The Role of Planar Cell Polarity Signals in Shaping Kidney Tubules
平面细胞极性信号在肾小管塑造中的作用
基本信息
- 批准号:8508258
- 负责人:
- 金额:$ 11.35万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-09-01 至 2017-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAmphibiaAnimalsArchitectureCell PolarityCell divisionCellsCiliaCystic Kidney DiseasesDataDefectDevelopmentDiseaseDockingEmbryoEpithelialEpitheliumEquilibriumExperimental ModelsGoalsHumanImageImageryKidneyKidney DiseasesKnowledgeLeadLifeLinkMaintenanceMalignant NeoplasmsMammalsMediatingMesenchymeMethodsModelingMolecular TargetMonomeric GTP-Binding ProteinsMorphogenesisNational Institute of Diabetes and Digestive and Kidney DiseasesNephroblastomaNephronophthisisNephronsOrganOutcomePathogenesisPathologyPathway interactionsPhysical condensationPlayPolycystic Kidney DiseasesProcessPublicationsPublishingRanaRegulationRenal Cell CarcinomaRenal carcinomaRenal tubule structureResearch Project GrantsResearch SupportRoleShapesSignal PathwaySignal TransductionStrabismusSumSurface EctodermSystemTechniquesTestingTissuesTransgenic AnimalsTransgenic OrganismsTubeVisionWorkXenopusXenopus laevisZebrafishbasebeta catenincell motilitycilium biogenesisdirectional cellinnovationinsightkinetosomeneoplastic cellnephrogenesisnovelresearch study
项目摘要
DESCRIPTION (provided by applicant): Formation of renal tubules in both mammals and amphibians requires Wnt pathways. In kidney, aberrant Wnt signaling has been linked to developmental pathologies such as Wilms tumor and cystic diseases, as well as with renal cell carcinoma. Recent studies from our group and others indicate that canonical (?-catenin- mediated) Wnt signaling is essential for induction of nephron development. Additionally, studies suggest that primary cilia are required for a switch from canonical to non-canonical Wnt signaling, and that defects in primary cilia formation or signaling lead to cystogenesis. Varied tissues undergoing morphogenesis employ non-canonical Wnt (PCP: "planar cell polarity") pathways to promote processes including cell polarization and cytoskeletal modulation. Deficiencies in non-canonical Wnt signaling, which contributes to PCP, underlie a number of developmental or later defects, such as polycystic kidney disease and nephronophthisis. Using Xenopus laevis (frog) embryos, supplemented in some contexts with embryos of Danio rerio (zebrafish), this proposal first assesses the roles of non-canonical Wnt PCP components in kidney tubule morphogenesis. Our hypothesis is that the PCP components Daam1, WGEF, Prickle and Strabismus are required for primary cilia formation, which is in turn required for nephric morphogenesis. Xenopus offers experimental advantages including the facile introduction of exogenous constructs to block or activate signaling pathways, rapid development and easy visualization of the forming kidney under the surface ectoderm. Second, using transgenic approaches, we will address in living animals the role of PCP/ non-canonical Wnt signals in shaping and moving cells that are undergoing/ contributing to kidney tubule morphogenesis. Finally, an over-expression screen will be performed to discover new regulators of tubule formation. Overall, this work is novel in assessing the roles of the PCP components in kidney development; in utilizing transgenic approaches in Xenopus laevis to visualize and/ or target kidney development in living embryos; and in performing an unbiased over- expression screen to reveal additional and likely novel components involved in kidney tubulogenesis. In sum, we will enhance our understanding of kidney morphogenesis, which is likely to be relevant to obtaining insights on later pathologies that arise in humans.
描述(由申请人提供):哺乳动物和两栖动物中肾小管的形成需要Wnt途径。在肾脏中,异常Wnt信号传导与发育病理学如肾母细胞瘤和囊性疾病以及肾细胞癌有关。我们小组和其他人最近的研究表明,典型的(?-连环蛋白介导的)Wnt信号传导对于诱导肾单位发育是必需的。此外,研究表明,初级纤毛是从经典到非经典Wnt信号传导的转换所必需的,并且初级纤毛形成或信号传导的缺陷导致囊肿发生。经历形态发生的各种组织采用非经典Wnt(PCP:“平面细胞极性”)途径来促进包括细胞极化和细胞骨架调节的过程。导致PCP的非经典Wnt信号转导缺陷是许多发育或后期缺陷的基础,如多囊肾病和肾单位营养不良。使用非洲爪蟾(青蛙)的胚胎,补充在某些情况下与斑马鱼(斑马鱼)的胚胎,该建议首先评估非典型的Wnt PCP组件在肾小管形态发生的作用。我们的假设是,PCP组件Daam 1,WGEF,刺痛和斜视所需的初级纤毛的形成,这反过来又需要肾形态发生。非洲爪蟾提供了实验优势,包括容易引入外源性结构来阻断或激活信号通路,快速发育和容易观察表面外胚层下形成的肾脏。其次,使用转基因方法,我们将在活体动物中解决PCP/非经典Wnt信号在塑造和移动正在经历/有助于肾小管形态发生的细胞中的作用。最后,将进行过表达筛选以发现新的小管形成调节剂。总体而言,这项工作在以下方面是新颖的:评估PCP组分在肾脏发育中的作用;在非洲爪蟾中利用转基因方法来可视化和/或靶向活胚胎中的肾脏发育;以及进行无偏倚的过表达筛选以揭示参与肾小管发生的额外的和可能的新组分。总之,我们将提高我们对肾脏形态发生的理解,这可能与获得人类后期病理学的见解有关。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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Rachel Katherine Miller其他文献
Rachel Katherine Miller的其他文献
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{{ truncateString('Rachel Katherine Miller', 18)}}的其他基金
Diversity Supplement: Novel Role of Nephron Epithelialization in Nuclear Signaling
多样性补充:肾单位上皮化在核信号传导中的新作用
- 批准号:
10853534 - 财政年份:2023
- 资助金额:
$ 11.35万 - 项目类别:
Novel Role of Nephron Epithelialization in Nuclear Signaling
肾单位上皮化在核信号传导中的新作用
- 批准号:
10587605 - 财政年份:2019
- 资助金额:
$ 11.35万 - 项目类别:
Role of p53 in Kidney Development: Modeling Renal Anomalies of Li-Fraumeni Patients
p53 在肾脏发育中的作用:Li-Fraumeni 患者肾脏异常建模
- 批准号:
9765314 - 财政年份:2018
- 资助金额:
$ 11.35万 - 项目类别:
The Role of Planar Cell Polarity Signals in Shaping Kidney Tubules
平面细胞极性信号在肾小管塑造中的作用
- 批准号:
8383143 - 财政年份:2012
- 资助金额:
$ 11.35万 - 项目类别:
The Role of Planar Cell Polarity Signals in Shaping Kidney Tubules
平面细胞极性信号在肾小管塑造中的作用
- 批准号:
8734953 - 财政年份:2012
- 资助金额:
$ 11.35万 - 项目类别:
Non-canonical Wnt Signals in Kidney Tubulogenesis
肾小管发生中的非典型 Wnt 信号
- 批准号:
7669089 - 财政年份:2008
- 资助金额:
$ 11.35万 - 项目类别:
Non-canonical Wnt Signals in Kidney Tubulogenesis
肾小管发生中的非典型 Wnt 信号
- 批准号:
7545595 - 财政年份:2008
- 资助金额:
$ 11.35万 - 项目类别:
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