Cdc42 is crucial for facial and palatal formation during craniofacial development.
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 theCdc42fl/fl;P0-creneonates 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-creneonates 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.
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.
Mutsuko
M
Oshima-Nakayama
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
Atsushi
A
Yamada
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
Tamaki
T
Kurosawa
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.
Ryo
R
Aizawa
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
Dai
D
Suzuki
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.
Yoshiro
Y
Saito
Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Hidetoshi
H
Kassai
Department of Orthodontics, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
Yuki
Y
Sato
Department of Periodontology, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
Matsuo
M
Yamamoto
Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
Tatsuo
T
Shirota
Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Atsu
A
Aiba
Department of Orthodontics, School of Dentistry, Showa University, Ohta, Tokyo 145-8515, Japan.
Koutaro
K
Maki
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
Ryutaro
R
Kamijo
Cdc42; Cleft palate; Conditional knockout mice; P0-cre transgenic mice