The Epithelial Expressions of YAP and TAZ are Sequentially Required in Lung Development.
The Epithelial Expressions of YAP and TAZ are Sequentially Required in Lung Development.
复制标题
YAP 和 TAZ 的上皮表达是肺发育中顺序需要的。
DOI：
--
复制
发表时间：
2020
影响因子：
6.4
通讯作者：
T. Nagase
中科院分区：
文献类型：
--
作者：
Hideaki Isago;A. Mitani;Yu Mikami;Masafumi Horie;H. Urushiyama;Ryuji Hamamoto;Y. Terasaki;T. Nagase
基本原理
带有PDZ结合基序的转录共激活因子(TAZ)和YAP是河马途径的关键分子。最近的研究表明，这些分子在肺发育中是必不可少的；然而，涉及这些分子的确切信号级联以及它们在肺发育过程中的作用差异仍不清楚。
目标
我们的目标是使用肺上皮细胞特异性的TAZ和YAP条件基因敲除小鼠来研究YAP和TAZ的功能。
方法
我们建立了肺上皮细胞特异性的TAZ和YAP条件基因敲除小鼠，并研究了YAP和TAZ在肺发育中的作用。
测量方法和主要结果
小鼠肺上皮细胞中选择性的TAZ缺乏症导致成人肺泡化异常，类似肺气肿，而YAP缺乏症在胚胎期引起支气管形态发生的破坏。我们报告了TAZ和YAP在肺中的顺序表达，这可以解释它们不同的表型。此外，我们还报道YAP刺激Sonic hedgehog(Shh)的表达并调节成纤维细胞生长因子-SHH反馈环，从而促进正常的支气管形态发生。我们还发现，转化生长因子-Β刺激诱导了肺上皮细胞Shh的表达，TAZ和YAP在这一新的途径中都是必不可少的。
结论
我们的结果为肺发育的分子机制提供了新的见解，并有助于更好地理解TAZ和YAP的特征。
RATIONALE
Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP) are key molecules of the Hippo pathway. Recent studies revealed that these molecules are essential in lung development; however, the precise signaling cascade involving these molecules and the differences in their role during lung development remain unknown.
OBJECTIVES
We aimed to investigate YAP and TAZ functions using lung epithelial-specific Taz and Yap conditional knockout mice.
METHODS
We generated lung epithelial-specific Taz and Yap conditional knockout mice and investigated the functions of YAP and TAZ in lung development.
MEASUREMENTS AND MAIN RESULTS
Selective TAZ deficiency in mouse lung epithelial cells resulted in abnormal alveolarization, which mimics lung emphysema, in adults, whereas YAP deficiency caused disruption of bronchial morphogenesis during the embryonic stage. We report that TAZ and YAP are sequentially expressed in the lung, and that this could explain their different phenotypes. Furthermore, we report that YAP stimulates Sonic hedgehog (Shh) expression and regulates the FGF-SHH feedback loop, thereby contributing to normal bronchial morphogenesis. We also found that TGF-Β stimulation induced Shh expression in the lung epithelial cells, and both TAZ and YAP are essential in this novel pathway.
CONCLUSIONS
Our results provide a novel insight into the molecular mechanisms underlying lung development and contributes to a better understanding of the characteristics of TAZ and YAP.
登录
查看更多内容
影响因子：
4.6
作者：
S. Bellusci;Y. Furuta;M. Rush;R. Henderson;G. Winnier;B. Hogan
通讯作者：
S. Bellusci;Y. Furuta;M. Rush;R. Henderson;G. Winnier;B. Hogan
影响因子：
11.8
作者：
Mahoney JE;Mori M;Szymaniak AD;Varelas X;Cardoso WV
通讯作者：
Cardoso WV
影响因子：
11.8
作者：
Herriges JC;Verheyden JM;Zhang Z;Sui P;Zhang Y;Anderson MJ;Swing DA;Zhang Y;Lewandoski M;Sun X
通讯作者：
Sun X
DOI：
10.1007/978-1-59745-019-5_5
发表时间：
2010
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.8
作者：
Pan, Duojia
通讯作者：
Pan, Duojia