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 PLC? 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 PLC?. We will also examine the crosstalk between PLC? and Ras signaling in lacrimal gland development. Finally, we will test the hypothesis that PLC? 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.

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 the dry eye disease.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Mckie, George Ann
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Garg, Ankur; Zhang, Xin (2017) Lacrimal gland development: From signaling interactions to regenerative medicine. Dev Dyn 246:970-980
Cvekl, Ales; Zhang, Xin (2017) Signaling and Gene Regulatory Networks in Mammalian Lens Development. Trends Genet 33:677-702
Mathew, Grinu; Hannan, Abdul; Hertzler-Schaefer, Kristina et al. (2016) Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor. Proc Natl Acad Sci U S A 113:13156-13161
Tao, Chenqi; Zhang, Xin (2016) Retinal Proteoglycans Act as Cellular Receptors for Basement Membrane Assembly to Control Astrocyte Migration and Angiogenesis. Cell Rep 17:1832-1844
Balasubramanian, Revathi; Zhang, Xin (2016) Mechanisms of FGF gradient formation during embryogenesis. Semin Cell Dev Biol 53:94-100
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
Tao, Chenqi; Zhang, Xin (2014) Development of astrocytes in the vertebrate eye. Dev Dyn 243:1501-10
Pan, Yi; Carbe, Christian; Kupich, Sabine et al. (2014) Heparan sulfate expression in the neural crest is essential for mouse cardiogenesis. Matrix Biol 35:253-65
Cai, Zhigang; Tao, Chenqi; Li, Hongge et al. (2013) Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma. Development 140:2711-23

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