Ablation of lung epithelial cells deregulates FGF-10 expression and impairs lung branching morphogenesis.
Ablation of lung epithelial cells deregulates FGF-10 expression and impairs lung branching morphogenesis.
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DOI：
10.1002/ar.20799
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发表时间：
2009-01
影响因子：
2
通讯作者：
Vu, Thiennu H.
中科院分区：
文献类型：
--
作者：
Kim, Namjin;Yamamoto, Hiroaki;Pauling, Michelle Haynes;Lorizio, Walter;Vu, Thiennu H.
在器官发生过程中，上皮-间充质相互作用对组织模式的形成至关重要。远端肺上皮及其邻近的间充质组成了调节肺分支形态发生的上皮-间充质信号单元。组织重组实验已经证明了间充质信号在诱导肺上皮分化和分支中的重要性，但上皮在调节间充质信号中的作用尚未得到很好的表征。利用转基因小鼠，我们在肺发育过程中通过诱导表面活性剂蛋白C （SP-C）启动子下组成型活性促凋亡蛋白Bax的表达，切除了远端肺上皮细胞。我们发现上皮细胞消融导致肺分支形态发生受损，并在成人中发展为肺气肿。成纤维细胞生长因子10 （Fgf-10）的间充质表达被破坏并失去其局部模式，而Fgf-10严格的时空表达对正常的肺分支形态形成至关重要。有趣的是，已知调节Fgf-10表达的上皮基因sonic hedgehog （Shh）的表达没有变化，这表明存在其他调节间充质Fgf-10表达的远端上皮信号。我们认为，在肺发育过程中，表达远端SP-C的肺上皮细胞为下调远端间质中Fgf-10的表达提供了必要的信号。
Epithelial-mesenchymal interactions are essential for tissue patterning during organogenesis. Distal lung epithelium and its adjacent mesenchyme comprise the epithelial-mesenchymal signaling unit that regulates lung branching morphogenesis. Tissue recombination experiments have demonstrated the importance of mesenchymal signals in inducing lung epithelial differentiation and branching, but the role of the epithelium in regulating mesenchymal signals has not been well characterized. Using transgenic mice, we ablated distal lung epithelial cells during lung development by inducing the expression of a constitutively active proapoptotic Bax protein under the surfactant protein C (SP-C) promoter. We found that epithelial cell ablation results in impaired lung branching morphogenesis, which progresses to emphysematous airspaces in the adults. Mesenchymal expression of fibroblast growth factor 10 (Fgf-10), whose strict spatial and temporal expression is critical for proper lung branching morphogenesis, is disrupted and loses its localized pattern. Interestingly, the expression of sonic hedgehog (Shh), an epithelial gene known to modulate Fgf-10 expression, is unchanged, indicating the existence of other distal epithelial signals that regulate mesenchymal Fgf-10 expression. We propose that distal SP-C expressing lung epithelial cells provide essential signals for the downregulation of Fgf-10 expression in the distal mesenchyme during lung development.
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影响因子：
9.2
作者：
Pepicelli, CV;Lewis, PM;McMahon, AP
通讯作者：
McMahon, AP
影响因子：
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作者：
WESSELLS, NK
通讯作者：
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作者：
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作者：
Min, HS;Danilenko, DM;Simonet, WS
通讯作者：
Simonet, WS