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.

Public Health Relevance

This project investigates the mechanism of FGF signaling in lacrimal gland development. It is expected to contribute to our understanding of this important pathway in human development and disease, and inform future development of clinical interventions to treat dry eye syndrome.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (BVS)
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Mckie, George Ann
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Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
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Tao, Chenqi; Zhang, Xin (2014) Development of astrocytes in the vertebrate eye. Dev Dyn 243:1501-10
Cai, Zhigang; Grobe, Kay; Zhang, Xin (2014) Role of heparan sulfate proteoglycans in optic disc and stalk morphogenesis. Dev Dyn 243:1310-6
Hertzler-Schaefer, Kristina; Mathew, Grinu; Somani, Ally-Khan et al. (2014) Pten loss induces autocrine FGF signaling to promote skin tumorigenesis. Cell Rep 6:818-26
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Carbe, Christian; Hertzler-Schaefer, Kristina; Zhang, Xin (2012) The functional role of the Meis/Prep-binding elements in Pax6 locus during pancreas and eye development. Dev Biol 363:320-9
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Cai, Zhigang; Feng, Gen-Sheng; Zhang, Xin (2010) Temporal requirement of the protein tyrosine phosphatase Shp2 in establishing the neuronal fate in early retinal development. J Neurosci 30:4110-9