The ocular lens is composed of two cell types; epithelial cells and fiber cells. Lens epithelial cells are the undifferentiated precursor to lens fiber cells which arise from epithelial cells. As these cuboidal cells go through differentiation into fiber cells, they go through major gene expression changes that elongate the cells and promote transparency. Cell differentiation is controlled by FGF receptor (FGFR) signaling and PTEN. FGFR signaling promotes cell differentiation while PTEN antagonizes it. In this project, I attempted to determine the molecular mechanism tying FGFR activation to fiber cell differentiation. Using a bioinformatic analysis of gene expression induced by vitreous humor exposure in wild type lens epithelial cells and in lens epithelial cells lacking FGFR signaling or PTEN or both FGFR signaling and PTEN has allowed for the identification of genes involved in the signaling pathway. In the comparison of the wildtype lens to the FGFR triple knockout (TKO) lens, I found that many of the most highly downregulated genes corresponded to crystallins. Crystallins are highly expressed in fiber cells because they promote transparency, but they are downregulated in TKO lenses because they do not differentiate. In the future, lenses with different combinations of functional FGFR signaling and PTEN will be exposed to vitreous humor for longer periods of time allowing for further changes in gene expression that will expand upon our elucidation of the mechanism of FGFR signaling and PTEN. Understanding the FGFR signaling pathway will be useful for learning about eye development in mice, the origin of diseases of the eye like cataracts and anterior segment dysgenesis, and the development of diseases, like cancer, where FGFR signaling and PTEN clearly play a role. This project has been valuable in giving me experience in bioinformatics which I will use in my future career as a bioinformatician.
Author: Anthony Petulla, Biology Major
Advisor: Michael Robinson, Biology
Graduate Advisor: Anil Upreti, Biology
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