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 当配体与分子受体结合时，气味感知开始于嗅上皮（OE 在嗅觉感觉神经元（OSN）的纤毛上表达。巴克和阿克塞尔（1991）是第一个 描述了编码气味受体（ORs）的基因大家族，目前已知的数量约为1,200个， 小鼠OSN仅表达1个OR。表达相同OR的OSN不聚类，而是广泛地 因此，OE是一个复杂的神经元镶嵌体，每个神经元仅表达 1,200个可能的手术室当OSN轴突离开OE时，它们最初与最近的邻居成束，而不是 必然具有来自表达相同OR的OSN的轴突。然而，当它们在地表上前进时 从嗅球到肾小球会聚点，轴突经历了深刻的地形学变化。 重组，使得来自表达相同OR的神经元的所有轴突仅会聚成 2/3肾小球/嗅球。这个轴突重组和汇聚成特定肾小球的过程 在脊椎动物中是广泛保守的，并提出了一个重要的布线问题，也许是最复杂的 感觉系统中的布线问题。尽管大家都在努力寻找 OSN轴突的生长，合并和靶向，我们仍然可悲地忽视了最基本的 轴突的方面：轴突相互作用：OSN轴突的重组如何与OSN的组织相关？ 它们的轴骨架和细胞器当轴突最初成束时， 当它们在嗅神经层中解束时，形成新的OR同型 针对特定肾小球的纤维束？是什么驱动OSN轴突的成束/去成束; 涉及机械力？我们什么时候能识别出同型肌束震颤？什么是时间轴 OSNs的成熟以及它如何与轴突延伸到OB靶点和功能相关 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 发展遵循同样的基本规律。因此，除了研究轴突：轴突相互作用和 在小鼠的超微结构中，我们引入了一种新的模型，斑马鱼活体成像，以评估 OSN轴突：发育过程中轴突的相互作用。为了开始解决这些重大差距， 知识，我们提出了3个具体的目标：目标1 -测试假设的细胞骨架组织 嗅神经层内、外板层内的OSN轴突及其成束 嗅球目的2 -测试轴骨动力学以及机械力的假设， 控制活斑马鱼中OSN轴突的成束/去束和导航。目标3 -测试 假设OSN轴突延伸的时空动力学和细胞骨架蛋白的表达 和粘附分子在围产期与成年小鼠中不同。

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