Regulation of FGF signaling in lacrimal gland development

项目描述（由申请人提供）：本项目的长期目标是研究FGF信号在泪腺发育中的调节，这对理解人类泪腺疾病的病因具有重要意义。泪腺通过主要由FGF信号传导驱动的分支形态发生过程发育，FGF信号传导本身由细胞外间隙中的糖胺聚糖调节。本申请将集中在糖胺聚糖在泪腺发育中的作用，并确定糖胺聚糖的精细结构如何调节FGF信号传导。具体而言，将开发小鼠遗传模型以测试糖胺聚糖生物合成基因在泪腺发育中的功能，将进行生化测定以检查糖胺聚糖和FGF分子之间的相互作用，最后，将利用外植体培养系统来确定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，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-上皮相互作用模式的理解。公共卫生相关性本项目研究FGF信号传导在泪腺发育中的机制。预计这将有助于我们了解人类发育和疾病中的这一重要途径，并为未来治疗干眼综合征的临床干预措施的发展提供信息。

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.