在配体特异性和假定的与球位置线索的相互作用方面的功能表征。此外，在其他系统中与轴突引导有关的几个不同基因家族的成员正在评估其在嗅觉系统中的类似作用。这些研究的主要成果是分离出信号蛋白基因家族的一个新成员。信号蛋白基因家族的几个成员已被证明在体外作为轴突引导分子起作用，并且semaD基因家族的第IV类成员缺乏的小鼠在特定轴突投射模式上表现出缺陷。Sema4g编码位于小鼠19号染色体上的信号蛋白基因家族的一个新的IV类成员。与其他IV类信号蛋白基因一样，Sema4G是一种完整的膜蛋白，具有信号蛋白和细胞外ig同源结构域的特征。在轴突生长和突触发生的过程中，它在嗅球的嗅觉感觉神经元及其突触伙伴中都有强烈的表达。sema4g的胚胎表达也在颏鼻器官、视网膜和耳蜗的神经上皮细胞中观察到，这表明sema4g在这些感觉系统的发育中起着重要作用。嗅觉系统，轴突引导，原位杂交，气味受体，信号素

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"