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Galina Dvoriantchikova, Steve Pappas, Gabriel Gaidosh, Wensi Tao, David T Tse, Dmitry V Ivanov, Daniel Pelaez; Molecular profiling of the developing lacrimal gland. Invest. Ophthalmol. Vis. Sci. 2016;57(12):231.
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© ARVO (1962-2015); The Authors (2016-present)
The lacrimal gland (LG) produces tears to help maintain the physiological function of the ocular surface. Dysfunction of the LG leads to dry eye disease, which if left untreated results in visual impairment. Although normal function of the LG is essential for vision and thus human well-being, the LG remains rather poorly understood. In particular, little is known about the mechanisms of LG development. The purpose of this study was to identify genes and signaling cascades involved in LG development.
To identify these genes, we compared gene expression profiles of developing (embryonic day 16.5; E16.5) and adult (3 month) LGs using Mouse Exonic Evidence Based Oligonucleotide (MEEBO) microarrays. For statistical analysis, microarray data were examined for differences by One-way ANOVA or Student's t-test. Values of P < 0.05 were designated as statistically significant. Differential data were validated by quantitative RT-PCR, and several corresponding proteins were confirmed by western blot analysis and immunohistochemistry.
Our microarray data revealed a significant difference in gene expression between developing and adult LGs. We found that 1469 genes were significantly up-regulated (greater than 2-fold change and P<0.05) in E16.5 LGs compared to adult LGs. Meanwhile, 2553 genes were significantly up-regulated in adult LGs. Whereas developmental processes were significantly up-regulated in E16.5 LGs, metabolic processes were predominantly up-regulated in adult LGs. An in silico reconstruction of cellular networks revealed increased activity of NOTCH (Notch1, Notch3, Jag1, Jag2, and Dlk1), WNT (Fzd2, Fzd9, Wnt2b, Wnt11, Wnt5a, Tcf4, Ror2, etc.), and TGFβ (Tgfb1, Tgfb3, Tgfbr2, Tgfbr3, Smad2, and Smad3) signaling cascades in the developing LG compared to the adult LG. These signaling cascades are involved in the regulation of epithelial-to-mesenchymal and mesenchymal-to-epithelial transition. Importantly, some detected genes (including Dlk1, Ptn, and Ror2) were previously shown to play roles in branching morphogenesis within the salivary and mammary glands.
Our findings suggest that NOTCH-, WNT-, and TGFβ-regulated epithelial-to-mesenchymal and mesenchymal-to-epithelial transition may be critical mechanisms in LG development. Our data also indicate that the mechanisms of LG development share some similarities with those of salivary and mammary gland development.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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