Glial and axonal interactions mediating olfactory receptor axon sorting

根据它们的靶目的地对轴突进行分类对于发育中的轴突引导是必不可少的。 神经系统细胞间的相互作用在几乎所有的实验模型中都被证明是至关重要的 轴突的指导，但一个完整的理解需要知道细胞和分子的基础， 不仅是神经元之间的相互作用，也是神经胶质细胞之间的相互作用。该提案侧重于互惠 嗅觉发育过程中嗅觉轴突分类的胶质-神经元相互作用 通路，特别是神经胶质细胞在调节特定信号通路中的作用。在开发过程中， 嗅觉受体神经元（ORN）的轴突必须摆脱它们在大脑中建立的轴突联系。 外围和形成新的气味反应特定的关系。在天蛾Manduca sexta中，ORN轴突 一个离散的，高度可及的，神经胶质丰富的区域，从感觉上皮延伸到 个脑袋发育由ORN轴突启动;后来到达的轴突突然改变其生长模式， 他们一进入这个“分类区”就开始联系。重要的是，轴突必须与神经胶质细胞相互作用， 细胞正确地分类成束，注定在嗅叶肾小球。因此， Manduca是一个特别有利的准备问有关胶质轴突信号机制的问题 轴突分类和成束的潜在机制这些研究使用平行的体内和体外方法来测试 假设神经胶质细胞调节特异性阳性（例如，生长促进剂或粘合剂）和 负的（例如，生长抑制或排斥）的线索，指导ORN轴突的分类。EM，共聚焦和实时- 细胞显微镜将用于测定细胞粘附分子Fasciclin II和 神经胶质细胞、受体酪氨酸激酶EGFR和FGFR以及EphR/ephrin信号系统对轴突的影响 分类曼杜卡的嗅觉系统与哺乳动物的嗅觉系统有足够的复杂性和相似性， 一个研究排序的有用模型。 相关性：长期目标是阐明可能导致神经胶质细胞-神经元相互作用的机制。 嗅觉发育和许多其他中枢神经系统通路的发展是共同的。了解这些 相互的神经元-神经胶质相互作用将有助于建立战胜毁灭性疾病的基础。 神经系统发育异常和损伤后再生尝试不足。

Sorting of axons according to their target destination is essential for axonal guidance in the developing nervous system. Intercellular interactions have been shown in virtually all experimental models to be critical in axon guidance, but a full understanding requires knowing the cellular and molecular underpinnings not only of neuron-neuron interactions but also of glia-neuron interactions. This proposal focuseson reciprocal glia-neuron interactions underlying the sorting of olfactory axons during development of the olfactory pathway, especially on the role of glial cells in regulating specific signaling pathways. During development, the axons of olfactory receptor neurons (ORNs) must shed the axonal associations they established in the periphery and form new odor response-specific relationships. In the moth Manduca sexta, ORN axons sort in a discrete, highly accessible, glia-rich region of the nerve that extends from the sensory epithelium to the brain. Development is initiated by ORN axons; later arriving axons abruptly change their growth pattern and their associations as soon as they enter this "sorting zone". Importantly, the axons must interact with the glial cells to sort properly into fascicles destined for glomeruli in the olfactory lobe. Thus the sorting zone of Manduca is an especially advantageous preparation to ask questions about glia-axon signaling mechanisms underlying axon sorting and fasciculation. The studies use parallel in vivo and in vitro approaches to test the hypothesis that glial cells regulate the balance of specific positive (e.g., growth-promoting or adhesive) and negative (e.g., growth-inhibiting or repulsive) cues that guides sorting of ORN axons. EM, confocal and live- cell microscopy will be used to assay the contributions of the cell adhesion molecules Fasciclin II and Neuroglian, the receptor tyrosine kinases EGFR and FGFR, and the EphR/ephrin signaling systemto axonal sorting. Manduca's olfactory system has sufficient complexity and similarity to the mammalian systemto be a useful model in which to study sorting. Relevance : The long term goal is to elucidate the mechanisms of glia-neuron interactions that are likely to be common to olfactory development and development of many other CNS pathways. Understanding these reciprocal neuron-glia interactions will contribute to the foundation needed to conquer devastating developmental abnormalities of the nervous system and inadequate regenerative attempts following injury.