Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.
Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.
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DOI：
10.1371/journal.pone.0066107
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Li L;Wang Y;Lin M;Yuan G;Yang G;Zheng Y;Chen Y
BMP受体Ia（BMPRIa）介导的信号传导在颅面器官（包括牙齿和腭）发育中的重要性已经在几种功能丧失的小鼠模型中以及通过其与青少年息肉综合征和人类面部缺陷相关的突变得到充分阐明。在这项研究中，我们采取了一种功能获得的方法，以进一步解决的作用，BMPR-IA介导的信号在间充质室在牙齿和腭发育。我们产生的转基因小鼠表达的组成型活性形式的BmprIa（caBmprIa）的颅神经嵴（CNC）细胞，有助于牙齿和腭间充质。在CNC细胞中携带增强的BMPRIa介导信号的小鼠表现出完全的腭裂和延迟的牙源性分化。我们发现，腭裂缺陷的转基因动物是由于改变细胞增殖率在前腭间充质和延迟腭隆起与异位软骨形成的后部。尽管在牙齿间充质中BMP信号传导的活性增强，但转基因小鼠的牙齿发育和图案形成似乎正常，除了延迟的牙源性分化。这些数据支持这样的假设，即精细调节的BMPRIa介导的信号传导水平对于正常的腭和牙齿发育是必不可少的。
The importance of BMP receptor Ia (BMPRIa) mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa) in cranial neural crest (CNC) cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.
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影响因子：
3.5
作者：
Menko, F. H.;Kneepkens, C. M. F.;Sistermans, E. A.
通讯作者：
Sistermans, E. A.
小鼠上门牙的早期发育需要 Noggin
影响因子：
7.6
作者：
Hu, X.;Wang, Y.;Chen, Y. P.
通讯作者：
Chen, Y. P.
DOI：
10.1359/jbmr.091103
发表时间：
2010-05
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Huang X;Xu X;Bringas P Jr;Hung YP;Chai Y
通讯作者：
Chai Y
影响因子：
3.6
作者：
Hosoya, Akihiro;Kim, Ji-Youn;Jung, Han-Sung
通讯作者：
Jung, Han-Sung
影响因子：
2.7
作者：
Baek JA;Lan Y;Liu H;Maltby KM;Mishina Y;Jiang R
通讯作者：
Jiang R