Regulation of FGF signaling in lacrimal gland development

描述(申请人提供)：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发育中的调控，这对了解人类泪腺疾病的病因具有重要意义。泪腺的发育主要是由成纤维细胞生长因子信号驱动的分枝形态发生过程，而成纤维细胞生长因子信号本身又受细胞外间隙中的糖胺聚糖的调节。这一应用将集中在糖胺多聚糖在泪腺发育中的作用，并确定糖胺多聚糖的精细结构如何调节成纤维细胞生长因子信号。具体地说，将建立小鼠遗传模型以测试糖胺多聚糖生物合成基因在泪腺发育中的功能，将进行生化分析以研究糖胺多聚糖与成纤维细胞生长因子分子之间的相互作用，最后将利用外植体培养系统来确定糖胺多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控，本项目将有助于治疗人类先天性眼病的医学研究，并促进我们对间充质-上皮相互作用范式的理解。公共卫生相关性本项目研究了成纤维细胞生长因子信号在泪腺发育中的作用机制。希望有助于我们理解人类发育和疾病的这一重要途径，并为未来干眼综合征临床干预的发展提供信息。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE This project investigates the mechanism of FGF signaling in lacrimal gland development. It is expected to contribute to our understanding of this important pathway in human development and disease, and inform future development of clinical interventions to treat dry eye syndrome.