Ras signaling and RREB1 are required for the dissociation of medial edge epithelial cells in murine palatogenesis

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  • Toshihiro Inubushi
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, Osaka 5650871, Japan
  • Ayaka Fujiwara
    First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan
  • Takumi Hirose
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, Osaka 5650871, Japan
  • Gozo Aoyama
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, Osaka 5650871, Japan
  • Toshihiro Uchihashi
    First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan
  • Naoki Yoshida
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, Osaka 5650871, Japan
  • Yuki Shiraishi
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, Osaka 5650871, Japan
  • Yu Usami
    Department of Oral Pathology, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan
  • Hiroshi Kurosaka
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, Osaka 5650871, Japan
  • Satoru Toyosawa
    Department of Oral Pathology, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan
  • Susumu Tanaka
    First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan
  • Tetsuro Watabe
    Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 1138549, Japan
  • Mikihiko Kogo
    First Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Osaka University, Osaka 5650871, Japan
  • Takashi Yamashiro
    Department of Orthodontics and Dentofacial Orthopedics, Osaka University Graduate School of Dentistry, Osaka 5650871, Japan

抄録

<jats:title>ABSTRACT</jats:title> <jats:p>Cleft palate is one of the major congenital craniofacial birth defects. The etiology underlying the pathogenesis of cleft palate has yet to be fully elucidated. Dissociation of the medial edge epithelium (MEE) at the contacting region of palatal shelves and subsequent migration or apoptosis of MEE cells is required for proper MEE removal. Ras-responsive element-binding protein 1 (RREB1), a RAS transcriptional effector, has recently been shown to play a crucial role in developmental epithelial–mesenchymal transition (EMT), in which loss of epithelial characteristics is an initial step, during mid-gastrulation of embryonic development. Interestingly, the involvement of RREB1 in cleft palate has been indicated in humans. Here, we demonstrated that pan-Ras inhibitor prevents the dissociation of MEE during murine palatal fusion. Rreb1 is expressed in the palatal epithelium during palatal fusion, and knockdown of Rreb1 in palatal organ culture resulted in palatal fusion defects by inhibiting the dissociation of MEE cells. Our present findings provide evidence that RREB1-mediated Ras signaling is required during palatal fusion. Aberrant RREB1-mediated Ras signaling might be involved in the pathogenesis of cleft palate.</jats:p>

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