title: Implications of the Wnt5a/CaMKII pathway in retinoic acid-induced myogenic tongue abnormalities of developing mice.
abstract: Although proper tongue development is relevant to other structures in the craniofacial region, the molecular details of muscle development in tongue remain poorly understood. Here, we report that pregnant mice treated with retinoic acid (+RA) produce embryos with tongue malformation and a cleft palate. Histological analyses revealed that at E14.5, the tongues of +RA fetuses failed to descend and flatten. Ultrastructural analysis showed that at perinatal stage E18.5, the myofilaments failed to form normal structures of sarcomeres, and arranged disorderly in the genioglossus. The proliferation and levels of myogenic determination markers (Myf5 and MyoD) and myosin in the genioglossus were profoundly reduced. Wnt5a and Camk2d expressions were down-regulated, while levels of Tbx1, Ror2, and PKCδ were up-regulated in the tongues of +RA fetuses. In mock- and Wnt5a-transfected C2C12 (Wnt5a-C2C12) cells, Wnt5a overexpression impaired proliferation, and maintained Myf5 at a relative high level after RA treatment. Furthermore, Wnt5a overexpression positively correlated with levels of Camk2d and Ror2 in C2C12 cells after RA exposure. These data support the hypothesis that the Wnt5a/CaMKII pathway is directly involved in RA-induced hypoplasia and disorder of tongue muscles.
authors.affiliation: Department of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cong
authors.affiliation: Department of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Shuqing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Mingzhong
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Stomatology, the First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, 116011, China.
authors.forename: Ru
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D002972:Cleft Palate / Q000139:chemically induced; D004622:Embryo, Mammalian / Q000196:embryology; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D024510:Muscle Development / Q000187:drug effects*; D017570:MyoD Protein / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D011247:Pregnancy; D051745:Protein Kinase C-delta / Q000096:biosynthesis; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000096:biosynthesis; D012518:Sarcomeres / Q000473:pathology; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D014059:Tongue / Q000002:abnormalities* / Q000196:embryology; D014212:Tretinoin / Q000009:adverse effects* / Q000494:pharmacology; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: C497418:Myf5 protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D014212:Tretinoin; C497259:Prkcd protein, mouse; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse; D051745:Protein Kinase C-delta; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D009218:Myosins