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.
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.
|Balasubramanian, Revathi; Zhang, Xin (2016) Mechanisms of FGF gradient formation during embryogenesis. Semin Cell Dev Biol 53:94-100|
|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|
|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|
|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|
|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|
|Cai, Zhigang; Tao, Chenqi; Li, Hongge et al. (2013) Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma. Development 140:2711-23|
|Carbe, Christian; Garg, Ankur; Cai, Zhigang et al. (2013) An allelic series at the paired box gene 6 (Pax6) locus reveals the functional specificity of Pax genes. J Biol Chem 288:12130-41|
|Qu, Xiuxia; Pan, Yi; Carbe, Christian et al. (2012) Glycosaminoglycan-dependent restriction of FGF diffusion is necessary for lacrimal gland development. Development 139:2730-9|
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