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Role of molecular recognition in retinal patterning and synaptic organization

分子识别在视网膜图案化和突触组织中的作用

基本信息

批准号：
8316275
负责人：
PETER Gerard FUERST
金额：
$ 23.68万
依托单位：
UNIVERSITY OF IDAHO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8316275
关键词：
Adhesions Alleles Alternative Splicing Amacrine Cells Biological Assay Biomedical Research Birth Cell Adhesion Molecules Cell Count Cell Death Cells Cellular Stress Chromosomes, Human, Pair 21 Code Communities Complex Coupled Cues Development Developmental Process Disease Down Syndrome Down Syndrome Cell Adhesion Molecule Drosophila genus Environment Etiology Eye Funding Genes Goals Homologous Gene Incidence Ligands Light Mediating Modeling Molecular Mus Mutant Strains Mice Mutation Nervous system structure Neurites Neurons Neurosciences Pathology Patients Pattern Phenotype Play Process Protein Isoforms Publishing RNA Splicing Regulation Reporting Research Research Proposals Retina Retinal Retinal Ganglion Cells Role Scientific Advances and Accomplishments Series Staging Stress Synapses System Testing Time Trisomy Universities Vertebrates Visual Washington Work axon guidance career cell type dosage gene function genetic resource light deprivation molecular recognition monocular mouse model mutant mouse model nervous system development neural patterning neurodevelopment neuron loss neuronal cell body overexpression prevent programs receptor relating to nervous system research study retinal rods

项目摘要

ABSTRACT: Candidate and Environment: Dr. Peter Fuerst will conduct the research contained within this proposal at Washington State University. Washington State University is an ideal environment in which to conduct advanced biomedical research using mouse models and in which to advance a research program. Research Proposal: The research we propose will use mouse models to identify the molecular mechanisms underpinning development of the retina. The mouse models, all developed by the applicant, include a conditional allele of the Down syndrome cell adhesion molecule, Dscam, as well as an allelic series of mouse mutant Dscam strains and a null allele of the Dscam homologue Dscam-like1 (Dscaml1). Dscam and Dscam- Like1 are essential for normal development of the nervous system and Dscam is proposed to contribute to the pathology of Down syndrome. In the retina, Dscam is required for soma mosaic spacing, regulation of cell number and neurite arborization and lamination. Our published results concerning Dscam and Dscaml1 are the first demonstrations of mutations found to ablate mosaic patterning and the first genes shown to mediate isoneuronal and heteroneuronal repulsion in vertebrates. Specific Aims: We propose to use the Dscam and Dscaml1 mutant mouse models to discover mechanisms underpinning development of the retina and to probe the function of Dscam in the mammalian nervous system. This will be accomplished by testing the following hypotheses detailed in this research proposal. Hypotheses: 1) We will test the hypothesis that DSCAM mediates multiple distinct functions using an allelic series and conditional allele of Dscam mouse mutant lines to genetically and temporally isolate Dscam-dependent developmental processes. 2) We will test the hypothesis that DSCAM mediates adhesion between cell types and repulsion within cell types and that DSCAM activity in the retina is mediated by homophillic interactions and not by a ligand-receptor mechanism by using a conditional allele coupled to cell type specific deletion. 3) We will test the hypothesis that Dscam and Dscaml1 regulate normal developmental cell death. Long-term goals: This research will uncover fundamental aspects of neural organization and provide the funding necessary for Dr. Fuerst to establish a successful academic career focused on hypothesis driven biomedical research. Significance: Neurite arborization, regulation of cell number and soma mosaic spacing are fundamental aspects of neurodevelopment that are not currently well understood at the molecular level in vertebrates. Our preliminary research indicates that DSCAM plays a vital role in mediating these processes in the mammalian nervous system. Identifying mechanisms by which DSCAM functions using a series of mouse mutant alleles and a conditional allele will contribute to our understanding of nervous system development and the causation of disorders associated with neural dysgenesis and also contribute valuable research models to the neuroscience community.

摘要：候选人与环境：彼得·富尔斯特博士将主持本研究