Genetic Analysis of Dendrite and Dendritic Filopodia Formation

树突和树突丝状伪足形成的遗传分析

• 批准号: 7337255
• 负责人: JAY BRENMAN
• 金额: $ 5.04万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7337255
• 关键词: Actin-Binding Protein; Actins; Affinity; Alleles; Animals; Axon; Biological; Brain; Bulla; Cell Polarity; Cells; Chromosome Mapping; Class; Cognition; Cognition Disorders; Complex; Computer information processing; Consensus; Cytoskeleton; Data; Defect; Dendrites; Dendritic Spines; Development; Direct Repeats; Disease; Dominant-Negative Mutation; Down Syndrome; Drosophila genus; Event; F-Actin; Filopodia; Fragile X Syndrome; Genes; Genetic; Genetic Models; Genetic Structures; Genetic screening method; Glycogen Synthase Kinase 3; Hand; Human; Image; Length; Lesion; Life; Link; Localized; Mammals; Maps; Microscopy; Microtubule-Associated Proteins; Microtubules; Molecular; Morphogenesis; Morphology; Mutation; Neurons; Numbers; Organism; Pathway interactions; Phenocopy; Phenotype; Phosphorylation; Phosphorylation Site; Phosphotransferases; Play; Protein-Serine-Threonine Kinases; Proteins; Reagent; Regulation; Relative (related person); Research Personnel; Resolution; Role; Serum; Shapes; Signal Transduction; Signaling Molecule; Stretching; Structure; Syndrome; System; Temperature; Testing; Thinking; Transgenes; Transgenic Animals; Vertebrates; cell type; genetic analysis; genetic regulatory protein; in vivo; insight; loss of function; microtubule-associated protein 1B; mutant; nervous system disorder; polymerization; polyproline; profilin; programs; research study

DESCRIPTION (provided by applicant): In the brain, most information processing physically occurs on neuronal dendrites. Understanding how dendrites and dendritic structure develop and function is critical to understanding normal cognition and what may be perturbed in human cognitive disorders and retardation syndromes. Evidence for altered dendritic morphology exists in Alzheimers, Fragile X, and Downs syndrome. In some vertebrates there is evidence that dendritic filopodia help form dendritic arbors. In mammals, at least some dendritic filopodia can become dendritic spines. In Drosophila, we are able to visualize dendrites and dendritic filopodia in optically transparent intact animals. We believe the study of dendrites and dendritic filopodia development using a simple but powerful genetic model, should yield insights into more complex mammalian dendrite development. Our approach combines a genetically amenable organism, Drosophila, with high-resolution microscopy to perform large-scale forward genetics to identify genes and signaling pathways regulating dendritic development. We are also investigating the roles of CaMKII, a molecule implicated in learning and memory, as a potent regulator of dendritic structure in Drosophila. As 72% of all human neurological disease genes are found in Drosophila, orthologues of such genes identified herein may be candidates to play a role in mammalian dendrite development and potentially human disease.

描述(由申请人提供)： 在大脑中，大多数信息的物理处理都发生在神经元树突上。了解树突和树突结构是如何发展和功能的，对于理解正常认知以及人类认知障碍和发育迟缓综合征中可能受到的干扰是至关重要的。阿尔茨海默病、脆性X综合征和唐斯综合征中存在树突状细胞形态改变的证据。在一些脊椎动物中，有证据表明树状丝状足有助于形成树状乔木。在哺乳动物中，至少有一些树状丝状足细胞可以变成树枝状刺。在果蝇中，我们能够在光学透明的完好动物身上看到树突和树突丝状足。我们相信，使用一个简单但强大的遗传模型来研究树突和树突丝状足的发育，应该会对更复杂的哺乳动物树突发育产生深刻的见解。我们的方法结合了遗传上可服从的有机体--果蝇，与高分辨率显微镜相结合，进行大规模的正向遗传学，以识别调节树突发育的基因和信号通路。我们还在研究CaMKII，一个与学习和记忆有关的分子，作为果蝇树突状结构的有效调节因子。由于72%的人类神经系统疾病基因是在果蝇中发现的，因此这些基因的同源基因可能在哺乳动物树突发育和潜在的人类疾病中发挥作用。