权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Characterization of the cellular and molecular mechanisms that mediate glial tiling

介导神经胶质平铺的细胞和分子机制的表征

基本信息

批准号：
9975244
负责人：
Sarah C Kucenas
金额：
$ 34.81万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975244
关键词：
Animal Model Apoptosis Axon Behavior Candidate Disease Gene Cell Communication Cells Central Nervous System Degenerative Diseases Clustered Regularly Interspaced Short Palindromic Repeats Collection Color Cues Data Development Diagnosis Disease Dorsal Electron Microscopy Event Extracellular Matrix Future Genes Genome Image Injury Light Location Mediating Mediator of activation protein Modification Molecular Motor Motor Neurons Myelin Nature Nervous system structure Neuroglia Oligodendroglia Peripheral Nervous System Pharmacology Physiological Plant Roots Play Population Positioning Attribute Process Radial Receptor Signaling Resources Role Schwann Cells Specific qualifier value Spinal Spinal Cord Spinal nerve structure System Time Transgenic Organisms Zebrafish cell behavior genetic manipulation gliogenesis in vivo insight migration neurotransmission novel oligodendrocyte progenitor relating to nervous system screening small molecule stem cells

项目摘要

Development of a functional and efficient nervous system requires the orchestrated specification, migration and differentiation of glia. During gliogenesis in both the central and peripheral nervous systems (CNS and PNS, respectively), large populations of glia are specified that must migrate and differentiate into not only functional glial cells, but also coordinate their development so that they occupy discrete, non-overlapping territories with neighboring glia. This phenomenon of glial spacing, or tiling, can occur between glia found in the CNS, PNS, or between glial cells where one cell resides in the CNS and the other resides in the PNS. Although we know that these tiling events occur, we don’t know the molecular nature of these interactions or whether they are used by all tiling glia. Additionally, how local glial-glial interactions play a role in global glial tiling is unknown. In this proposal, using zebrafish as a model organism, we will investigate the cellular and molecular mechanisms that mediate pre-myelinating glial tiling at motor exit point (MEP) transition zones (TZ) and in the developing spinal cord. In Aim 1 of this project, we will use a combination of expression analysis, multi-color, in vivo, time-lapse imaging, electron microscopy, pharmacological and genetic manipulation (CRISPR) of newly identified mediators to elucidate the cellular and molecular mechanisms that govern myelinating glial tiling at MEP TZs. In Aim 2, we will determine if the same mechanisms we characterize in Aim 1 also mediate tiling between oligodendrocyte progenitor cells (OPC) in the developing spinal cord. To better understand, diagnose and treat the many degenerative disorders of the CNS and PNS, we need to comprehend the cellular and molecular mechanisms that mediate glial-glial interactions and tiling. Zebrafish provide a unique opportunity to directly observe and manipulate cell populations to gain insight into how glial cells interact under normal physiological conditions, and if those interactions that ultimately result in glial tiling are perturbed in disease.

功能和高效的神经系统的发展需要精心安排的规范，迁移和