Date on Master's Thesis/Doctoral Dissertation

12-2016

Document Type

Master's Thesis

Degree Name

M.S.

Department

Oral Biology

Degree Program

Oral Biology, MS

Committee Chair

Sandell, Lisa

Committee Co-Chair (if applicable)

Liang, Shuang

Committee Member

Liang, Shuang

Committee Member

Darling, Douglas

Author's Keywords

salivary; retinoic; keratin; submandibular; vitamin A; epithelium

Abstract

Vitamin A metabolism, which produces the signaling molecule Retinoic Acid (RA), has been demonstrated to be important for growth and branching morphogenesis of mammalian embryonic salivary gland epithelium. However, it is not known whether RA functions directly within epithelial cells or in associated tissues that influence morphogenesis of salivary epithelium. Moreover, downstream targets of RA transcriptional regulation have not been identified. Here we show that canonical RA signaling occurs in multiple tissues of embryonic mouse salivary glands, including epithelium, associated parasympathetic ganglion neurons, and non‑neuronal mesenchyme. By culturing epithelium explants in isolation from other tissues we demonstrate that RA influences epithelial morphogenesis by direct action in that tissue. Moreover, we demonstrate that inhibition of RA signaling represses FGF10 signaling and upregulates expression of the basal epithelial keratins Krt5 and Krt14. Importantly, we show that the stem cell gene Kit is regulated inversely from Krt5/Krt14 by RA signaling. Thus, expression of Krt5 and Krt14 are independent of stem cell character in this context. These data suggest that RA or chemical inhibitors of RA signaling could potentially be used for modulating growth and differentiation of epithelial stem cells for the purpose of re‑populating damaged glands or generating bioengineered organs.

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