Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect.
Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect.
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DOI：
10.1016/j.ydbio.2014.04.013
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发表时间：
2014-07-15
影响因子：
2.7
通讯作者：
Chen, YiPing
中科院分区：
文献类型：
--
作者：
He, Fenglei;Hu, Xuefeng;Xiong, Wei;Li, Lu;Lin, Lisong;Shen, Bin;Yang, Ling;Gu, Shuping;Zhang, Yanding;Chen, YiPing
先天性骨融合症是一种罕见但严重的人类先天性缺陷，其特征是下颌骨与上颌骨的骨融合。然而，由于现有动物模型的限制，人们对这种先天缺陷的遗传机制知之甚少。在这里，我们提出证据表明，神经嵴细胞中转基因Bmp4的表达导致小鼠颅面畸形，包括上颌和下颌骨发育不良之间的骨融合，类似于人类的骨融合综合征。此外，腭架的前半部分在突变体中出现于下颌弓而不是上颌骨。基因表达分析显示，在这些突变体的上颌和下颌突中，包括Hand2、Dlx2、Msx1、Barx1、Foxc2和Fgf8在内的几个面部模式基因的表达发生了改变，表明面部区域的颅神经嵴（CNC）来源细胞出现了错误的模式。然而，尽管形成了腭裂和异位软骨，但在CNC谱系中，BMP受体- ia （caBmprIa）的组成活性形式的强制表达并没有产生合颌表型，这表明增强的BMP4信号的非细胞自主作用。我们的研究表明，CNC细胞中异常的bmp4介导的信号通路导致面部骨骼和先天性骨融合的错误模式，并提示BMP信号通路的突变与人类骨融合有关。
Congenital bony syngnathia, a rare but severe human birth defect, is characterized by bony fusion of the mandible to the maxilla. However, the genetic mechanisms underlying this birth defect are poorly understood, largely due to limitation of available animal models. Here we present evidence that transgenic expression of Bmp4 in neural crest cells causes a series of craniofacial malformations in mice, including a bony fusion between the maxilla and hypoplastic mandible, resembling the bony syngnathia syndrome in humans. In addition, the anterior portion of the palatal shelves emerged from the mandibular arch instead of the maxilla in the mutants. Gene expression assays showed an altered expression of several facial patterning genes, including Hand2, Dlx2, Msx1, Barx1, Foxc2 and Fgf8, in the maxillary and mandibular processes of the mutants, indicating mis-patterned cranial neural crest (CNC) derived cells in the facial region. However, despite of formation of cleft palate and ectopic cartilage, forced expression of a constitutively active form of BMP receptor-Ia (caBmprIa) in CNC lineage did not produce the syngnathia phenotype, suggesting a non-cell autonomous effect of the augmented BMP4 signaling. Our studies demonstrate that aberrant BMP4-mediated signaling in CNC cells leads to mis-patterned facial skeleton and congenital bony syngnathia, and suggest an implication of mutations in BMP signaling pathway in human bony syngnathia.
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影响因子：
5.8
作者：
Bandyopadhyay, Amitabha;Yadav, Prem Swaroop;Prashar, Paritosh
通讯作者：
Prashar, Paritosh
DOI：
10.1002/jez.b.21205
发表时间：
2008-06-15
影响因子：
2.2
作者：
Depew, Michael J.;Compagnucci, Claudia
通讯作者：
Compagnucci, Claudia
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作者：
Boell, Louis;Pallares, Luisa F.;Tautz, Diethard
通讯作者：
Tautz, Diethard
影响因子：
4.5
作者：
Inman KE;Purcell P;Kume T;Trainor PA
通讯作者：
Trainor PA
影响因子：
1.5
作者：
Lan, Yu;Wang, Oingru;Jiang, Rulang
通讯作者：
Jiang, Rulang