Regulation of FGF signaling in lacrimal gland development

FGF信号在泪腺发育中的调节

• 批准号: 8206828
• 负责人: Xin Zhang
• 金额: $ 29.27万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8206828
• 关键词: Affect; Alleles; Anabolism; Binding; Biochemical; Biological Assay; Cell surface; Cells; Chondroitin Sulfates; Clinical; Communication; Conjunctival Epithelium; Defect; Development; Diagnosis; Disease; Dry Eye Syndromes; Epithelial; Epithelium; Etiology; Extracellular Space; Eye Abnormalities; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Future; Genes; Genetic Models; Glycosaminoglycans; Goals; Heparin; Heparitin Sulfate; Human; Human Development; Inorganic Sulfates; Intervention; Knock-out; Lacrimal gland structure; Lead; Mediating; Medical Research; Mesenchymal; Mesenchyme; Modification; Molecular; Morphogenesis; Movement; Mus; Pathway interactions; Pattern; Process; Receptor Gene; Regulation; Role; Signal Pathway; Signal Transduction; Structure; Study models; System; Testing; Unspecified or Sulfate Ion Sulfates; Work; base; gland development; human disease; insight; lacrimal; mutant; polysulfated glycosaminoglycan; research study; response; sulfation

PROJECT SUMMARY The long term objective of this project is to investigate the regulation of FGF signaling in lacrimal gland development, which has important implications for understanding the etiology of the diseased lacrimal gland in human. The lacrimal gland develops through a branching morphogenesis process primarily driven by FGF signaling, which itself is regulated by glycosaminoglycan in the extracellular space. This application will focus on the role of glycosaminoglycan in lacrimal gland development and determine how the glycosaminoglycan fine structure regulates FGF signaling. Specifically, mouse genetic models will be developed to test the functions of glycosaminoglycan biosynthetic genes in lacrimal gland development, biochemical assays will be performed to examine the interaction between glycosaminoglycan and FGF molecules, and finally, explant culture systems will be utilized to determine the requirement of glycosaminoglycan in FGF signaling. By investigating the regulation of FGF signaling in murine lacrimal gland, this project will both contribute to medical research in treating human congenital eye diseases and advance our understanding of the mesenchymal-epithelial interaction paradigm.

项目摘要 本项目的长期目标是研究泪腺中FGF信号的调节 发育，这对于了解泪腺疾病的病因具有重要意义 人类泪腺通过主要由FGF驱动的分支形态发生过程发育 信号传导，其本身由细胞外空间中的糖胺聚糖调节。该应用程序将重点 糖胺聚糖在泪腺发育中的作用，并确定糖胺聚糖 精细结构调节FGF信号传导。具体来说，将开发小鼠遗传模型来测试 糖胺聚糖生物合成基因在泪腺发育中的功能，生化检测将 检查糖胺聚糖和FGF分子之间的相互作用，最后， 培养系统将用于确定FGF信号传导中糖胺聚糖的需求。通过 研究小鼠泪腺中FGF信号的调节，该项目将有助于 治疗人类先天性眼病的医学研究，并促进我们对 间质-上皮相互作用范例。