Cdc42 is crucial for facial and palatal formation during craniofacial development
Mutsuko Oshima-Nakayama,
Atsushi Yamada,
Tamaki Kurosawa,
Ryo Aizawa,
Dai Suzuki,
Yoshiro Saito,
Hidetoshi Kassai,
Yuki Sato,
Matsuo Yamamoto,
Tatsuo Shirota,
Atsu Aiba,
Koutaro Maki,
Ryutaro Kamijo
Affiliations
Mutsuko Oshima-Nakayama
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.; Department of Orthodontics, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan
Atsushi Yamada
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.; Corresponding author at: Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
Tamaki Kurosawa
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
Ryo Aizawa
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.; Department of Periodontology, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan
Dai Suzuki
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
Yoshiro Saito
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.; Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan
Hidetoshi Kassai
Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
Yuki Sato
Department of Orthodontics, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan
Matsuo Yamamoto
Department of Periodontology, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan
Tatsuo Shirota
Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan
Atsu Aiba
Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
Koutaro Maki
Department of Orthodontics, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan
Ryutaro Kamijo
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
Craniofacial deformities with multifactorial etiologies, such as cleft palate and facial dysmorphism, represent some of the most frequent congenital birth defects seen in humans. Their pathogeneses are often related to cranial neural crest (CNC) cells. During CNC cell migration, changes in cell shape and formation, as well as maintenance of subcellular structures, such as filopodia and lamellipodia, are dependent on the complex functions of Rho family small GTPases, which are regulators of actin cytoskeletal organization. Cdc42, a member of the Rho family of small GTPases, is known to play critical roles in organogenesis of various tissues. To investigate the physiological functions of Cdc42 during craniofacial development, we generated CNC-derived cell-specific inactivated Cdc42 mutant mice (Cdc42fl/fl;P0-cre). Most of the Cdc42fl/fl;P0-cre neonates were viable at birth, though they appeared weaker and no milk was found in their stomachs, and all died within a few days. They had a short face and intracranial bleeding, and abnormal calcification of the cranium. Cdc42fl/fl;P0-cre neonates also demonstrated a cleft palate and there was no fusion of the secondary palate because of failure of palatal shelf elongation for the process of palate closure. Cdc42 is crucial for facial and palatal formation during craniofacial development. Keywords: Cdc42, Cleft palate, Conditional knockout mice, P0-cre transgenic mice
