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Runx1 is involved in the fusion of the primary and the secondary palatal shelves |
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| Authors: | Kesinee Charoenchaikorn David P. Rice Tadashi Honjo Yuko Shintaku Asami Wakamatsu Yoshiaki Ito Irma Thesleff Takashi Yamashiro |
| Affiliation: | a Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka University, Suita, Japan b Department of Anatomy and Embryology, Biomolecular and Integrated Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan c Department of Orthodontics, Institute of Dentistry and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland d Department of Craniofacial Development, King's College, London, UK e Department of Orthodontics, King's College, London, UK f Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan g Institute of Molecular and Cell Biology and Oncology Research Institute, Singapore, Singapore h Division of Orthodontics and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Sendai, Japan i Developmental Biology Programme, Institute of Biotechnology, University of Helsinki, Helsinki, Finland j Center for Tsukuba Advanced Research Alliance and JST-ERATO Environmental Response Project, University of Tsukuba, Tsukuba, Japan k Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan |
| Abstract: | Runx1 is expressed in medial edge epithelial (MEE) cells of the palatal shelf. Conditionally rescued Runx1−/− mice showed limited clefting in the anterior junction between the primary and the secondary palatal shelves, but not in the junction between the secondary palates. In wild type mice, the fusing epithelial surface exhibited a rounded cobblestone-like appearance, while such cellular prominence was less evident in the Runx1 mutants. We also found that Fgf18 was expressed in the mesenchyme underlying the MEE and that locally applied FGF18 induced ectopic Runx1 expression in the epithelium of the palatal explants, indicating that Runx1 was induced by mesenchymal Fgf18 signaling. On the other hand, unpaired palatal explant cultures revealed the presence of anterior-posterior (A-P) differences in the MEE fates and fusion mechanism. Interestingly, the location of anterior clefting in Runx1 mutants corresponded to the region with different MEE behavior. These data showed a novel function of Runx1 in morphological changes in the MEE cells in palatal fusion, which is, at least in part, regulated by the mesenchymal Fgf signaling via an epithelial-mesenchymal interaction. |
| Keywords: | Fgf, fibroblast growth factor Fgfr, fibroblast growth factor receptor SEM, Scanning Electron Microscopy TEM, transmission electron microscopy Tgf, transforming growth factor MEE, Medial edge epithelium |
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