Glial and axonal interactions mediating olfactory receptor axon sorting

在发育过程中，根据轴突的靶目标对轴突进行分类是轴突引导的关键 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。 但对轴突的全面理解需要了解细胞和分子的基础，而不是 不仅是神经元与神经元之间的相互作用，也包括神经胶质细胞与神经元之间的相互作用。这项提议侧重于互惠。 嗅觉发育过程中嗅觉轴突分类的神经胶质-神经元相互作用 尤其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， 嗅觉感受器神经元的轴突必须脱离它们在 并形成新的气味反应特定关系。在六分蛾Manduca sexta中，ORN轴突分类 神经的一个离散的、高度可及的、富含胶质细胞的区域，从感觉上皮延伸到 大脑。发育是由ORN轴突启动的；后来到达的轴突突然改变了它们的生长模式，并 一旦他们进入这个“分类区域”，他们的联系就会立即发生。重要的是，轴突必须与胶质细胞相互作用。 细胞正确地分类成束状物，送往嗅叶的肾小球。因此，分类区域是 Manduca是一种特别有利的准备材料，用于询问有关胶质细胞-轴突信号机制的问题 潜在的轴突分类和分束。这些研究使用体内和体外并行的方法来测试 神经胶质细胞调节特定正性(例如，促进生长或黏附)和 引导ORN轴突分类的负面(例如，生长抑制或排斥)线索。EM，共焦和现场直播- 细胞显微镜将被用来分析细胞黏附分子Fasciclin II和Fasciclin II的贡献 神经胶质细胞、受体酪氨酸激酶EGFR和FGFR以及轴突的EphR/EPhin信号系统 分类。Manduca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 这是一个学习排序的有用模型。 相关性：长期目标是阐明神经胶质细胞-神经元相互作用的机制，这些机制可能 这在嗅觉发育和许多其他中枢神经系统通路的发育中是共同的。了解这些 神经元-神经胶质细胞的相互作用将有助于奠定战胜毁灭性打击的基础 神经系统发育异常和受伤后再生能力不足。

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.