Format

Send to

Choose Destination
Development. 2018 Jul 9. pii: dev.164822. doi: 10.1242/dev.164822. [Epub ahead of print]

RDH10-mediated retinol metabolism and RARα-mediated retinoic acid signaling are required for submandibular salivary gland initiation.

Author information

1
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, USA.
2
Division of Plastic Surgery, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati OH 45229, USA.
3
Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
4
Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222, USA.
5
Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, USA lisa.sandell@louisville.edu.

Abstract

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.

KEYWORDS:

Embryo; RAR; RDH10; Retinoic acid; Salivary gland; Submandibular

PMID:
29986869
DOI:
10.1242/dev.164822

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center