Lens ectoderm-derived Wnt signaling regulates eye development
Lens ectoderm-derived Wnt signaling regulates eye development
批准号:
10065127
负责人:
Xin Zhang
金额:
$36.45万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-07-01 至 2024-08-31
关键词:
AnatomyAniridiaAnteriorBiochemical GeneticsCell Culture TechniquesCorneaDataDevelopmentDevelopmental ProcessDiseaseDistalEctodermEyeEye DevelopmentFRAP1 geneFailureFibroblast Growth FactorFibroblast Growth Factor ReceptorsFutureGeneticGenetic EpistasisGenetic ModelsGenetic TranscriptionGoalsGrowthGrowth FactorHomeostasisHumanHuman DevelopmentInvestigationIrido-corneo-trabecular dysgenesisIrisKnock-outLeadLens developmentLigandsMediatingMessenger RNAModelingMolecularNF1 geneNaturePathway interactionsPatientsPatternPhysiologyPositioning AttributeProductionProtein BiosynthesisProteinsRegenerative MedicineRegulationRestRetinaRoleSignal PathwaySignal TransductionSignaling MoleculeSourceSurface EctodermTestingTissuesTo specifyTranslation InitiationVesicleVision researchVisual system structureWNT Signaling PathwayWnt proteinsbasebeta cateninbiological systemsexperimental studygenetic approachhuman diseaseinsightlensmTOR inhibitionmouse geneticsprogramsprotein expressionreceptortherapeutic development
中文摘要
项目总结
晶状体囊泡关闭失败导致晶状体和角膜的不完全分离,这是
彼得斯异常。睫状缘发育缺陷是无虹膜的基础,其特征是
患者的虹膜缺失。这些令人衰弱的先天性疾病强调了前部的重要性
细分市场发展。作为视觉系统的焦点,晶状体处于与人相互作用的良好位置
角膜在前部,视网膜在后部。尽管许多生长因素被牵连到
晶状体发育,这些因素如何相互作用来协调精确的发育计划仍然很差
明白了。因为这些信号分子也参与了许多人类疾病的其余部分
对这些信号通路的研究可能会带来更好的理解和治疗
眼科疾病。在这个项目中,我们将重点研究晶状体外胚层在发育过程中产生的Wnt配体的作用
眼睛发育。结合生化和遗传方法,我们将研究Wnt的调节
晶状体外胚层内的信号。此外,我们将研究WNT和成纤维细胞生长因子信号如何在
晶状体囊泡的闭合。最后,我们将研究晶状体外胚层衍生的Wnt配体是如何共同作用的
视网膜成纤维细胞生长因子信号形成远端视网膜的纤毛边缘。组织的信号调控
相互作用是生物系统发展和动态平衡的基础。我们对信令的研究
串扰可能会对视觉研究产生重大影响。
英文摘要
PROJECT SUMMARY
Failure of lens vesicle closure leads to an incomplete separation of the lens and cornea, a hallmark of the
Peters anomaly. Defective ciliary margin development underlies aniridia, which is characterized by the
absence of the iris in patients. These debilitating congenital diseases underscore the importance of anterior
segment development. As the focal point of the visual system, the lens is well position to interact with the
cornea in the anterior and the retina in the posterior. Although many growth factors have been implicated in
lens development, how these factors interact to orchestrate the precise developmental program is still poorly
understood. As these signaling molecules are also involved in numerous human diseases in the rest of the
eye, investigation of these signaling pathways could potentially lead to better understanding and treatment of
ocular diseases. In this project, we will focus on the role of Wnt ligands produced by the lens ectoderm during
eye development. Combining biochemical and genetic approaches, we will investigate the regulation of Wnt
signaling within the lens ectoderm. Furthermore, we will examine how Wnt and FGF signaling interacts during
the closure of the lens vesicle. Finally, we will investigate how lens ectoderm-derived Wnt ligands act together
with the retinal FGF signaling to pattern the ciliary margin in the distal retina. Signaling control of tissue
interactions is fundamental to development and homeostasis of biological systems. Our study of signaling
crosstalk may have significant impact beyond the vision research.
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会议论文
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