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.

项目总结 该项目的长期目标是研究成纤维细胞生长因子信号在泪腺中的调节。 泪腺病变的发生发展，对了解泪腺病变的病因具有重要意义。 人类。泪腺的发育主要是由成纤维细胞生长因子驱动的分枝形态发生过程。 信号，这本身是由细胞外空间的糖胺聚糖调节的。此应用程序将专注于 糖胺多聚糖在泪腺发育中的作用及其测定 精细结构调控成纤维细胞生长因子信号转导。具体地说，将开发老鼠遗传模型来测试 糖胺多聚糖生物合成基因在泪腺发育中的作用，生化分析将是 用来检测糖胺聚糖和成纤维细胞生长因子分子之间的相互作用，最后，外植体 培养系统将被用来确定糖胺聚糖在成纤维细胞生长因子信号转导中的需求。通过 研究成纤维细胞生长因子信号在小鼠泪腺中的调节，这一项目将有助于 在治疗人类先天性眼病方面的医学研究，提高对先天性眼病的认识 间充质-上皮相互作用范式。