Genetic Analysis of Dendrite and Dendritic Filopodia Formation

树突和树突丝状伪足形成的遗传分析

基本信息

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
项目类别：
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

项目摘要

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，大多数信息处理在物理上发生在神经元树突上。了解树突和树突结构如何发展和功能对于理解正常认知以及人类认知障碍和延迟综合症可能受到干扰至关重要。在阿尔茨海默氏症，脆弱的X和Downs综合征中存在树突状形态改变的证据。在某些脊椎动物中，有证据表明树突状丝霉菌有助于形成树突状乔木。在哺乳动物中，至少有一些树突状丝状可以成为树突状刺。在果蝇中，我们能够在光学透明的完整动物中可视化树突和树突状丝状。我们认为，使用简单但强大的遗传模型对树突和树突状丝霉菌发育进行研究，应产生对更复杂的哺乳动物树突发育的见解。我们的方法结合了一种遗传性的生物果蝇，与高分辨率显微镜进行大规模正向遗传学，以鉴定调节树突状发育的基因和信号通路。我们还研究了Camkii的作用，Camkii是与学习和记忆有关的分子，是果蝇中树突状结构的有效调节剂。由于在果蝇中发现了所有人类神经疾病基因中的72％，因此本文确定的此类基因的直系同源物可能是候选者在哺乳动物树突发育中发挥作用和潜在的人类疾病。