Foxc2 influences alveolar epithelial cell differentiation during lung development
Foxc2 influences alveolar epithelial cell differentiation during lung development
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Foxc2影响肺发育过程中的肺泡上皮细胞分化
DOI：
10.1111/dgd.12368
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发表时间：
2017
影响因子：
2.5
通讯作者：
Jun Tamaoki
中科院分区：
文献类型：
--
作者：
Mayoko Tsuji;Masae Morishima;Kazuhiko Shimizu;Shunichi Morikawa;Mikael Heglind;Sven Enerback;Taichi Ezaki;Jun Tamaoki
FOXC 2是一个叉头转录因子，是先天性心脏病、双趾水肿综合征和黄指甲综合征的候选基因，但目前还没有关于FOXC 2与肺发育的相关报道。我们在研究心脏发育过程中发现了Foxc 2基因敲除胚胎的肺部异常。本研究的目的是使用ICR‐ Foxc 2敲除肺阐明肺发育期间的形态学特征。从Foxc 2 +/−小鼠交配中获得胚胎10.5-18.5天的突变胎儿，然后进行分析。值得注意的是，Foxc 2敲除的肺似乎是实质性的，并且比野生型同窝仔的肺小得多。在Foxc 2基因敲除小鼠中，毛细血管床一直远离肺泡上皮，直到晚期，每个肺泡祖细胞中的2型肺泡细胞数量较低，Foxc 2基因敲除小鼠中的1型肺泡细胞较厚。相比之下，Foxc 2表达仅在E10.5的肺芽间充质中检测到，并且在E11.5的Foxc 2-LacZknockin小鼠中消失。E11.5肺组织中Lef 1的表达明显受到抑制。提示Foxc 2基因敲除小鼠的异常可能与肺泡上皮细胞分化不良、毛细血管内皮细胞-肺泡上皮细胞途径以及淋巴管畸形有关。本文首次报道Foxc 2与肺发育的关系。该动物模型为阐明肺的发育机制和呼吸系统疾病的病因提供了重要线索。
FOXC2, a forkhead transcriptional factor, is a candidate gene for congenital heart diseases and lymphedema‐distichiasis syndrome and yellow nail syndrome; however, there are no reports onFoxc2and the development of the lung. We have identified lung abnormalities inFoxc2‐knockout embryos during investigation of cardiac development. The aim of this study was to clarify the morphological characteristics during lung development using ICR‐Foxc2knockout lungs. Mutant fetuses at embryonic days 10.5–18.5 were obtained from mating ofFoxc2+/−mice and then analyzed. Notably,Foxc2‐knockout lungs appeared parenchymatous and much smaller than those of the wild‐type littermates. In theFoxc2knockout lungs, the capillary beds remained distant from the alveolar epithelium until the late stages, the number of type2 alveolar cells per alveolar progenitor cell was lower and the type1 alveolar cells were thicker inFoxc2knockout mice. In contrast,Foxc2expression was only detected in the mesenchyme of the lung buds at E10.5, and it disappeared at E11.5 inFoxc2‐LacZknockin mice. Furthermore, the expression of Lef1 was significantly inhibited in E11.5 lungs. All of these results suggest that the abnormalities inFoxc2knockout mice may involve maldifferentiation of alveolar epithelial cells and capillary vessel endothelial‐alveolar epithelial approach as well as lymph vessel malformation. This is the first report about relationship betweenFoxc2and lung development. This animal model might provide an important clue for elucidating the mechanism of lung development and the cause of respiratory diseases.