Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands.
Genesis. 2020 Sep;58(9):e23387. doi: 10.1002/dvg.23387. Epub 2020 Jul 9.
Wnt signal transduction controls tissue morphogenesis, maintenance and regeneration in all multicellular animals. In mammals, the WNT/CTNNB1 (Wnt/β-catenin) pathway controls cell proliferation and cell fate decisions before and after birth. It plays a critical role at multiple stages of embryonic development, but also governs stem cell maintenance and homeostasis in adult tissues. However, it remains challenging to monitor endogenous WNT/CTNNB1 signaling dynamics in vivo. Here, we report the generation and characterization of a new knock-in mouse strain that doubles as a fluorescent reporter and lineage tracing driver for WNT/CTNNB1 responsive cells. We introduced a multi-cistronic targeting cassette at the 3' end of the universal WNT/CTNNB1 target gene Axin2. The resulting knock-in allele expresses a bright fluorescent reporter (3xNLS-SGFP2) and a doxycycline-inducible driver for lineage tracing (rtTA3). We show that the Axin2 strain labels WNT/CTNNB1 responsive cells at multiple anatomical sites during different stages of embryonic and postnatal development. It faithfully reports the subtle and dynamic changes in physiological WNT/CTNNB1 signaling activity that occur in vivo. We expect this mouse strain to be a useful resource for biologists who want to track and trace the location and developmental fate of WNT/CTNNB1 responsive stem cells in different contexts.
Wnt 信号转导控制所有多细胞动物的组织形态发生、维持和再生。在哺乳动物中，WNT/CTNNB1（Wnt/β-连环蛋白）途径在出生前后控制细胞增殖和细胞命运决定。它在胚胎发育的多个阶段发挥着关键作用，但也控制着成年组织中干细胞的维持和内稳态。然而，在体内监测内源性 WNT/CTNNB1 信号转导动力学仍然具有挑战性。在这里，我们报告了一种新的敲入小鼠品系的产生和特征，该品系可兼作荧光报告基因和 WNT/CTNNB1 反应性细胞的谱系追踪驱动基因。我们在普遍的 WNT/CTNNB1 靶基因 Axin2 的 3'端引入了一个多顺反子靶向盒。由此产生的敲入等位基因表达一个明亮的荧光报告基因（3xNLS-SGFP2）和一个可诱导的谱系追踪驱动基因（rtTA3）。我们表明，Axin2 株在胚胎和出生后发育的不同阶段的多个解剖部位标记 WNT/CTNNB1 反应性细胞。它忠实地报告了体内发生的生理 WNT/CTNNB1 信号转导活性的细微和动态变化。我们期望这种小鼠品系成为生物学家的有用资源，他们希望在不同的背景下追踪和追踪 WNT/CTNNB1 反应性干细胞的位置和发育命运。
