Regulation of FGF signaling in lacrimal gland development

项目总结 该项目的长期目标是研究泪腺中成纤维细胞生长因子信号的调节。 泪腺病变的发生发展，对了解儿童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。 我们先前已经证明，Ras-MAPK通路是成纤维细胞生长因子信号转导的重要下游靶点。 泪腺形态发生。在本应用程序中，我们将测试PLCγ也是关键的假设 泪腺发育过程中成纤维细胞生长因子信号的调节。利用条件突变小鼠和细胞培养 模型，我们将研究成纤维细胞生长因子受体如何募集和激活PLCγ。我们还将检查串扰 泪腺发育中PLC、γ和RAS信号之间的关系。最后，我们将检验PLCγ的假设 通过控制成纤维细胞生长因子受体的内吞作用来调节成纤维细胞生长因子信号的强度。通过调查 小鼠泪腺成纤维细胞生长因子信号的调控，本项目将为治疗的医学研究提供帮助 人类泪腺缺乏症与干眼症。

PROJECT SUMMARY The long term objective of this project is to investigate regulation of FGF signaling in lacrimal gland development, which has important implications for understanding the etiology of diseased lacrimal gland in human. The lacrimal gland develops through a branching morphogenesis process primarily driven by FGF. We have previously shown that the Ras-MAPK pathway is an important downstream target of FGF signaling in lacrimal gland morphogenesis. In this application, we will test the hypothesis that PLCγ is also a critical regulator of FGF signaling in lacrimal gland development. Using conditional mutant mice and cell culture models, we will study how FGF receptor recruits and activates PLCγ. We will also examine the crosstalk between PLCγ and Ras signaling in lacrimal gland development. Finally, we will test the hypothesis that PLCγ modulates the strength of FGF signaling by controlling endocytosis of FGF receptor. By investigating the regulation of FGF signaling in murine lacrimal gland, this project will contribute to medical research in treating human lacrimal gland deficiency and the dry eye disease.