Retinoic Acid Induces Myogenic Tongue Abnormalities in Fetal Mice

RETINOIC ACID INDUCES MYOGENIC TONGUE ABNORMALITIES IN FETAL MICE Wei Cong, Bo Liu, Ru Wang, Jing Xiao, Department of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian, China; Department of Stomatology, the First Affiliated Hospital, Dalian Medical University, Dalian, China Objective: To study the aberrant morphogenesis and underlying mechanism of RA induced tongue malformation in fetal mice. Study Design: Exogenous RA was used to induce tongue malformation. The histological changes of tongue were characterized by HE staining and transmission electron microscopy. Myogenic differentiation was measured by Immunohistochemical assays and qRT-PCR of Myf5 and MyoD. The signaling genes were evaluated by qRT-PCR. Results: In +RA fetal mice, the tongues failed to descend and flatten while maintaining a higher position at E14.5. Subcellular changes of genioglossus showed the myofibrils failed to form normal structures of sarcomeres, and muscle fibers were disorderly arranged. The levels of Myf5 and MyoD were reduced. The downregulation of Wnt5a was positively correlated with Camk2d and inversely correlated with Tbx1, Ror2, and PKCd. Conclusions: The Wnt5a/CaMKII pathway may be involved in hypoplasia and disorder of tongue with decreased myogenic differentiation induced by RA.