Cdc42 is crucial for facial and palatal formation during craniofacial development.
Cdc42 is crucial for facial and palatal formation during craniofacial development.
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DOI：
10.1016/j.bonr.2016.01.001
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发表时间：
2016-12
期刊：
影响因子：
2.5
通讯作者：
Kamijo R
中科院分区：
文献类型：
--
作者：
Oshima-Nakayama M;Yamada A;Kurosawa T;Aizawa R;Suzuki D;Saito Y;Kassai H;Sato Y;Yamamoto M;Shirota T;Aiba A;Maki K;Kamijo R
颅面畸形具有多因素的病因，如腭裂和面部畸形，是人类最常见的先天性出生缺陷。其发病机制常与颅神经嵴（CNC）细胞有关。在CNC细胞迁移过程中，细胞形状和形成的变化以及亚细胞结构（如丝状足和板足）的维持依赖于Rho家族小gtpase的复杂功能，后者是肌动蛋白细胞骨架组织的调节剂。Cdc42是小gtp酶Rho家族的一员，在各种组织的器官发生中起着关键作用。为了研究Cdc42在颅面发育过程中的生理功能，我们培育了cnc来源的细胞特异性灭活Cdc42突变小鼠（Cdc42fl/fl;P0-cre）。大部分Cdc42fl/fl；新生儿出生时是可以存活的，尽管他们看起来比较虚弱，胃里没有牛奶，并且在几天内全部死亡。他们脸短，颅内出血，颅骨异常钙化。Cdc42fl / fl;新生儿也表现为腭裂，由于腭裂闭合过程中腭架延伸失败，导致第二腭没有融合。在颅面发育过程中，Cdc42对面部和腭的形成至关重要。产生颅神经嵴来源的细胞特异性Cdc42缺失突变小鼠。Cdc42突变小鼠被发现有腭裂。在Cdc42突变小鼠中腭架延伸失败。
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. Cranial neural crest-derived cell-specific Cdc42 deletion mutant mice were generated. Cdc42 mutant mice were found to have a cleft palate. Palatal shelf elongation failed in Cdc42 mutant mice.