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Retinoic acid signaling regulates Krt5 and Krt14 independently of stem cell markers in submandibular salivary gland epithelium
Author(s) -
Abashev Timur M.,
Metzler Melissa A.,
Wright Diana M.,
Sandell Lisa L.
Publication year - 2017
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24476
Subject(s) - biology , retinoic acid , epithelium , microbiology and biotechnology , morphogenesis , stem cell , keratin 5 , keratin 14 , progenitor cell , embryonic stem cell , keratin , medicine , cell culture , genetically modified mouse , transgene , gene , genetics
Background : Retinoic acid (RA), the active metabolite of vitamin A, 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 regulation have not been identified. Results : Here, we show that canonical RA signaling occurs in multiple tissues of embryonic mouse salivary glands, including epithelium, associated parasympathetic ganglion neurons, and nonneuronal mesenchyme. By culturing epithelium explants in isolation from other tissues, we demonstrate that RA influences epithelium morphogenesis by direct action in that tissue. Moreover, we demonstrate that inhibition of RA signaling represses cell proliferation and expression of FGF10 signaling targets, and upregulates expression of basal epithelial keratins Krt5 and Krt14 . Importantly, we show that the stem cell gene Kit is regulated inversely from Krt5 / Krt14 by RA signaling. Conclusions : RA regulates Krt5 and Krt14 expression independently of stem cell character in developing salivary epithelium. 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. Developmental Dynamics 246:135–147, 2017 . © 2016 Wiley Periodicals, Inc.