Regulation of FGF signaling in lacrimal gland development

FGF信号在泪腺发育中的调节

• 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
• 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

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.

项目概要 该项目的长期目标是研究泪腺中 FGF 信号传导的调控 发育，这对于了解泪腺患病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育。 我们之前已经证明 Ras-MAPK 通路是 FGF 信号传导的重要下游靶点 泪腺形态发生。在此应用中，我们将测试 PLCγ 也是关键的假设 泪腺发育中 FGF 信号传导的调节因子。使用条件突变小鼠和细胞培养 模型中，我们将研究 FGF 受体如何招募和激活 PLCγ。我们还将检查串扰 PLCγ 和 Ras 信号在泪腺发育中的关系。最后，我们将检验 PLCγ 的假设 通过控制 FGF 受体的内吞作用来调节 FGF 信号传导的强度。通过调查 小鼠泪腺中 FGF 信号的调节，该项目将有助于治疗治疗的医学研究 人类泪腺缺乏症和干眼症。