Open AccessRDH10-mediated retinol metabolism and RARα-mediated retinoic acid signaling are required for submandibular salivary gland initiation
Author(s) -
Melissa A. Metzler,
Swetha Raja,
Kelsey H. Elliott,
Regina M. Friedl,
Nhut Quang Huy Tran,
Samantha A. Brugmann,
Melinda Larsen,
Lisa L. Sandell
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.164822
Subject(s) - retinoic acid , biology , mesenchyme , salivary gland , submandibular gland , retinoid , microbiology and biotechnology , endocrinology , sublingual gland , medicine , saliva , biochemistry , embryo , gene
In mammals, the epithelial tissues of major salivary glands generate saliva and drain it into the oral cavity. For submandibular salivary glands (SMG), it is known that the epithelial tissues arise during embryogenesis from naïve oral ectoderm adjacent to the base of the tongue, which begins to thicken, express SOX9, and invaginate into underlying mesenchyme. The developmental mechanisms initiating salivary gland development remain unexplored. In this study we show that retinoic acid (RA) signaling activity at the site of gland initiation is co-localized with expression of retinol metabolic genes Rdh10, and Aldh1a2 in the underlying SMG mesenchyme. Utilizing a novel ex vivo assay for SMG initiation developed for this study, we show that RDH10 and RA are required for salivary gland initiation. Moreover, we show that the requirement for RA in gland initiation involves canonical signaling through retinoic acid receptors (RAR). Finally, we show that RA signaling essential for gland initiation is transduced specifically through RARα, with no contribution from other RAR isoforms. This is the first study to identify a molecular signal regulating mammalian salivary gland initiation.