Regulation of FGF signaling in lacrimal gland development

FGF信号在泪腺发育中的调节

基本信息

批准号：
10477997
负责人：
Xin Zhang
金额：
$ 39.29万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10477997
关键词：
Ablation Affect Cell Culture Techniques Cell Proliferation Cell surface Cells Complement Conjunctival Epithelium Defect Diagnosis Disease Docking Dry Eye Syndromes Duct (organ) structure Endocytosis Etiology Feedback Fibroblast Growth Factor Fibroblast Growth Factor Receptors Future Genetic Genetic Models Goals Growth Human Human Development In Vitro Individual Intercept Intervention Lacrimal gland structure Lead Ligands MAP Kinase Gene Mediating Medical Research Mesenchyme Modeling Molecular Morphogenesis Mus Mutant Strains Mice Mutate PLC gamma1 Pathway interactions Pattern Persons Phenotype Physiology Process Regenerative Medicine Regulation Role Signal Pathway Signal Transduction Site Structure Testing base clinical development conditional knockout conditional mutant gland development human disease insight migration mutant organ growth programs recruit regenerative treatment src Homology Region 2 Domain transcriptome transcriptome sequencing

项目摘要

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.

项目摘要该项目的长期目标是研究泪腺中FGF信号的调节发展，这对理解患病的富富腺的病因具有重要意义人类。泪腺通过主要由FGF驱动的分支形态发生过程发展。我们以前已经表明，RAS-MAPK途径是FGF信号传导的重要下游目标泪腺形态发生。在此应用中，我们将测试PLCγ也是关键的假设 FGF信号传导的调节因子在泪腺发育中。使用条件突变小鼠和细胞培养模型，我们将研究FGF受体募集和激活PLCγ的方式。我们还将检查串扰在泪腺发育中PLCγ和RAS信号传导之间。最后，我们将测试PLCγ的假设通过控制FGF受体的内吞作用来调节FGF信号的强度。通过调查调节鼠泪腺中FGF信号传导，该项目将有助于医学研究人类泪腺缺乏症和干眼病。