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.

项目概要 晶状体囊泡闭合失败导致晶状体和角膜不完全分离，这是晶状体的一个标志 彼得斯异常。睫状体边缘发育缺陷是无虹膜的基础，其特征是 患者虹膜缺失。这些使人衰弱的先天性疾病强调了前路的重要性 细分市场发展。作为视觉系统的焦点，晶状体处于与物体相互作用的良好位置。 角膜在前部，视网膜在后部。尽管许多生长因子都与 在晶状体发育过程中，这些因素如何相互作用以协调精确的发育计划仍然很差 明白了。由于这些信号分子也与其他领域的许多人类疾病有关 眼睛，对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，我们将重点研究晶状体外胚层产生的Wnt配体在晶状体发育过程中的作用。 眼睛发育。结合生化和遗传学方法，我们将研究Wnt的调控 晶状体外胚层内的信号传导。此外，我们将研究 Wnt 和 FGF 信号在 晶状体囊泡的关闭。最后，我们将研究晶状体外胚层来源的 Wnt 配体如何共同作用 视网膜 FGF 信号传导使远端视网膜的睫状缘图案化。组织的信号控制 相互作用是生物系统发展和稳态的基础。我们对信号传导的研究 串扰可能对视觉研究之外产生重大影响。