title: Retinoic acid alters the proliferation and survival of the epithelium and mesenchyme and suppresses Wnt/β-catenin signaling in developing cleft palate.
abstract: Retinoic acid (RA) contributes to cleft palate; however, the cellular and molecular mechanisms responsible for the deleterious effects on the developing palate are unclear. Wnt signaling is a candidate pathway in the cleft palate and is associated with RA in organ development; thus, we aim to investigate whether RA-induced cleft palate also results from altered Wnt signaling. Administration of RA to mice altered cell proliferation and apoptosis in craniofacial tissues by regulating molecules controlling cell cycle and p38 MAPK signaling, respectively. This altered cell fate by RA is a crucial mechanism contributing to 100% incidence of cleft palate. Moreover, Wnt/β-catenin signaling was completely inhibited by RA in the early developing palate via its binding and activation with RA receptor (RAR) and is responsible for RA-induced cleft palate. Furthermore, PI3K/Akt signaling was also involved in actions of RA. Our findings help in elucidating the mechanisms of RA-induced cleft palate.
authors.affiliation: 1] Department of Plastic and Burn Surgery, Guangzhou Red Cross Hospital, Guangzhou 510220, People's Republic of China [2] Department of Plastic and Cosmetic Surgery, Nan Fang Hospital, Guangzhou 510515, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: Y
authors.initials: Y
authors.lastname: Liao
authors.forename: S
authors.initials: S
authors.lastname: Tang
authors.forename: F
authors.initials: F
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002972:Cleft Palate / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D005260:Female; D020287:In Situ Nick-End Labeling; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011247:Pregnancy; D014212:Tretinoin / Q000494:pharmacology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D014212:Tretinoin