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

Role of mPAR6 Polarity CNS Neuronal Migration

mPAR6 极性中枢神经系统神经元迁移的作用

基本信息

批准号：
7569420
负责人：
Mary Elizabeth Hatten
金额：
$ 41.02万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-02 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7569420
关键词：
Acute Adult Animals Anterior Attention Binding Biological Models Brain Caenorhabditis elegans Cell Nucleus Cell division Centrosome Complex Congenital Abnormality Cytoplasmic Granules Defect Development Dominant-Negative Mutation Dyes Ephrin-B1 Ephrin-B2 Ephrins Epilepsy Evolution Family Fiber Genes Genetic Goals Human Immigration In Vitro Ion Channel Kinesin Label Lasers Learning Disabilities Ligands Light Link Locomotion Mammalian Cell Mental Retardation Methods Molecular Monitor Motion Movement Neurons Nuclear Nuclear Translocation PAR-6 protein Pathway interactions Positioning Attribute Process Proteins Publishing Receptor Protein-Tyrosine Kinases Receptor Signaling Regulation Research Role Signal Pathway Signal Transduction Site Slice Stroke Synaptic plasticity System Testing Tissues Transgenic Mice axon guidance cell motility chromophore gene function granule cell human JTB protein in vivo insight loss of function migration mutant novel protein complex receptor research study rho GTP-Binding Proteins small hairpin RNA

项目摘要

The migration of young neurons from sites where they are generated into the positions where they establish the circuitry of the adult brain is a critical step in development. Defects in migration cause a host of human birth defects, ranging from severe mental retardation to subtle learning disabilities, as well as a large number of the epilepsies. Our lab has focused on understanding the genes that control migration, in the hope that insights into this key step in normal development. We use the migration of the cerebellar granule neuron as a model system to examine the molecular control of glial-guided neuronal migration. The establishment of neuronal polarity is a key step in initiating neuronal migration along the glial guide. Screens for genes that function in granule neuron migration revealed high levels of expression of the polarity signaling complex mPar6a neurons exiting the cycle and establishing polarity. In C. elegans, a set of 6 PAR proteins establish anterior/posterior asymmetries and control subsequent asymmetric cell divisions. PAR proteins are conserved throughout evolution. In Preliminary Studies (Solecki et al, 2004), we discovered that the mParGa signaling complex is localized in the centrosome of migrating cerebellar granule neurons, where it coordinates the movement of the centrosome and the nucleus as the neuron migrates along the glial fiber. In the proposed research, we will study the other components of the mParGa complex, aPKC^ and Par3, in the polarity of migrating granule neurons. The role of mPartxx in cell division suggests that targeted loss of function mutants and shRNA experiments will not be feasible. We will therefore use a novel method developed by Roger Tsien to incorporate a genetic tag (TC) which binds the dye ReAshS, into mParGq and use chromophore-assisted light inactivation with a monochromatic laser to inactivate mParGa in the centrosome. For those experiments, we will generate TC-mPar6a BAG transgenic mice, enabling studies on granule cells and cortical neurons. In a final group of experiments, we will study a receptor/ligand system expressed in granule cells which interacts with the mParGa complex, the EphB ligands ephrin-B1 and ephrin-B2. Together, these experiments will provide novel information on the regulation of neuronal migration in cortical regions of developing brain.

年轻的神经元从它们产生的地方迁移到