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：
8593298
负责人：
Xin Zhang
金额：
$ 38.41万
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：
2009-01-01 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8593298
关键词：
Ablation Affect Alleles Binding Cell Proliferation Clinical Communication Conjunctival Epithelium Defect Development Diagnosis Disease Dry Eye Syndromes Epithelial Epithelium Etiology Extracellular Matrix Eye Abnormalities Family Fibroblast Growth Factor Fibroblast Growth Factor Receptors Future Genes Genetic Genetic Models Goals Human Human Development Intervention Lacrimal gland structure Lead MAP Kinase Gene Mediating Mediator of activation protein Medical Research Mesenchymal Mesenchyme Molecular Morphogenesis Mus Mutant Strains Mice Neural Crest Pathway interactions Process Regulation Role Signal Pathway Signal Transduction Site Study models Testing Work activating transcription factor base cell motility gland development human disease insight lacrimal migration mutant public health relevance research study transcription factor

项目摘要

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 diseased lacrimal gland in human. The lacrimal gland develops through a branching morphogenesis process primarily driven by FGF signaling. This application will focus on the regulatory mechanism of FGF expression in the periocular mesenchyme and the downstream mediators of Ras signaling in the lacrimal gland epithelium. We will examine the signaling crosstalk between Ras and PI3K pathways. We will also investigate the role of ETS family transcription factors activated by Ras-MAPK signaling in lacrimal gland development. Finally, we will develop mouse genetic models to test the hypothesis that neural crest development is critical for Fgf10 expression in lacrimal gland. 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.

描述（由申请人提供）：该项目的长期目标是研究FGF信号在泪腺发育中的调节，这对于了解人类患病泪腺的病因学具有重要意义。泪腺通过主要由 FGF 信号驱动的分支形态发生过程发育。本申请将重点研究眼周间质中 FGF 表达的调节机制以及泪腺上皮中 Ras 信号传导的下游介质。我们将检查 Ras 和 PI3K 通路之间的信号串扰。我们还将研究 Ras-MAPK 信号激活的 ETS 家族转录因子在泪腺发育中的作用。最后，我们将开发小鼠遗传模型来检验神经嵴发育对于泪腺中 Fgf10 表达至关重要的假设。通过研究小鼠泪腺中 FGF 信号传导的调节，该项目将有助于治疗人类先天性眼病的医学研究，并增进我们对间充质-上皮相互作用范例的理解。