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

The role of dystroglycan in neural circuit development.

肌营养不良聚糖在神经回路发育中的作用。

基本信息

批准号：
9308019
负责人：
Kevin Wright
金额：
$ 33.69万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9308019
关键词：
Affect Alleles Axon Binding Biochemical Cell Surface Receptors Cell physiology Cues Cytoskeleton Defect Development Dystroglycan Employee Strikes Environment Extracellular Matrix Extracellular Protein Genes Genetic Genetic Screening Glycoproteins Human In Vitro Individual Instruction Integral Membrane Protein Lead Ligand Binding Link Modeling Molecular Morphology Mus Mutant Strains Mice Mutation Nervous system structure Neurodevelopmental Disorder Neurons Pathway interactions Pattern Population Process Prosencephalon Proteins Regulation Role Series Signal Pathway Signal Transduction Spinal Cord Synapses System Testing axon guidance congenital muscular dystrophy dystroglycanopathy experimental study extracellular glycosylation glycosyltransferase in vivo insight migration mild cognitive impairment mouse model mutant neural circuit neurodevelopment novel planar cell polarity postsynaptic synaptogenesis

项目摘要

Project Summary The formation of functional neural circuits requires the proper migration of newly generated neurons, precise guidance of axons to the appropriate postsynaptic targets, the formation of elaborate dendritic arbors and establishment of synaptic connections. These processes depend on the reiterative use of cell-surface receptors throughout development that respond to instructive cues present in the extracellular environment. The transmembrane glycoprotein dystroglycan is involved in multiple aspects of neural circuit development, including axon guidance and dendritic arborization. The objective of this proposal is to define the specific molecular pathways that dystroglycan functions within to regulate these processes. The first aim tests the hypothesis that dystroglycan interacts with the planar cell polarity (PCP) protein Celsr3 to regulate axon guidance. The experiments proposed in this aim will define which cellular populations dystroglycan functions in to regulate axon guidance in vivo, determine how dystroglycan and Celsr3 interact in vitro and in vivo and investigate how the loss of dystroglycan affects signaling downstream of PCP pathway activation. The second aim will focus on understanding the role of dystroglycan in regulating dendritic arborization. Specifically, the experiments outlined will examine how dendritic morphology is affected in models of dystroglycanopathy, determine if dystroglycan functions cell-autonomously and provide mechanistic insight into the intracellular signaling cascades downstream of dystroglycan that regulate dendritic morphology. Taken together, the proposed experiments will define the role of dystroglycan in regulating multiple aspects of neural circuit development and provide insight into how these processes are affected in individuals with mutations that affect normal dystroglycan function.

项目总结