title: Inhibition of Wnt/β-catenin pathway by Dickkopf-1 [corrected] affects midfacial morphogenesis in chick embryo.
abstract: The development of the vertebrate face is regulated by complex interactions among several signaling pathways. Dickkopf-1 (Dkk-1), an inhibitor of the Wnt/β-catenin signaling pathway, can affect midfacial morphogenesis. The downstream target genes of the Wnt/β-catenin signaling pathway in morphogenesis of the developing upper jaw and lip remain unknown. To investigate the functional roles of Wnt/β-catenin signaling in facial development, we performed a loss-of-function experiment using local implantation of beads soaked with Dkk-1 during lip fusion at the maxillary prominence of chick embryos at stage 22(HH22). Antagonism of Wnt/β-catenin signaling by Dkk-1 induced deformities of the premaxilla and jugal bone, which are derived from the maxillary mesenchyme. Real-time and semi-quantitative RT-PCR analysis showed the significant reduction of Lhx8, Msx1 and Msx2 expression levels around the beads in the maxillary mesenchyme at 6 and 24 h after bead implantation. Time course experiments in the HH 22 embryos showed the effect of Dkk-1 on Lhx8, Msx1 and Msx2 expression was not significant after 48 h of the treatment. At HH 26 when the fusion of facial primordial started, Dkk-1 application did not exhibit any significant reduction of those genes. Our findings suggested that Dkk-1 regulates maxillary morphogenesis in chick embryos through Lhx8, Msx1 and Msx2 signals. Wnt/β-catenin signaling is responsible for intrinsic upper jaw development before the lip fusion.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: mkawaka@naramed-u.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kawakami
authors.affiliation: Department of Anatomy and Neurosciences, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: okuda@naramed-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuda
authors.affiliation: Department of Anatomy and Neurosciences, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: radha815@naramed-u.ac.jp.
authors.forename: Kouko
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: tkirita@naramed-u.ac.jp.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.affiliation: Department of Anatomy and Neurosciences, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: akiow@naramed-u.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Wanaka
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000502:physiology*; D002642:Chick Embryo; D005123:Eye / Q000196:embryology; D005145:Face / Q000196:embryology; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D008437:Maxilla / Q000196:embryology / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D009024:Morphogenesis; D060449:Wnt Signaling Pathway
chemical_list: D030161:Avian Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D060850:LIM-Homeodomain Proteins; D051957:MSX1 Transcription Factor; C084119:MSX2 protein
keywords: Chick embryo; Craniofacial development; Dickkopf-1 (Dkk-1); Lhx8; Wnt/β-catenin signaling