Regulation of FGF signaling in lacrimal gland development

项目摘要 本项目的长期目标是研究泪腺中FGF信号的调节 发展，这对了解疾病泪腺的病因学有重要意义， 人类泪腺通过主要由FGF驱动的分支形态发生过程发育。 我们先前已经表明，Ras-MAPK途径是FGF信号传导的重要下游靶点， 泪腺形态发生在本申请中，我们将检验PLCγ也是一个关键因素的假设。 泪腺发育中FGF信号的调节剂。使用条件突变小鼠和细胞培养 模型中，我们将研究FGF受体如何募集和激活PLCγ。我们还将研究串扰 PLCγ和Ras信号在泪腺发育中的作用最后，我们将检验PLCγ 通过控制FGF受体的内吞作用调节FGF信号传导的强度。通过调查 调节小鼠泪腺中FGF信号传导，该项目将有助于治疗方面的医学研究 人类泪腺缺乏症和干眼症。

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.