Specific inactivation of Twist1 in the mandibular arch neural crest cells affects the development of the ramus and reveals interactions with hand2.

Specific inactivation of Twist1 in the mandibular arch neural crest cells affects the development of the ramus and reveals interactions with hand2.
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DOI:
10.1002/dvdy.23776
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发表时间:
2012-05
影响因子:
2.5
通讯作者:
Ruest, L. Bruno
Ruest, L. Bruno
中科院分区:
生物学3区
文献类型:
--
作者:
Zhang, Yanping;Blackwell, Evan L.;McKnight, Mitchell T.;Knutsen, Gregory R.;Vu, Wendy T.;Ruest, L. Bruno

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基础螺旋环阻滞(bHLH)转录因子Twist 1在神经嵴细胞形成、迁移和存活中发挥重要作用,并与人类颅缝Saethre-Chotzen综合征相关。然而,它在下颌骨发育过程中的功能,当它可能与其他bHLH转录因子如Hand 2相互作用时,是未知的,因为Twist 1无效突变的纯合子小鼠在早期胚胎发育中死亡。为了确定Twist 1在下颌骨发育过程中的作用,我们使用了Hand 2-Cre转基因有条件地将该基因转移到下颌咽弓神经嵴细胞中。突变小鼠表现出一系列颅面异常,包括下颌骨发育不全,中耳发育改变和腭裂。看来,Twist 1是必不可少的生存的神经嵴细胞参与的下颌枝元素的发展。Twist 1通过参与形成釉质结所需的相互信号传导,在磨牙发育和牙尖形成中发挥作用。这个基因也需要控制下颌骨的骨化,这是一个与Hand 2共享的冗余角色。Twist 1和Hand 2对下颌骨的近远侧模式和发育以及骨化至关重要。
The basic Helix-Loop-Helix (bHLH) transcription factor Twist1 fulfills an essential function in neural crest cell formation, migration and survival and is associated with the craniosynostic Saethre-Chotzen syndrome in humans. However, its functions during mandibular development, when it may interact with other bHLH transcription factors like Hand2, are unknown since mice homozygous for the Twist1 null mutation die in early embryogenesis. To determine the role of Twist1 during mandibular development, we used the Hand2-Cre transgene to conditionally inactivate the gene in the neural crest cells populating the mandibular pharyngeal arch. The mutant mice exhibited a spectrum of craniofacial anomalies, including mandibular hypoplasia, altered middle ear development, and cleft palate. It appears that Twist1 is essential for the survival of the neural crest cells involved in the development of the mandibular ramal elements. Twist1 plays a role in molar development and cusp formation by participating in the reciprocal signaling needed for the formation of the enamel knot. This gene is also needed to control the ossification of the mandible, a redundant role shared with Hand2. Twist1, along with Hand2, is essential for the proximo-distal patterning and development of the mandible and ossification.
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