The Role of Twist During Palate Development

The Role of Twist During Palate Development
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DOI:
10.1002/dvdy.21627
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发表时间:
2008-10-01
影响因子:
2.5
通讯作者:
Svoboda, Kathy K. H.
Svoboda, Kathy K. H.
中科院分区:
生物学3区
文献类型:
--
作者:
Yu, Wenli;Kamara, Harold;Svoboda, Kathy K. H.

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在腭裂发生中,当腭部融合时,MEE(内侧边缘上皮)细胞消失。我们假设MEE细胞经历了EMT(上皮-间充质转化)以实现间充质融合。TWIST在肿瘤转移的EMT中起着重要作用。本研究的目的是分析腭裂融合过程中的扭转功能。在融合前,Twist蛋白在体内和体外均在腭架和MEE中表达。转化生长因子β3处理后3h和6h,鸡上颌骨中的twist基因表达增加。用200 nM的Twist siRNA处理培养的腭架后,腭裂融合率降低,P-catenin的亚细胞定位发生改变。经转化生长因子β3中和抗体或磷脂酰肌醇-3激酶(PI-3K)特异性抑制剂LY294002处理后,腭部牙槽突起TWIST基因表达减少。综上所述,在腭裂融合过程中,Twist位于转化生长因子β3和PI-3K通路的下游。然而,使用siRNA降低Twist并不能完全阻止腭部融合,这表明Twist的功能可能被其他转录因子复制。《发展动力学》237:2716-2725,2008。(C)2008年Wiley-Liss,Inc.
In palatogenesis, the MEE (Medial Edge Epithelium) cells disappear when palates fuse. We hypothesize that the MEE cells undergo EMT (Epithelial-Mesenchymal Transition) to achieve mesenchyme confluence. Twist has an important role in EMT for tumor metastasis. The purpose of this study was to analyze Twist function during palatal fusion. Twist protein was expressed in palatal shelves and MEE both in vivo and in vitro just prior to fusion. Twist mRNA increased in chicken palates 3 and 6 hr after TGF beta 3 treatment. Palatal fusion was decreased when cultured palatal shelves were treated with 200 nM Twist siRNA and the subcellular localization of P-catenin was altered. Twist mRNA decreased in palatal shelves treated with TGF beta 3 neutralizing antibody or LY294002, a specific phosphatidylinositol-3 kinase (PI-3K) inhibitor. In summary, Twist is downstream of TGF beta 3 and PI-3K pathways during palatal fusion. However, decreasing Twist with siRNA did not completely block palate fusion, indicating that the function of Twist may be duplicated by other transcription factors. Developmental Dynamics 237:2716-2725, 2008. (C) 2008 Wiley-Liss, Inc.