Lens ectoderm-derived Wnt signaling regulates eye development

晶状体外胚层衍生的 Wnt 信号调节眼睛发育

• 批准号: 10259754
• 负责人: Xin Zhang
• 金额: $ 35.36万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259754
• 关键词: Anatomy; Aniridia; Anterior; Biochemical Genetics; Cell Culture Techniques; Cornea; Data; Development; Developmental Process; Disease; Distal; Ectoderm; Eye; Eye Development; FRAP1 gene; Failure; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Future; Genetic; Genetic Epistasis; Genetic Models; Genetic Transcription; Goals; Growth; Growth Factor; Homeostasis; Human; Human Development; Investigation; Irido-corneo-trabecular dysgenesis; Iris; Knock-out; Lead; Lens development; Ligands; Mediating; Messenger RNA; Modeling; Molecular; NF1 gene; Nature; Pathway interactions; Patients; Pattern; Physiology; Positioning Attribute; Production; Protein Biosynthesis; Proteins; Regenerative Medicine; Regulation; Rest; Retina; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Source; Surface Ectoderm; Testing; Tissues; To specify; Translation Initiation; Vesicle; Vision research; Visual system structure; WNT Signaling Pathway; Wnt proteins; base; beta catenin; biological systems; experimental study; genetic approach; human disease; insight; lens; mTOR inhibition; mouse genetics; programs; protein expression; receptor; regenerative treatment; therapeutic development

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.

项目总结