Treacher Collins syndrome: unmasking the role of Tcof1/treacle.
Treacher Collins syndrome: unmasking the role of Tcof1/treacle.
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DOI：
10.1016/j.biocel.2008.10.026
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发表时间：
2009-06
影响因子：
4
通讯作者：
Trainor, Paul A.
中科院分区：
文献类型：
--
作者：
Sakai, Daisuke;Trainor, Paul A.
Treacher柯林斯综合征（TCS）是一种罕见的以严重颅面畸形为特征的先天性出生障碍。该综合征与TCOF1基因突变有关，TCOF1基因编码一种被称为糖浆的假定核仁磷蛋白。通过突变小鼠同源物Tcof1产生的严重形式的TCS的动物模型最近揭示了对TCS的病因和发病机制的重要见解。在TCS个体的早期胚胎发生过程中，过度的神经上皮细胞凋亡减少了神经嵴细胞的产生。神经嵴细胞是一种可迁移的干细胞和祖细胞群，其产生头部的大部分组织，包括大部分骨、软骨和结缔组织。据推测，Tcof1的突变破坏核糖体生物合成的程度是不足以满足神经上皮细胞和神经嵴细胞的增殖需要。这导致p53依赖性凋亡途径的核仁应激激活，从而诱导神经上皮细胞死亡。然而，有趣的是，p53活性的化学和遗传抑制可以阻断Tcof1突变小鼠中的细胞凋亡波并预防颅面异常[Jones NC，林恩ML，Gaudenz K，Sakai D，Aoto K，Rey JP，et al. Prevention of the neurocristopathy Treacher柯林斯综合征通过抑制p53功能。Nat Med 2008; 14：125 - 33]。这些发现揭示了新的潜在的治疗途径，不仅预防TCS，但也有其他先天性颅面疾病，共享一个类似的病因和发病机制。
Treacher Collins syndrome (TCS) is a rare congenital birth disorder characterized by severe craniofacial defects. The syndrome is associated with mutations in the TCOF1 gene which encodes a putative nucleolar phosphoprotein known as treacle. An animal model of the severe form of TCS, generated through mutation of the mouse homologue Tcof1 has recently revealed significant insights into the etiology and pathogenesis of TCS. During early embryogenesis in a TCS individual, an excessive degree of neuroepithelial apoptosis diminishes the generation of neural crest cells. Neural crest cells are a migratory stem and progenitor cell population that generates most of the tissues of the head including much of the bone, cartilage and connective tissue. It has been hypothesized that mutations in Tcof1 disrupt ribosome biogenesis to a degree that is insufficient to meet the proliferative needs of the neuroepithelium and neural crest cells. This causes nucleolar stress activation of the p53-dependent apoptotic pathway which induces neuroepithelial cell death. Interestingly however, chemical and genetic inhibition of p53 activity can block the wave of apoptosis and prevent craniofacial anomalies in Tcof1 mutant mice [Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 2008;14:125–33]. These findings shed new light on potential therapeutic avenues for the prevention of not only TCS but also other congenital craniofacial disorders which share a similar etiology and pathogenesis.
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影响因子：
2.5
作者：
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通讯作者：
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DOI：
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发表时间：
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