Laboratory of Developmental Biology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
PLoS One. 2012;7(4):e35362. doi: 10.1371/journal.pone.0035362. Epub 2012 Apr 13.
Transgenic Keratin14-rtTA-PTR mice specifically express Keratin14 (K14) in the tongue epithelia, as well as co-express EGFP and the dominant negative ΔTgfbr2 genes upon treatment with Doxycycline (Dox). As TGF-β signaling negatively regulates the stem cell cycle and proliferation, its disruption by Dox induction in these transgenic mice shortens the cell cycle and allows observation of the final fate of those mutated cell lineages within a short period of time. Here, we used inducible transgenic mice to track the K14+ cells through the cell migration stream by immunohistochemical an immunofluorescent imaging. We showed that these cells have different development patterns from the tip to posterior of the tongue, achieved presumably by integrating positional information from the microenvironment. The expression of the K14 gene was variable, depending on the location of the tongue and papillae. Disruption of TGF-β signaling in K14+ progenitor cells resulted in proliferation of stem cell pools.
转基因 Keratin14-rtTA-PTR 小鼠在舌上皮组织中特异性表达 Keratin14（K14），并且在给予强力霉素（Dox）处理时共同表达 EGFP 和显性负ΔTgfbr2 基因。由于 TGF-β 信号通路负调控干细胞周期和增殖，因此在这些转基因小鼠中，通过 Dox 诱导破坏 TGF-β 信号通路会缩短细胞周期，并允许在短时间内观察到这些突变细胞谱系的最终命运。在这里，我们使用可诱导的转基因小鼠通过免疫组织化学和免疫荧光成像来追踪 K14+细胞通过细胞迁移流。我们表明，这些细胞从舌的尖端到后部具有不同的发育模式，可能是通过整合来自微环境的位置信息来实现的。K14 基因的表达因舌和乳头的位置而异。在 K14+祖细胞中破坏 TGF-β 信号通路会导致干细胞池的增殖。
