The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components
The absence of SOX2 in the anterior foregut alters the esophagus into trachea and bronchi in both epithelial and mesenchymal components
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DOI：
10.1242/bio.048728
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发表时间：
2019-08
期刊：
影响因子：
2.4
通讯作者：
Machiko Teramoto;Ryo Sugawara;Katsura Minegishi;M. Uchikawa;T. Takemoto;A. Kuroiwa;Y. Ishii;H. Kondoh
中科院分区：
文献类型：
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作者：
Machiko Teramoto;Ryo Sugawara;Katsura Minegishi;M. Uchikawa;T. Takemoto;A. Kuroiwa;Y. Ishii;H. Kondoh
在小鼠胚胎的前前肠（AFG）中，转录因子SOX 2在食管上皮和呼吸器官近端分支（包括气管和支气管）中表达，而NKX2.1仅在呼吸器官的上皮中表达。以前的研究使用亚型Sox 2等位基因表明，减少SOX 2的表达导致食管上皮显示一些呼吸器官的特征。在本研究中，我们产生了具有AFG特异性SOX 2缺陷的小鼠胚胎。在没有SOX 2表达的情况下，单个表达NKX2.1的上皮管连接咽和胃，并且一对支气管在管的中间发育。NKX2.1和SOX 9的表达模式显示，SOX 2缺陷型AFG上皮管的前半部分和后半部分分别具有气管和支气管的特征。此外，我们发现，围绕SOX 2缺陷NKX2.1表达上皮管的间充质组织改变为前半部分和后半部分气管和支气管周围的间充质组织，如平滑肌细胞和SOX 9表达细胞的排列以及Wnt 4（食管特异性）、Tbx 4（呼吸器官特异性）和Hoxb 6（远端支气管特异性）的表达所示。间充质来源的信号传导对AFG上皮特化的早期阶段的影响已经被指出。我们的研究表明了相反的趋势，即上皮组织特异性导致间充质组织的一致变化，表明上皮-间充质相互作用的相互作用。总结：响应于当SOX 2失活时发生的从食管到气管/支气管的上皮特征的变化，周围的间充质组织也相应地在所有轴向水平上改变它们的特征。
ABSTRACT In the anterior foregut (AFG) of mouse embryos, the transcription factor SOX2 is expressed in the epithelia of the esophagus and proximal branches of respiratory organs comprising the trachea and bronchi, whereas NKX2.1 is expressed only in the epithelia of respiratory organs. Previous studies using hypomorphic Sox2 alleles have indicated that reduced SOX2 expression causes the esophageal epithelium to display some respiratory organ characteristics. In the present study, we produced mouse embryos with AFG-specific SOX2 deficiency. In the absence of SOX2 expression, a single NKX2.1-expressing epithelial tube connected the pharynx and the stomach, and a pair of bronchi developed in the middle of the tube. Expression patterns of NKX2.1 and SOX9 revealed that the anterior and posterior halves of SOX2-deficient AFG epithelial tubes assumed the characteristics of the trachea and bronchus, respectively. In addition, we found that mesenchymal tissues surrounding the SOX2-deficient NKX2.1-expressing epithelial tube changed to those surrounding the trachea and bronchi in the anterior and posterior halves, as indicated by the arrangement of smooth muscle cells and SOX9-expressing cells and by the expression of Wnt4 (esophagus specific), Tbx4 (respiratory organ specific), and Hoxb6 (distal bronchus specific). The impact of mesenchyme-derived signaling on the early stage of AFG epithelial specification has been indicated. Our study demonstrated an opposite trend where epithelial tissue specification causes concordant changes in mesenchymal tissues, indicating a reciprocity of epithelial-mesenchymal interactions. Summary: In response to the change in the epithelial characteristics from esophagus to trachea/bronchus that happens when SOX2 is inactivated, surrounding mesenchymal tissues also change their characteristics accordingly at all axial levels.