Pros/Prox1 and Lens Development
Pros/Prox1 和镜头开发
基本信息
- 批准号:7494953
- 负责人:
- 金额:$ 33.08万
- 依托单位:
- 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:2007-09-15 至 2012-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnteriorBiochemicalBiological AssayBlindnessCataractCell Differentiation processCellsCrystallinsCultured CellsCytoplasmDNA BindingDataDefectDepthDevelopmentDiseaseDrosophila eyeDrosophila genusEmbryoEventExhibitsEyeEye DevelopmentFailureFamilyFoundationsFutureGene ExpressionGene TargetingGeneticGenetic ModelsIn VitroInvertebratesKnock-outLeadLens FiberMediatingModelingMolecularMusNuclearOrthologous GenePathway interactionsPatientsPatternPhenotypePlayPregnancyProcessProteinsRegulationRegulatory PathwayReporterReportingResearch PersonnelRetinal ConeRoleSite-Directed MutagenesisSpecificityStagingStructureStudy modelsTestingVertebratesWorkage relatedanterior chamberbasecongenital cataractcookingdayfiber cellflygenetic analysisin vivoknockout animallensmutantpreventprogramsprotein functionprotein protein interactionresearch studyretinogenesistranscription factor
项目摘要
DESCRIPTION (provided by applicant): In vertebrates, a functional lens requires the ability of lens fiber cells to differentiate, elongate, and express abundant levels of the appropriate crystallin molecules. Factors which affect any of these processes are detrimental and can lead to the formation of cataract disease. Knockout studies have shown that the mouse transcription factor Proxl regulates lens fiber elongation and crystallin gene expression. Unfortunately, Proxl knockout animals die by embryonic day 13.5, making further analysis of this phenotype difficult. Our preliminary data demonstrate that the Drosophila ortholog of Proxl, called Prospero (Pros), is also necessary for lens formation. Similar to Proxl, Pros affects lens cell differentiation and crystallin gene expression. This is one of the first reports that lens development in invertebrates and vertebrates shares similar transcriptional regulatory pathways. Interestingly, Pros and Proxl also exhibit both nuclear and cytoplasmic expression during lens cell differentiation, suggesting a non-transcriptional role for these proteins as well. The studies outlined here are aimed to explore the evolutionary conserved basis for Pros/Prox1-mediated lens development. For this, we will: 1) more precisely characterize the role for Pros in lens cell development, 2) test the contribution of Pros intracellular localization in lens development, and 3) characterize functional conservation with the Pros/Prox1 family of transcription factors. These studies will use a combination of in vitro biochemical and transcriptional regulatory assays, site-directed mutagenesis, and in vivo genetic analyses to provide a broad perspective on how Pros/Prox1 proteins function during lens development. This work will provide the framework necessary to perform more in-depth genetic studies aimed at identifying key regulatory pathways necessary for normal lens development as a means for understanding what aspects of these pathways are disturbed in patients suffering from congenital and age- related cataracts. LAY: Cataracts result from the failure of our lens to properly develop or to be maintained. Unfortunately, not much is known about how a normal lens develops, making it difficult for us to devise ways to prevent abnormal lens formation such as in cataract disease. This proposal is focused on developing a new genetic model that will allow us to rapidly identify new pathways that are necessary for lens development as a means to circumvent events that lead to cataract formation and blindness.
描述(由申请人提供):在脊椎动物中,功能性透镜需要透镜纤维细胞分化、伸长和表达丰富水平的适当晶状体蛋白分子的能力。影响这些过程中的任何一个的因素都是有害的,并且可以导致白内障疾病的形成。敲除研究表明,小鼠转录因子Proxl调节透镜纤维的伸长和晶状体蛋白基因的表达。不幸的是,Proxl基因敲除的动物在胚胎第13.5天死亡,使得对这种表型的进一步分析变得困难。我们的初步数据表明,果蝇直系同源的Proxl,称为普洛斯彼罗(优点),也是必要的透镜的形成。与Proxl类似,Pros影响透镜细胞分化和晶状体蛋白基因表达。这是第一个报告,透镜发展在无脊椎动物和脊椎动物共享类似的转录调控途径。有趣的是,Pros和Proxl在透镜细胞分化过程中也表现出核和胞质表达,表明这些蛋白质也具有非转录作用。本文旨在探讨Pros/Prox 1介导的透镜发育的进化保守基础。为此,我们将:1)更精确地表征Pros在透镜细胞发育中的作用,2)测试Pros细胞内定位在透镜发育中的贡献,以及3)表征转录因子的Pros/Prox 1家族的功能保守性。这些研究将使用体外生物化学和转录调控分析,定点诱变,并在体内遗传分析的组合,以提供一个广泛的观点如何在透镜发展过程中的Pros/Prox 1蛋白的功能。这项工作将提供必要的框架,以进行更深入的遗传研究,旨在确定正常透镜发育所需的关键调控途径,作为了解患有先天性和年龄相关性白内障的患者中这些途径的哪些方面受到干扰的手段。白内障是由于我们的透镜不能正常发育或维持而引起的。不幸的是,对正常透镜如何发育的了解不多,使得我们难以设计出防止异常透镜形成(例如白内障疾病)的方法。该提案的重点是开发一种新的遗传模型,使我们能够快速识别透镜发育所必需的新途径,作为规避导致白内障形成和失明的事件的手段。
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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Tiffany Cook其他文献
Tiffany Cook的其他文献
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{{ truncateString('Tiffany Cook', 18)}}的其他基金
Molecular Networks Controlling Subtype Specification of Color Photoreceptors
控制彩色感光器亚型规范的分子网络
- 批准号:
9096819 - 财政年份:2015
- 资助金额:
$ 33.08万 - 项目类别:
Molecular Networks Controlling Subtype Specification of Color Photoreceptors
控制彩色感光器亚型规范的分子网络
- 批准号:
8759229 - 财政年份:2014
- 资助金额:
$ 33.08万 - 项目类别:
Defining Glial Programs that Support Adult Photoreceptor Form and Function
定义支持成体感光器形式和功能的神经胶质程序
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8681648 - 财政年份:2014
- 资助金额:
$ 33.08万 - 项目类别:
REGULATION OF RHODOPSIN GENE EXPRESSION IN DROSOPHILA
果蝇视紫红质基因表达的调控
- 批准号:
6518393 - 财政年份:2002
- 资助金额:
$ 33.08万 - 项目类别:
REGULATION OF RHODOPSIN GENE EXPRESSION IN DROSOPHILA
果蝇视紫红质基因表达的调控
- 批准号:
6397749 - 财政年份:2001
- 资助金额:
$ 33.08万 - 项目类别:
REGULATION OF RHODOPSIN GENE EXPRESSION IN DROSOPHILA
果蝇视紫红质基因表达的调控
- 批准号:
6143554 - 财政年份:2000
- 资助金额:
$ 33.08万 - 项目类别:
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