Retinoic acid regulates embryonic development of mammalian submandibular salivary glands.
Organogenesis is orchestrated by cell and tissue interactions mediated by molecular signals. Identification of relevant signals, and the tissues that generate and receive them, are important goals of developmental research. Here, we demonstrate that Retinoic Acid (RA) is a critical signaling molecule important for morphogenesis of mammalian submandibular salivary glands (SMG). By examining late stage RA deficient embryos of Rdh10 mutant mice we show that SMG development requires RA in a dose-dependent manner. Additionally, we find that active RA signaling occurs in SMG tissues, arising earlier than any other known marker of SMG development and persisting throughout gland morphogenesis. At the initial bud stage of development, we find RA production occurs in SMG mesenchyme, while RA signaling occurs in epithelium. We also demonstrate active RA signaling occurs in glands cultured ex vivo, and treatment with an inhibitor of RA signaling blocks growth and branching. Together these data identify RA signaling as a direct regulator of SMG organogenesis.
University of Louisville School of Dentistry, Department of Molecular, Cellular and Craniofacial Biology, Louisville, KY 40201, USA.
Diana M
DM
Wright
University of Louisville School of Dentistry, Department of Molecular, Cellular and Craniofacial Biology, Louisville, KY 40201, USA.
Deanna E
DE
Buenger
University of Louisville School of Dentistry, Department of Molecular, Cellular and Craniofacial Biology, Louisville, KY 40201, USA.
Timur M
TM
Abashev
University of Louisville School of Dentistry, Department of Molecular, Cellular and Craniofacial Biology, Louisville, KY 40201, USA.
Robert P
RP
Lindeman
University of Louisville School of Dentistry, Department of Molecular, Cellular and Craniofacial Biology, Louisville, KY 40201, USA.
Jixiang
J
Ding
University of Louisville School of Dentistry, Department of Molecular, Cellular and Craniofacial Biology, Louisville, KY 40201, USA. Electronic address: Lisa.Sandell@Louisville.edu.
Lisa L
LL
Sandell
D000429:Alcohol Oxidoreductases / Q000502:physiology; D000818:Animals; D047108:Embryonic Development / Q000187:drug effects*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D015398:Signal Transduction; D013363:Submandibular Gland / Q000196:embryology*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D014801:Vitamin A / Q000378:metabolism
D014801:Vitamin A; D014212:Tretinoin; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase
Branching; Organogenesis; Rdh10; Retinoic Acid; Retinol dehydrogenase; Salivary; Submandibular; Vitamin A