Gli3-Deficient Mice Exhibit Cleft Palate Associated With Abnormal Tongue Development
Gli3-Deficient Mice Exhibit Cleft Palate Associated With Abnormal Tongue Development
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DOI：
10.1002/dvdy.21714
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发表时间：
2008-10-01
影响因子：
2.5
通讯作者：
Chiang, Chin
中科院分区：
文献类型：
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作者：
Huang, Xi;Goudy, Steven L.;Chiang, Chin
腭裂的发生依赖于腭架的适当生长、抬高和融合，这些过程中的异常可能会导致腭裂。我们观察到在缺乏Gli3的小鼠中，腭裂的发生率很高，Gli3以其在缺少Shh信号的情况下作为抑制者的作用而闻名。与目前的几种腭裂小鼠模型相比，Gli3(-/-)小鼠的Meckel‘s软骨延伸、脑神经脊移、腭架增殖、细胞凋亡以及由Shh、BMP、FGF和转化生长因子β介导的关键信号成分似乎没有受到影响。Gli3(-/-)小鼠的腭裂一直与舌部异常有关，例如舌头不能压平和位置不正确，这意味着Gli3和正常的舌头形态发生在适时的腭架抬高和连接方面发挥了关键作用。此外，在没有舌头的滚筒培养中生长的Gli3(-/-)腭架可以融合，这表明异常的舌头可能是Gli3(-/-)突变体连接腭架的障碍。《发展动力学》237：3079-3087,2008。(C)2008年Wiley-Liss，Inc.
Palatogenesis depends on appropriate growth, elevation, and fusion of the palatal shelves and aberration in these processes can lead to palatal clefting. We observed a high incidence of palate clefting in mice deficient in Gli3, known for its role as a repressor in the absence of Shh signaling. In contrast with several current mouse models of cleft palate, Meckel's cartilage extension, cranial neural crest migration, palatal shelf proliferation, apoptosis, and key signaling components mediated by Shh, Bmp, Fgf, and Tgf beta, appeared unaffected in Gli3(-/-) mice. Palatal clefting in Gli3(-/-) mice was consistently associated with tongue abnormalities such as failure to flatten and improper positioning, implicating a critical role of Gli3 and normal tongue morphogenesis for timely palatal shelf elevation and joining. Furthermore, Gli3(-/-) palatal shelves grown in roller cultures without tongue can fuse suggesting that the abnormal tongue is likely an impediment for palatal shelf joining in Gli3(-/-) mutants. Developmental Dynamics 237:3079-3087, 2008. (c) 2008 Wiley-Liss, Inc.