Regulation of FGF signaling in lacrimal gland development

描述(申请人提供)：该项目的长期目标是研究成纤维细胞生长因子信号在泪腺发育中的调控，这对了解人类泪腺疾病的病因具有重要意义。泪腺的发育主要是由成纤维细胞生长因子信号驱动的分枝形态发生过程。这一应用将集中在眼周间充质中成纤维细胞生长因子表达的调节机制和泪腺上皮中RAS信号的下游介体。我们将研究RAS和PI3K通路之间的信号串扰。我们还将研究由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验证神经脊发育对泪腺Fgf10表达至关重要的假设。通过研究成纤维细胞生长因子信号在小鼠泪腺中的调控，本项目将有助于治疗人类先天性眼病的医学研究，并促进我们对间充质-上皮相互作用范式的理解。

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.