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: 10065127
• 负责人: Xin Zhang
• 金额: $ 36.45万
• 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/10065127
• 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; 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.

项目摘要 透镜囊泡闭合的失败导致透镜和角膜的不完全分离，这是晶状体囊泡闭合的标志。 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。这些使人衰弱的先天性疾病强调了前牙的重要性。 细分发展。作为视觉系统的焦点，透镜的位置很好地与 角膜在前部视网膜在后部。尽管许多生长因子与 透镜的发展，这些因素如何相互作用，以协调精确的发展计划仍然很差 明白由于这些信号分子也参与了许多人类疾病的其余部分， 这些信号通路的研究可能会导致更好地理解和治疗 眼部疾病在这个项目中，我们将重点关注透镜外胚层产生的Wnt配体在晶状体形成过程中的作用。 眼睛发育结合生物化学和遗传学方法，我们将研究Wnt的调控 在透镜外胚层内发出信号。此外，我们还将研究Wnt和FGF信号在细胞周期中如何相互作用。 透镜囊泡的闭合。最后，我们将研究透镜外胚层衍生的Wnt配体如何共同作用 与视网膜FGF信号传导一起形成远端视网膜中的睫状缘。组织信号控制 相互作用对于生物系统的发育和体内平衡是基本的。我们对信号的研究 串扰可能具有超出视觉研究的显著影响。