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

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