Contrasting expression of canonical Wnt signaling reporters TOPGAL, BATGAL and Axin2(LacZ) during murine lung development and repair.

Contrasting expression of canonical Wnt signaling reporters TOPGAL, BATGAL and Axin2(LacZ) during murine lung development and repair.
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DOI:
10.1371/journal.pone.0023139
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Bellusci S
Bellusci S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Al Alam D;Green M;Tabatabai Irani R;Parsa S;Danopoulos S;Sala FG;Branch J;El Agha E;Tiozzo C;Voswinckel R;Jesudason EC;Warburton D;Bellusci S

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规范的Wnt信号通过调节早期祖细胞的命运在肺器官发生和修复中发挥多种作用:规范的Wnt报告小鼠、TOPGAL、BATGAL和Axin2LacZ加强了研究。尽管被广泛使用,但目前尚不清楚这些记者是否传达了关于规范WNT信号的相同信息。因此,我们比较了这些报告小鼠在整个胚胎和分离的产前肺中规范的Wnt信号中的β-半乳糖苷酶的表达模式。为了确定修复过程中的表达是否会进一步变化,我们分析了萘损伤后肺组织中β-半乳糖苷酶的表达。我们的数据显示了报告老鼠之间的重要差异。虽然TOPGAL和BATGAL细胞系在早期肺上皮细胞中显示WNT信号良好,但BATGAL在胚胎晚期和成年肺中的表达显著降低。相反,Axin2LacZ在胚胎肺间充质和上皮细胞中持续表达。修复三天后,BATGAL在支气管上皮中被诱导表达,TOPGAL(已经在没有损伤的情况下强烈表达)被诱导表达。Axin2LacZ在损伤肺的支气管上皮中表达增加。有趣的是,TOPGAL和Axin2LacZ在修复过程中都在支气管周围的平滑肌细胞中上调。因此,Wnt报告线的最佳选择取决于是否正在比较肺上皮或间充质中规范的Wnt信号报告的上调或下调。
Canonical Wnt signaling plays multiple roles in lung organogenesis and repair by regulating early progenitor cell fates: investigation has been enhanced by canonical Wnt reporter mice, TOPGAL, BATGAL and Axin2LacZ. Although widely used, it remains unclear whether these reporters convey the same information about canonical Wnt signaling. We therefore compared beta-galactosidase expression patterns in canonical Wnt signaling of these reporter mice in whole embryo versus isolated prenatal lungs. To determine if expression varied further during repair, we analyzed comparative pulmonary expression of beta-galactosidase after naphthalene injury. Our data show important differences between reporter mice. While TOPGAL and BATGAL lines demonstrate Wnt signaling well in early lung epithelium, BATGAL expression is markedly reduced in late embryonic and adult lungs. By contrast, Axin2LacZ expression is sustained in embryonic lung mesenchyme as well as epithelium. Three days into repair after naphthalene, BATGAL expression is induced in bronchial epithelium as well as TOPGAL expression (already strongly expressed without injury). Axin2LacZ expression is increased in bronchial epithelium of injured lungs. Interestingly, both TOPGAL and Axin2LacZ are up regulated in parabronchial smooth muscle cells during repair. Therefore the optimal choice of Wnt reporter line depends on whether up- or down-regulation of canonical Wnt signal reporting in either lung epithelium or mesenchyme is being compared.
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