Oshima-Nakayama Mutsuko, Yamada Atsushi, Kurosawa Tamaki, Aizawa Ryo, Suzuki Dai, Saito Yoshiro, Kassai Hidetoshi, Sato Yuki, Yamamoto Matsuo, Shirota Tatsuo, Aiba Atsu, Maki Koutaro, Kamijo Ryutaro
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.
Department of Biochemistry, School of Dentistry, Showa University, Shinagawa, Tokyo 142-8555, Japan.
Bone Rep. 2016 Jan 8;5:1-6. doi: 10.1016/j.bonr.2016.01.001. eCollection 2016 Dec.
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 ( ;). Most of the ; 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. ; 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.
诸如腭裂和面部畸形等具有多因素病因的颅面畸形，是人类中最常见的先天性出生缺陷之一。它们的发病机制通常与颅神经嵴（CNC）细胞有关。在CNC细胞迁移过程中，细胞形状和形态的变化以及亚细胞结构（如丝状伪足和片状伪足）的维持，取决于Rho家族小GTP酶的复杂功能，这些酶是肌动蛋白细胞骨架组织的调节因子。Cdc42是Rho家族小GTP酶的成员之一，已知在各种组织的器官发生中起关键作用。为了研究Cdc42在颅面发育过程中的生理功能，我们构建了CNC来源的细胞特异性失活Cdc42突变小鼠（ ； ）。大多数 ； 新生小鼠出生时是存活的，尽管它们看起来较弱且胃中没有乳汁，并且全部在几天内死亡。它们面部短小且颅内出血，颅骨钙化异常。 ； 新生小鼠还表现出腭裂，并且由于在腭部闭合过程中腭突伸长失败，继发腭没有融合。Cdc42在颅面发育过程中对面部和腭部的形成至关重要。
