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Adhesion G protein-coupled receptors in CNS development and regeneration

CNS发育和再生中的粘附G蛋白偶联受体

基本信息

批准号：
9145803
负责人：
Xianhua Piao
金额：
$ 39.25万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9145803
关键词：
ADGR1 gene Adhesions Affect Alleles Antithymoglobulin Astrocytes Axon Bilateral Binding Biochemical Biological Biology Biotinylation Brain Caliber Cell Cycle Cells Cerebral cortex Cerebrum Clinical Communication Corpus Callosum Cuprizone Data Defect Demyelinating Diseases Demyelinations Development Disease Exons Extracellular Matrix Extracellular Matrix Proteins Family Family member G-Protein-Coupled Receptors Genetic Health Human Image Injury Knock-out Knockout Mice Lesion Ligands Magnetic Resonance Imaging Mediating Membrane Microgyria Modeling Molecular Multiple Sclerosis Mus Mutation Myelin Myelin Sheath Natural regeneration Nervous System Physiology Nervous system structure Neuraxis Neuroglia Oligodendroglia Patients Phenotype Play Property Proteomics RNA Splicing Role Signal Transduction Stem cells Testing Tissues Toxin Transgenic Mice Transglutaminases Up-Regulation Validation Variant Work astrocyte progenitor brain malformation cell type design glial cell development in vivo myelination nervous system development nervous system disorder new therapeutic target novel oligodendrocyte lineage oligodendrocyte precursor precursor cell prevent receptor remyelination repaired therapeutic target white matter

项目摘要

DESCRIPTION (provided by applicant): Myelin is the multilayered membrane generated by glial cells that insulates and protects axons in the vertebrate nervous system. In the central nervous system (CNS), oligodendrocytes (OLs) form the myelin sheath. The molecular mechanisms that govern oligodendrocyte development, myelination, and myelin repair are poorly understood; myelin is disrupted in many neurological diseases, and so a better understanding of OL biology has important clinical implications. The object of this proposal is to study how the adhesion G protein- coupled receptor GPR56 regulates OL development, myelination, and myelin repair. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP), in which the normal cortical folds of the cerebrum are replaced by numerous small gyri. In addition to the poor formation of the cerebral cortex, white matter is also adversely affected in BFPP patients. MRI images of BFPP brains reveal signal changes indicating myelination defects. Furthermore, our preliminary studies demonstrate that: 1) GPR56 is expressed in oligodendrocyte progenitor cells (OPCs) and immature OLs; 2) disruption of Gpr56 leads to CNS myelin defects in mice; and 3) there is a novel putative ligand of GPR56 in CNS. Taken together, our data support the hypothesis that GPR56 is a previously unappreciated regulator of myelination in the CNS. This proposal is designed to test this hypothesis, thus establishing novel regulators of glial cell development and myelination. Our work is likely to enhance the understanding of the basic biology of myelination and will potentially reveal a new target for therapeutics to promote repair in myelin disease.