Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice.
Augmented Indian hedgehog signaling in cranial neural crest cells leads to craniofacial abnormalities and dysplastic temporomandibular joint in mice.
复制标题
DOI：
10.1007/s00441-015-2306-5
复制
发表时间：
2016-04
影响因子：
3.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Yang L;Gu S;Ye W;Song Y;Chen Y
大量研究已明确印度刺猬（Ihh）信号在四肢骨骼发育中的关键作用以及Ihh在颞下颌关节（TMJ）形成中的重要功能。在这项研究中，我们探究了增强的Ihh信号在颞下颌关节发育中的影响。我们采用转基因功能获得性方法，利用条件性Ihh转基因等位基因和Wnt1 - Cre等位基因在颅神经嵴（CNC）细胞中过表达Ihh。我们发现Wnt1 - Cre介导的Ihh在CNC谱系中的组织特异性过表达导致严重的颅面异常，包括唇裂/腭裂、脑膨出、无眼、小颌畸形以及颞下颌关节发育缺陷。在突变的颞下颌关节中，关节窝完全缺失，而髁突和关节盘看起来相对正常，但软骨细胞分化稍有延迟。因此，我们的研究结果表明，增强的Ihh信号对颅面发育有害，并且精细调节的Ihh信号对颞下颌关节的形成至关重要。我们的结果还提供了额外的证据，证明髁突和关节盘的发育与关节窝无关。
Extensive studies have pinpointed the crucial role of Indian hedgehog (Ihh) signaling in the development of the appendicular skeleton and the essential function of Ihh in the formation of the temporomandibular joint (TMJ). In this study, we have investigated the effect of augmented Ihh signaling in TMJ development. We took a transgenic gain-of-function approach by overexpressing Ihh in the cranial neural crest (CNC) cells using a conditional Ihh transgenic allele and the Wnt1-Cre allele. We found that Wnt1-Cre-mediated tissue-specific overexpression of Ihh in the CNC lineage caused severe craniofacial abnormalities, including cleft lip/palate, encephalocele, anophthalmos, micrognathia, and defective TMJ development. In the mutant TMJ, the glenoid fossa was completely absent, whereas the condyle and the articular disc appeared relatively normal with slightly delayed chondrocyte differentiation. Our findings thus demonstrate that augmented Ihh signaling is detrimental to craniofacial development, and that finely tuned Ihh signaling is critical for TMJ formation. Our results also provide additional evidence that the development of the condyle and articular disc is independent of the glenoid fossa.