Dynamic interactions among olfactory sensory neuron axons

嗅觉感觉神经元轴突之间的动态相互作用

• 批准号: 10685631
• 负责人: Charles A Greer
• 金额: $ 41.48万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10685631
• 关键词: Address; Adhesions; Adult; Affect; Area; Array tomography; Axon; Binding; Brain; Cell Adhesion Molecules; Cells; Central Nervous System; Cilia; Code; Collaborations; Complex; Cytoskeletal Modeling; Cytoskeleton; Data; Development; Epithelium; Exhibits; Extracellular Space; Fascicle; Gene Family; Genetic; Genetically Engineered Mouse; Image; Knowledge; Life; Ligand Binding; Location; Mechanics; Modeling; Molecular; Mus; Muscle fasciculation; Natural regeneration; Nature; Neurons; Nose; Odorant Receptors; Olfactory Epithelium; Olfactory Nerve; Olfactory Pathways; Olfactory tract; Organelles; Pathway interactions; Perinatal; Population; Process; Property; Regulation; Role; Side; Site; Smell Perception; Specificity; Structure-Activity Relationship; Sum; Surface; Systems Development; Testing; Transmission Electron Microscopy; Vertebrates; Work; Zebrafish; axon growth; axon regeneration; improved; in vivo; innovation; insight; mechanical force; mosaic; neuron development; olfactory bulb; olfactory neurogenesis; olfactory sensory neurons; protein expression; receptor; receptor expression; sensory system; spatiotemporal; timeline

Project Summary – Abstract Odor perception begins in the olfactory epithelium (OE) when ligands bind to molecular receptors expressed on the cilia of the olfactory sensory neurons (OSNs). Buck and Axel (1991) were the first to describe the large family of genes coding for the odorant receptors (ORs), now known to number ~1,200 in mice. An OSN expresses only 1 OR. OSNs expressing the same OR do not cluster but rather are broadly distributed across the OE. Thus, the OE is a complex mosaic of neurons each of which expresses only 1 of 1,200 possible ORs. As OSN axons exit the OE they initially fasciculate with nearest neighbors, not necessarily with axons from OSNs expressing the same OR. However, as they progress over the surface of the olfactory bulb to a point of glomerular convergence, the axons undergo a profound topographical reorganization such that all of the axons coming from neurons expressing the same OR converge into only 2/3 glomeruli/olfactory bulb. This process of reorganization of axons and convergence into specific glomeruli is broadly conserved among vertebrates and poses a significant wiring problem, perhaps the most complex wiring problem found among sensory systems. Despite concerted efforts to identify the molecular substrates of OSN axon growth, coalescence and targeting, we remain woefully ignorant of the most fundamental aspects of axon:axon interactions: How does the reorganization of OSN axons relate to the organization of their axoskeleton and organelles? What are the axoskeleton dynamics as axons initially fasciculate and extend toward the OB and when they defasciculate in the olfactory nerve layer, forming new OR homotypic fascicles targeted to specific glomerului? What drives fasciculation/defasciculation of OSN axons; are mechanical forces involved? When do we recognize homotypic fasciculation? What is the timeline for the maturation of OSNs and how does it relate to the extension of the axon to OB targets and functional activity? Importantly, these fundamental questions apply equally to all vertebrates, in which olfactory system development obeys the same basic rules. Thus here, in addition to studies of axon:axon interactions and ultrastructure in mice, we introduce a new model, live imaging in zebrafish, to assess the dynamic nature of OSN axon:axon interactions during development. To begin addressing these significant gaps in our knowledge we propose 3 specific aims: Aim 1 - Test hypotheses regarding the cytoskeletal organization of OSN axons and their fasciculation in the inner and outer sublaminae of the olfactory nerve layer of the olfactory bulb. Aim 2 – Test the hypotheses that the axoskeleton dynamics, as well as mechanical forces, control the fasciculation/defasciculation and navigation of OSN axons in the live zebrafish. Aim 3 – Test the hypothesis that the spatio-temporal dynamics of OSN axon extension and the expression of cytoskeletal and adhesion molecules differ in perinatal versus adult mice.

项目摘要 - 摘要 当配体与分子接收器结合时，气味感知始于嗅觉上皮（OE） 在嗅觉感觉神经元（OSN）的纤毛上表达。 Buck and Axel（1991）是第一个 描述编码的大型基因家族（ORS），现在已知数字〜1,200 老鼠。 OSN仅表示1或。 OSN表达相同或不集群，而是广泛的 分布在OE上。那就是OE是神经元的复杂镶嵌物，每个神经元仅表示1个 1,200个可能的OR。当OSN轴突退出OE时，它们最初与最近的邻居着迷，而不是 必须使用来自OSN的轴突表示相同或。但是，随着它们在表面上的发展 嗅球到肾小球收敛的点，轴突经历了深刻的地形 重组使所有来自表达相同神经元或仅收敛到的神经元的轴突 2/3肾小球/嗅球。轴突和收敛到特定glomerulli的重组过程 在脊椎动物中广泛保守，并提出一个重大的布线问题，也许是最复杂的 接线问题在感觉系统中发现。尽管共同努力确定分子底物 在OSN轴突生长，合并和靶向上，我们对最基本的最基本无知 轴突的各个方面：轴突相互作用：OSN轴突的重组与组织的组织如何 他们的轴骨骼和细胞器？作为轴突，轴骨骼动力学最初是什么，并且 延伸到OB，当它们在嗅觉神经层中降临时，形成新的或同型 针对特定肾小球的束？驱动OSN轴突的诱发/缺乏的是什么？是 机械力涉及？我们什么时候认识同种异体的诱惑？什么是时间表 OSN的成熟及其与轴突扩展到OB目标和功能的关系 活动？重要的是，这些基本问题同样适用于所有脊椎动物，其中嗅觉系统 发展遵守相同的基本规则。在这里，除了对轴突的研究：轴突相互作用和 在小鼠的超微结构中，我们引入了一种新模型，斑马鱼中的实时成像，以评估动态性质 OSN轴突：开发过程中的轴突相互作用。开始解决我们的这些重大差距 知识我们提出3个具体目的：目标1-测试有关细胞骨架组织的假设 OSN轴突及其在嗅觉神经层的内部和外sublaminae中 嗅球。目标2 - 检验轴骨骼动力学以及机械力的假设 控制活斑马鱼中OSN轴突的束缚/缺乏和导航。 AIM 3 - 测试 假设OSN轴突延伸的时空动力学和细胞骨架的表达 围产期与成年小鼠的粘附分子不同。

项目成果

Actomyosin contractility in olfactory placode neurons opens the skin epithelium to form the zebrafish nostril.

嗅板神经元中的肌动球蛋白收缩性打开皮肤上皮形成斑马鱼鼻孔。

• DOI: 10.1016/j.devcel.2023.02.001
• 发表时间: 2023
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: Baraban,Marion;GordilloPi,Clara;Bonnet,Isabelle;Gilles,Jean-François;Lejeune,Camille;Cabrera,Mélody;Tep,Florian;Breau,MarieAnne
• 通讯作者: Breau,MarieAnne