Mechanisms of Developmental Plasticity in the Mammalian Olfactory System

哺乳动物嗅觉系统发育可塑性机制

基本信息

批准号：
10174905
负责人：
Congrong Ron Yu
金额：
$ 47.27万
依托单位：
STOWERS INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10174905
关键词：
Adult Affect Aging Alzheimer&apos s Disease Animals Axon Behavior Birth Brain Candidate Disease Gene Continuous Infusion Data Development Developmental Process Embryo Failure Gene Expression Profile Genes Genetic Goals Growth Impairment Knowledge Label Lead Life Maps Molecular Motivation Mus Natural regeneration Nerve Regeneration Nervous System Physiology Nervous system structure Neurodegenerative Disorders Neurons Olfactory Epithelium Olfactory Pathways Parkinson Disease Pathologic Pattern Perinatal Play Positioning Attribute Process Quality of life Regenerative Medicine Regenerative capacity Regulation Role Sensory Structure System Systems Development Testing WNT Signaling Pathway adult neurogenesis axonal pathfinding brain cell critical period deprivation developmental plasticity experimental study functional restoration genetic manipulation genetic testing innovation insight loss of function mature animal nerve stem cell neurodevelopment neuron development novel novel strategies olfactory bulb olfactory sensory neurons postnatal postnatal development postnatal period preventive intervention programs public health relevance receptor regenerative repair relating to nervous system repaired scaffold sensory system single-cell RNA sequencing transcriptome

项目摘要

Project Summary/Abstract. In the mammalian brain, the olfactory bulb is the only region that receives not only continuous infusion of neuronal progenitor cells from the brain, but also renewed input from the olfactory epithelium. The olfactory sensory neurons (OSNs) continuously regenerate throughout the life of the animal. The newly-generated OSNs project precisely to stereotypical positions in the olfactory bulb to maintain a sensory map. It has been thought that the olfactory system does not exhibit a critical period during development because of its unique, continuous regenerative capacity. Our recent results show that axonal targeting of the OSNs is sensitive to deprivation of neural activity and other perturbations during the first postnatal week in olfactory development, suggesting a critical period in OSN axon targeting. Our data further suggest that two separate developmental programs underlie the precise targeting of the OSNs before and after the critical period. The switch is accompanied by a prominent change in the patterns of gene expression. The objective of this application is to determine the molecular control of the critical period in olfactory system development. By combining genetic manipulation and transcriptome analyses, we have developed approaches that allow us to directly compare the developmental programs during early postnatal period and in adulthood. We have identified candidate genes and we will test their role in determining the axon dynamics during the critical period and their role in determining the timing of the critical period. These studies will provide mechanistic insights into axon pathfinding during OSN development and during adult neurogenesis.

项目摘要/摘要。在哺乳动物的大脑中，嗅球是唯一一个不仅接受连续输入的区域来自大脑的神经元祖细胞，也来自嗅觉上皮的更新输入。嗅觉感觉神经元（OSN）在动物的一生中不断再生。新生成的 OSN 精确投射到嗅球中的典型位置，以维持感觉图。它一直认为嗅觉系统由于其独特的、持续的再生能力。我们最近的结果表明 OSN 的轴突靶向对出生后第一周嗅觉发育中神经活动的剥夺和其他干扰，这表明 OSN 轴突靶向的关键时期。我们的数据进一步表明，两个独立的发育计划是关键时期前后 OSN 精确定位的基础。开关是伴随着基因表达模式的显着变化。该应用程序的目的是确定嗅觉系统发育关键期的分子控制。通过结合遗传通过操作和转录组分析，我们开发了一些方法，使我们能够直接比较产后早期和成年期的发育计划。我们已经确定了候选基因我们将测试它们在确定关键时期轴突动态方面的作用以及它们在确定关键期的时间。这些研究将为轴突提供机制见解 OSN 发育和成人神经发生过程中的寻路。