TGF-Beta Type II and III Receptors Signaling for Fate of MEE in Palatogenesis

  • Dr Akira Nakajima, Nihon University School of Dentistry, Japan
  • Dr Yoshihiro Ito, University of Illinois, School of Dentistry, United States
  • Dr Narihiro Mitsui, Nihon University School of Dentistry, Japan
  • Prof Masao Maeno, Nihon University School of Dentistry, Japan
  • Prof Koichi Iwata, Japan
  • Prof Charles Shuler, University of British Colombia, Canada
  • Prof Noriyoshi Shimizu, Nihon University School of Dentistry, Japan

The molecular mechanisms regulating palatogenesis remain incompletely characterized but are most likely to be involved in the molecular etiology for cleft palate. We previously identified knocked down of TGF-beta type III receptor (TβR-III) using small interfering RNA (siRNA) in palatogenesis, and it induced delayed palatal fusion. The generated TGF-beta type II receptor (TβR-II) conditional knock out mice also induced partial cleft palate.
Objective: The objective was to investigate the fate of the medial edge epithelium (MEE) when both TβR-II and III receptors (TβR-II/III) were knocked down during palatogenesis.
Methods: E13 palatal shelves were dissected and organ cultured in BGjb medium with siRNA (300 nM). Real-time PCR was performed to analyze TβR-II/III gene expressions after siRNA knock down treatment. We also observed phenotype of palate at E13+72h using H-E staining.
Results: siRNA treatment of TβR-II/III decreased both gene expressions compared with control. Approximately 60% palates indicated completely no fused and 30% palates were partially fused at E13+72h when TβR-II/III knocked down, although all control palate were completely fused.
Conclusion: We suggested that TβR-II and III were strongly linked to events during palatogenesis. In addition, we provided evidence that TβR-II and TβR-III siRNA treatments resulted in persistent MEE cell proliferation, which has been shown to be linked to a failure to complete palatal fusion events. (Supported by NIDCR grants PO1DE-12941, RO1DE-16296, MEXT Grant-in-Aid for Scientific Research (C) grants 20592415, and Nihon University Research Grant).