Sonic hedgehog is required for neural crest-dependent patterning of the intrinsic tongue musculature
Sonic hedgehog is required for neural crest-dependent patterning of the intrinsic tongue musculature
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DOI：
10.1101/154443
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发表时间：
2017-06
期刊：
影响因子：
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通讯作者：
S. Okuhara;A. A. Birjandi-A.;H. A. Al-lami;T. Sagai;T. Amano;T. Shiroishi;Karen J. Liu;M. Cobourne;S. Iseki
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文献类型：
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作者：
S. Okuhara;A. A. Birjandi-A.;H. A. Al-lami;T. Sagai;T. Amano;T. Shiroishi;Karen J. Liu;M. Cobourne;S. Iseki
舌头是一个高度专门化的肌肉器官，对于呼吸、言语、味觉和吞咽很重要。分泌的信号分子Sonic hedgehog（Shh）从最初发育阶段开始在舌背上皮中表达。在这项研究中，我们利用了一系列的遗传学方法来调查在小鼠舌头形成的Shh的作用。Shh的时间特异性全局缺失证明了固有舌肌的正常模式和舌肌腱的建立的功能要求。这些缺陷在突变体中通过Shh顺式增强子在口咽上皮中产生特定的信号丢失。在这些突变体中，Ptch 1在潜在的颅神经嵴（CNC）衍生的间充质谱系中丢失。Shh的重要性通过在纤毛病基因Ofd1中产生组织特异性缺失得到证实，该基因转导Shh信号。这些结果揭示了Shh通过CNC衍生的间充质在中胚层内在舌肌（包括舌腱）的图案化中的作用。
The tongue is a highly specialized muscular organ important for breathing, speech, taste and swallowing. The secreted signaling molecule Sonic hedgehog (Shh) is expressed in dorsal tongue epithelium from the initial developmental stage. In this study, we utilized a series of genetic approaches to investigate the role of Shh during mouse tongue formation. Temporal-specific global deletion of Shh demonstrated a functional requirement for normal patterning of the intrinsic tongue muscles and establishment of the lingual tendon. These defects were reproduced in the mutant with a specific loss of signaling in oropharyngeal epithelium by a Shh cis-enhancer. In these mutants, Ptch1 was lost in the underlying cranial neural crest (CNC)-derived mesenchymal lineage. The importance of Shh was confirmed by generating tissue-specific deletions in the ciliopathy gene Ofd1, which transduces Shh signaling. These results revealed Shh roles in patterning of the mesodermal intrinsic tongue muscles through CNC-derived mesenchyme, including the lingual tendon.