Regulation of Cell-extracellular Matrix Interactions at the Brain Surface

脑表面细胞-细胞外基质相互作用的调节

基本信息

批准号：
8304267
负责人：
HUAIYU HU
金额：
$ 27.87万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-20 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8304267
关键词：
Area Astrocytes Basement membrane Binding Brain Cells Cerebral cortex Coculture Techniques Development Dolichyl-phosphate-mannose-protein mannosyltransferase Dystroglycan ECM receptor Enzymes Extracellular Matrix Fibroblasts Gene Delivery Genes Glycoproteins Goals Hereditary Disease Integrins Knock-out Knockout Mice Knowledge Label Lead Light Link Maintenance Mannose Mediating Meningeal Meninges Molecular Movement Muscle eye brain disease Muscular Dystrophies Mutation N-Acetylglucosaminyltransferases Neuroglia Neurons Pathogenesis Physiologic pulse Play Polysaccharides Proteins Radial Regulation Research Role Surface System Walker-Warburg syndrome abstracting brain malformation cell motility congenital muscular dystrophy gene therapy glycosylation glycosyltransferase improved insight lissencephaly meetings overexpression prevent protein function receptor restoration

项目摘要

Abstract Congenital muscular dystrophies (CMDs) with brain malformations are genetic diseases. Brain malformation involves movement of neurons out of the cerebral cortex through breaches of the pial basement membrane (PBM). We propose to study the critical molecules underlying formation of the PBM by radial glia. O-mannosyl glycosylation appears to have an important role. Also further studies of POMT2 conditional knockout mice may shed light on disruptions of the PBM that mediate migration of cells out of the brain. Our hypothesis is that radial glia have a key role in assembling the PBM. Specific Aims are to investigate: 1. The role of radial glia in assembly of the pial basement membrane (PBM). 2. The mechanisms of PBM abnormalities in POMT2 knockout mice. 3. The feasibility of using Large in gene therapy. The proposed research will provide new and important insights into how protein O- mannosyl glycosylation regulates the formation and maintenance of the PBM. It should also yield insights on mechanisms underlying brain malformations in type II lissencephaly. Better knowledge of the key molecules involved in PBM disruptions should lead to potential gene therapies. Gene delivery to restore protein functions should be directed at those cells that organize the formation of the PBM. The proposed research should lead to an improved understanding of the pathogenesis of muscular dystrophies in general and their treatment. 1

抽象的先天性肌肉营养不良（CMDS）具有脑畸形是遗传疾病。大脑畸形涉及神经元从大脑皮层中移动皮层基底膜（PBM）。我们建议研究基础的关键分子 radial胶质细胞形成PBM。 O-甘露糖基糖基化似乎具有重要作用。还进一步研究了有条件敲除小鼠的进一步研究 PBM介导细胞从大脑中迁移。我们的假设是径向颅神经胶质有一个在组装PBM中的关键作用。具体目的是调查： 1。径向神经胶质在丘陵地下膜（PBM）组装中的作用。 2。POMT2敲除小鼠中PBM异常的机制。 3。在基因治疗中使用大型的可行性。拟议的研究将为蛋白质O-如何提供新的重要见解甘露糖基化调节PBM的形成和维持。它也应该产生对II型脑畸形脑畸形的机制的见解。更好的了解PBM中断涉及的关键分子应导致潜在基因疗法。基因输送以恢复蛋白质功能，应针对那些细胞组织PBM的形成。拟议的研究应导致改进一般而言，了解肌肉营养不良的发病机理及其治疗。 1