Retinal Epithelial Polarity and Cellular Patterning
视网膜上皮极性和细胞图案
基本信息
- 批准号:7487320
- 负责人:
- 金额:$ 30.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-09-30 至 2010-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAffinity ChromatographyArchitectureBiochemicalBiologicalCandidate Disease GeneCell PolarityCellsComplexCuesDataDefectDevelopmentDiseaseEmbryoEngineeringEnsureEpithelialEpithelial CellsEpitheliumEyeFishesGenesGeneticInvertebratesLinkMethodsMolecularMorphogenesisNeural RetinaNumbersOrganPatternPattern FormationPlayProtein Binding DomainProtein IsoformsProteinsResearchResearch PersonnelRetinaRetinalRetinal DegenerationRoleSeriesSet proteinStagingStructureStructure of retinal pigment epitheliumSystemTertiary Protein StructureTestingTissuesTransgenic OrganismsYeastsZebrafishcell motilityinterestknock-downloss of functionprogramsprotein protein interactionrelating to nervous systemyeast two hybrid system
项目摘要
DESCRIPTION (provided by applicant): Retinal engineering is likely to be the ultimate cure for blinding disorders caused by degeneration of retinal cells. A prerequisite for retinal engineering is understanding the mechanisms of cellular pattern formation in the vertebrate retina. Our long-term research interest is to define these mechanisms. Recent studies suggest that the polarity of the retinal epithelia plays an essential role in neural retinal pattern formation; but the mechanisms involved are largely unknown. We have shown that three zebrafish polarity genes (nok, Pard3, and zLinT) are required to establish the cellular architecture of the mature retina. These proteins all contain well-established protein-protein interaction domains. Our data suggest that zLin7 likely interacts with Nok and that Nok is required for the interactions between the neural retina and the juxtaposed retinal pigmented epithelium (RPE). Our central hypothesis is that Nok, Pard3, and zLin7 associate with other proteins in a developmentally regulated fashion to collectively establish and/or maintain the proper polarity of retinal epithelia and consequently ensure accurate interactions between the neural retina and RPE. These interactions likely enable the proper distribution of cell migration cues required for retinal pattern formation. The major aims of the research to be pursued in this project include: 1) Determine to what extent Nok's function in controlling cellular pattern formation in the neural retina requires Nok's activity in the RPE by making and analyzing transgenic embryos that display mosaic Nok expressions in the eye; 2) Determine whether Nok physically interacts with one or more isoforms of zLin7's and what protein domains are involved in the interaction; 3) Identify and characterize the proteins that interact with Nok, Pard3, and zLin7 complexes during retinal development by using affinity purification, yeast two-hybrid, and candidate genes approaches.
描述(由申请人提供):视网膜工程可能是治疗由视网膜细胞退化引起的失明疾病的最终疗法。视网膜工程的先决条件是了解脊椎动物视网膜中细胞模式形成的机制。我们的长期研究兴趣是定义这些机制。最近的研究表明,视网膜上皮细胞的极性在神经视网膜模式的形成中起着至关重要的作用。但所涉及的机制在很大程度上尚不清楚。我们已经证明,建立成熟视网膜的细胞结构需要三个斑马鱼极性基因(nok、Pard3 和 zLinT)。这些蛋白质都含有完善的蛋白质-蛋白质相互作用结构域。我们的数据表明,zLin7 可能与 Nok 相互作用,并且 Nok 是神经视网膜和并置的视网膜色素上皮 (RPE) 之间相互作用所必需的。我们的中心假设是,Nok、Pard3 和 zLin7 以发育调节的方式与其他蛋白质结合,共同建立和/或维持视网膜上皮细胞的正确极性,从而确保神经视网膜和 RPE 之间的准确相互作用。这些相互作用可能使得视网膜图案形成所需的细胞迁移线索能够正确分布。该项目的研究主要目标包括: 1) 通过制作和分析在眼睛中显示马赛克 Nok 表达的转基因胚胎,确定 Nok 控制神经视网膜细胞模式形成的功能在多大程度上需要 RPE 中的 Nok 活性; 2) 确定 Nok 是否与 zLin7 的一种或多种亚型发生物理相互作用,以及哪些蛋白质结构域参与相互作用; 3) 通过使用亲和纯化、酵母双杂交和候选基因方法,鉴定和表征视网膜发育过程中与 Nok、Pard3 和 zLin7 复合物相互作用的蛋白质。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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XIANGYUN WEI其他文献
XIANGYUN WEI的其他文献
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{{ truncateString('XIANGYUN WEI', 18)}}的其他基金
Crumbs proteins for photoreceptor development and health maintenance
用于光感受器发育和健康维护的碎屑蛋白质
- 批准号:
9105969 - 财政年份:2016
- 资助金额:
$ 30.95万 - 项目类别:
Regulating retinal gene expression in three-dimensional nuclear space
调控三维核空间中的视网膜基因表达
- 批准号:
8699920 - 财政年份:2014
- 资助金额:
$ 30.95万 - 项目类别:
Retinal Epithelial Polarity and Cellular Patterning:Crbs and their associates
视网膜上皮极性和细胞模式:Crbs 及其同事
- 批准号:
8323479 - 财政年份:2005
- 资助金额:
$ 30.95万 - 项目类别:
Retinal Epithelial Polarity and Cellular Patterning
视网膜上皮极性和细胞图案
- 批准号:
7676686 - 财政年份:2005
- 资助金额:
$ 30.95万 - 项目类别:
Retinal Epithelial Polarity and Cellular Patterning:Crbs and their associates
视网膜上皮极性和细胞模式:Crbs 及其同事
- 批准号:
7984472 - 财政年份:2005
- 资助金额:
$ 30.95万 - 项目类别:
Retinal Epithelial Polarity and Cellular Patterning
视网膜上皮极性和细胞图案
- 批准号:
6969518 - 财政年份:2005
- 资助金额:
$ 30.95万 - 项目类别:
Retinal Epithelial Polarity and Cellular Patterning
视网膜上皮极性和细胞图案
- 批准号:
7281182 - 财政年份:2005
- 资助金额:
$ 30.95万 - 项目类别:
Retinal Epithelial Polarity and Cellular Patterning:Crbs and their associates
视网膜上皮极性和细胞模式:Crbs 及其同事
- 批准号:
8126300 - 财政年份:2005
- 资助金额:
$ 30.95万 - 项目类别:
Retinal Epithelial Polarity and Cellular Patterning
视网膜上皮极性和细胞图案
- 批准号:
7123831 - 财政年份:2005
- 资助金额:
$ 30.95万 - 项目类别:
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