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.

项目总结 – 摘要 当配体与分子受体结合时，气味感知开始于嗅觉上皮 (OE) Buck 和 Axel (1991) 最先发现了嗅觉感觉神经元 (OSN) 纤毛上的表达。 描述了编码气味受体 (OR) 的基因大家族，目前已知数量约为 1,200 个 一个 OSN 只表达 1 个 OR，表达相同 OR 的 OSN 不会聚集，而是广泛分布。 因此，OE 是一个复杂的神经元镶嵌体，每个神经元仅表达 1 个神经元。 1,200 个可能的 ORs 当 OSN 轴突离开 OE 时，它们最初与最近的邻居聚集，而不是与最近的邻居聚集。 必然具有表达相同 OR 的 OSN 轴突，但是，当它们在表面上前进时。 从嗅球到肾小球会聚点，轴突经历了深刻的地形变化 重组，使得来自表达相同 OR 的神经元的所有轴突仅汇聚成 2/3 肾小球/嗅球 轴突重组并汇聚成特定肾小球的过程。 在脊椎动物中广泛保守，并造成严重的接线问题，也许是最复杂的 尽管共同努力识别分子底物，但在感觉系统中发现了接线问题。 关于 OSN 轴突的生长、合并和靶向，我们仍然对最基本的知识一无所知 轴突：轴突相互作用的各个方面：OSN 轴突的重组与轴突的组织有何关系 它们的轴骨骼和细胞器是什么？轴突最初束状和收缩时的轴骨骼动力学是什么？ 向 OB 延伸，当它们在嗅觉神经层中解束时，形成新的 OR 同型 靶向特定肾小球的束是什么驱动 OSN 轴突的束颤/解束？ 涉及机械力？我们什么时候认识到同型颤动？ OSN 的成熟及其与轴突向 OB 目标和功能的延伸有何关系 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 因此，除了轴突：轴突相互作用的研究之外，发育遵循相同的基本规则。 为了评估小鼠的超微结构，我们引入了一种新模型，即斑马鱼的实时成像，以评估超微结构的动态性质 OSN 轴突：发育过程中的轴突相互作用开始解决我们的这些重大差距。 基于这些知识，我们提出了 3 个具体目标： 目标 1 - 测试有关细胞骨架组织的假设 OSN 轴突及其在嗅神经层内、外亚层中的束状运动 目标 2 – 测试轴骨骼动力学以及机械力的假设。 控制活体斑马鱼 OSN 轴突的束颤/去束颤和导航 目标 3 – 测试 假设 OSN 轴突延伸的时空动力学和细胞骨架的表达 和粘附分子在围产期小鼠与成年小鼠中有所不同。

项目成果

Chemical and mechanical control of axon fasciculation and defasciculation.

轴突束颤和去束颤的化学和机械控制。

• 发表时间: 2023-05-15
• 影响因子: 7.3
• 作者: Breau, Marie Anne;Trembleau, Alain
• 通讯作者: Trembleau, Alain

Intertissue mechanical interactions shape the olfactory circuit in zebrafish.

组织间的机械相互作用塑造了斑马鱼的嗅觉回路。

• 发表时间: 2022-02-03
• 影响因子: 7.7
• 作者: Monnot, Pauline;Gangatharan, Girisaran;Baraban, Marion;Pottin, Karen;Cabrera, Melody;Bonnet, Isabelle;Breau, Marie Anne
• 通讯作者: Breau, Marie Anne

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。

• 发表时间: 2023-03-13
• 影响因子: 11.8
• 作者: Baraban, Marion;Gordillo Pi, Clara;Bonnet, Isabelle;Gilles, Jean;Lejeune, Camille;Cabrera, Mélody;Tep, Florian;Breau, Marie Anne
• 通讯作者: Breau, Marie Anne