title: Melatonin inhibits embryonic salivary gland branching morphogenesis by regulating both epithelial cell adhesion and morphology.
abstract: Many organs, including salivary glands, lung, and kidney, are formed by epithelial branching during embryonic development. Branching morphogenesis occurs via either local outgrowths or the formation of clefts that subdivide epithelia into buds. This process is promoted by various factors, but the mechanism of branching morphogenesis is not fully understood. Here we have defined melatonin as a potential negative regulator or "brake" of branching morphogenesis, shown that the levels of it and its receptors decline when branching morphogenesis begins, and identified the process that it regulates. Melatonin has various physiological functions, including circadian rhythm regulation, free-radical scavenging, and gonadal development. Furthermore, melatonin is present in saliva and may have an important physiological role in the oral cavity. In this study, we found that the melatonin receptor is highly expressed on the acinar epithelium of the embryonic submandibular gland. We also found that exogenous melatonin reduces salivary gland size and inhibits branching morphogenesis. We suggest that this inhibition does not depend on changes in either proliferation or apoptosis, but rather relates to changes in epithelial cell adhesion and morphology. In summary, we have demonstrated a novel function of melatonin in organ formation during embryonic development.
authors: Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors: Aya
authors: A
authors: Obana-Koshino
authors: Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors: Hitomi
authors: H
authors: Ono
authors: Division for Interdisciplinary Dentistry, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors: Jiro
authors: J
authors: Miura
authors: Clinical Laboratory, Osaka University Dental Hospital, Suita, Osaka, Japan.
authors: Manabu
authors: M
authors: Sakai
authors: Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan; Laboratory of Oral Chronobiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors: Hitoshi
authors: H
authors: Uchida
authors: Laboratory of Oral Chronobiology, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors: Wataru
authors: W
authors: Nakamura
authors: Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors: Kanji
authors: K
authors: Nohara
authors: Department of Biology, Tokyo Medical and Dental University, Ichikawa, Chiba, Japan.
authors: Yusuke
authors: Y
authors: Maruyama
authors: Department of Biology, Tokyo Medical and Dental University, Ichikawa, Chiba, Japan.
authors: Atsuhiko
authors: A
authors: Hattori
authors: Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
authors: Takayoshi
authors: T
authors: Sakai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D048430:Cell Shape / Q000235:genetics; D047108:Embryonic Development; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008550:Melatonin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D011247:Pregnancy; D044122:Receptor, Melatonin, MT1 / Q000096:biosynthesis* / Q000235:genetics; D044123:Receptor, Melatonin, MT2 / Q000096:biosynthesis* / Q000235:genetics; D012469:Salivary Glands / Q000196:embryology / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D008550:Melatonin